Research in Your Backyard Developing Cures, Creating Jobs

Pharmaceutical Clinical Trials in

Minnesota Dots show locations of clinical trials in the state. An Overview

Clinical Trials in Minnesota St. Louis Park, Mercy Hospital in Coon Rapids, St. Mary’s Duluth Clinic in Duluth, St. Cloud • Biopharmaceutical research companies have Hospital in St. Cloud, St. Paul’s Heart Clinic conducted more than 2,400 clinical trials of new in St. Paul, University of Minnesota School of medicines since 1999 in collaboration with the Medicine in Minneapolis and the Mayo Clinic in state’s local research institutions, including the Rochester. Clinical Research Institute in Minneapolis and Plymouth, Twin Cities Clinical Research/Prism • The trials have been aimed at a wide array of Clinical Research in Brooklyn Center, Ridgeview diseases and medical conditions, ranging from Research in Chaska, Prism Clinical Research in the most debilitating chronic diseases, including St. Paul, MAPS Applied Research Center in Edina, cancer, pain, heart disease, obesity and diabetes, to Minnesotta Diet Research Center/Frestedt Inc. in bothersome allergies, sinusitis, chronic obstructive pulmonary disease (COPD), migraine headaches, pneumonia and rare diseases affecting small patient populations. “Clinical trials are required to get new medicines to the patients who need them. This is a • With so much clinical trial activity in the state, complicated business since completing a clinical widespread public awareness of trials is a challenge trial typically requires 6-7 years of effort. We must which led to the formation of a unique coalition— ensure the safety of each clinical trial participant the Minnesota Clinical Research Alliance to the extent possible while clearly measuring the (MCRA). effects of the new product. Enormous amounts of • MCRA provides important clinical research data are often collected and reviewed to evaluate education at a time when it is a challenge for the safety and efficacy of the product. Once biopharmaceutical companies and local research approved for the market, medicines continue to be collaborators to recruit volunteers and patients monitored by the companies that manufacture the often don’t know about trials of new drugs. products and the FDA to ensure their continued • Clinical trials in Minnesota have not only been safety and efficacy.” good for patients, but also the state’s economy and —Joy Frestedt, PhD, RAC, CCTI the advancement of science and overall patient President and CEO, Frestedt Incorporated health care.

2 PhRMA • Pharmaceutical Clinical Trials in Minnesota • In the words of Dr. Gary Berman of the Clinical Research Institute, an Alliance partner, the MCRA “Clinical research provides options for my has chosen “to put collaboration above competition patients who have conditions with very limited in the best interests of patients. We can all options. Not only do they have access to accomplish more by working together to promote compounds which are otherwise unavailable, the strength of research in Minnesota.” they also receive closer surveillance and • Many of the partners in the MCRA are heavily disease monitoring than they otherwise involved in the clinical testing of new medicines in would. Our clinical research program allows the state for a range of diseases, including infectious Kidney Specialists of Minnesota to provide our and respiratory conditions, cancer, asthma, migraine patients with treatments which far surpass the headaches, allergies and others. community standard of care.” • Some of the partners provide clinical research —Dr. Daniel Ries Co-Medical Director, Twin Cities Clinical Research expertise and sophisticated equipment that enable biopharmaceutical companies and their local collaborators to conduct trials of new medicines.

• To learn about the companies that make up the Alliance, visit the website www.mnclinicalresearch.org. MCRA—Making Patients Aware of Clinical Trials and Their Importance • The website address of each partner is provided and at each site, explanations in easy-to-read • The MCRA was launched a year ago to educate language are provided about the important work the public, elected officials and the media about the of each organization. On some sites, information importance of clinical research to patients and the is provided on trials of new medicines that are still health care system and the state’s economy. recruiting patients, making them potentially very important to some disease sufferers and their health • A collaborative effort of key elements of the care providers. Minnesota medical research community, MCRA is dedicated to explaining research all over the state • MCRA partners include Agility Research, “in understandable terms.” Courante Oncology, the Clinical Research Institute, Frestedt Inc., MAPS Applied Research Center • Alliance presentations, media meetings, opinion (MARC), MEDTOX Laboratories, the Minnesota pieces and materials stress the patient safety Center for Obesity, Metabolism & Endocrinology protections built into the clinical trial system and (MNCOME), Minnesota Diet Research Center how trials of new drugs and medical devices are (MDRC), Minnesota Gastroenterology, Prism helping to advance science and, ultimately, overall Clinical Research, The Greenlight Group, LLC, patient health care. Ridgeview Research and Twin Cities Clinical • MCRA also stresses the economic impact of clinical Research/Prism Clinical Research. research on a state that, in 2010, had 11 percent of • The BioBusiness Alliance of Minnesota and all of the clinical trials conducted in the United LifeScience Alley, another bioscience support States. Minnesota also boasts the second highest organization, collaborate with the Alliance as number of medical technology jobs in the nation. affiliates.

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 3 About Clinical Trials and Why the • Clinical trials account for 45 to 75 percent of the MCRA Mission is Important average $1.2 billion cost of developing one new biotechnology medicine and that’s an important • According to a 2007 survey by CenterWatch, a statistic considering that biopharmaceutical company that publishes information on clinical companies frequently hire local research trials, patient enrollment problems delay more than institutions, such as members of the MCRA and 70 percent of the tests of new medicines from one the University of Minnesota School of Medicine, to six months. Fewer than five percent of cancer to conduct the tests. patients participate in clinical trials. The educational • For some patients who are still seeking treatments efforts of the MCRA help to create more that are best for them, clinical trials can be a awareness and understanding of trials of new drugs potential therapeutic option to discuss with health and that gives Minnesota patients the opportunity care providers. to discuss becoming trial volunteers with their doctors. • Many medicines clinically tested in Minnesota and other states are cutting-edge biotechnology • Delays in clinical trials mean drug development drugs that have the strong potential to advance takes longer, costs more and patients have to wait science and patient health care. Biotech medicines for treatments they may desperately need. are derived from novel biological processes that • Clinical trials are conducted to help evaluate feature cells, genes and other living organisms. With the safety and effectiveness of new medicines biotechnology, we have the strong potential to and generate the data the Food and Drug develop safer and more effective treatments and we Administration needs to approve new treatments. A are improving our ability to predict, preempt and drug cannot be approved without adequate clinical prevent diseases. testing. • From the standpoint of patient safety in clinical • Clinical tests of new drugs are conducted in three trials, all tests of new medicines must be reviewed pre-approval phases and account for an average and approved by an Institutional Review Board of seven of the 10 to 15 years required today to (IRB)—an independent committee of health care research and develop a new treatment. Trials involve providers, social workers, statisticians, local patient thousands of volunteer patients and the generation advocates and others—to ensure trials are ethically of large volumes—sometimes tens of thousands of conducted and patient rights protected. Many IRBs pages—of technical and scientific data. exist right here in the state of Minnesota.

4 PhRMA • Pharmaceutical Clinical Trials in Minnesota The Importance of Clinical Trials

Since 1999, more than 2,400 clinical trials have been • Minnesota clinical research has been aimed at conducted or are being conducted in Minnesota. The cancer, diabetes, cardiovascular disease, HIV clinical trials have addressed many of the leading causes infection, mental and behavioral disorders, rare of death in the United States and in Minnesota, such as diseases and respiratory diseases. cancer, heart disease and diabetes. And they’ve targeted • Minnesota, in 2010, had the highest number of debilitating diseases that cause severe pain, such as psoria- investigational medical device and FDA pre-market sis, rheumatoid arthritis, and epilepsy. All of these condi- approvals of medical devices per capita. tions contribute to health care spending in Minnesota.

• In 2008, health care spending in Minnesota was $35.1 billion—for hospital care, physician services, Clinical Trials in Minnesota long term care, prescription drugs, dental services and other health care costs. All Clinical Trials Clinical Trials Still Recruiting

• Per capita spending on health care in Minnesota 2,468 391 was $6,720 in 2008, compared to the national

average of $7,166. Source: www.clinicaltrials.gov Note: Search criteria = Minnesota, Phase I, II, III; industry only. • In 2010, Minnesota was home to 11 percent of all Search performed 5/24/2012. clinical trials in the United States.

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 5 Clinical Trials in Minnesota Communities

Location cular O ther M ental C ancer C rohn’s A rthritis E pilepsy Diabetes I nfectious - C ardiovas R espiratory Kidney/ L iver

Brooklyn — — 2 2 — — — 2 — — — Center

Chaska 1 — 1 — — — — — — — 3

Duluth — 12 11 3 — — 3 — — — 3

Eagan 3 — 1 5 — — — — — — 1

Edina 6 6 2 2 — — — — — 2 4

Fridley 1 1 2 — — — 3 — — 3 9

Minneapolis — 63 43 13 — 4 15 21 10 23 —

Plymouth — — — — 4 — 5 — — 8 3

Rochester — 74 29 3 10 1 4 16 4 21 —

St. Louis Park — 18 1 — — — — — — — —

St. Cloud — 3 4 2 — 1 — — — — —

St. Paul 1 3 7 3 7 1 — — — — 3

Source: www.clinicaltrials.gov Note: Search criteria = Minnesota, Phase I, II, II; industry only. Search performed 5/24/2012. See Appendix for detailed information about these clinical trials. Disease columns will not match totals in the Appendix because some clinical trials are recruiting in more than one city.

6 PhRMA • Pharmaceutical Clinical Trials in Minnesota Clinical Trials in Minnesota

Clinical tests of new medicines are a vitally important part of the drug development and approval process—they ac- Clinical Trials In Minnesota count for 45 to 75 percent of the $1.2 billion average cost Clinical Trials Disease of developing a new drug and are conducted to determine Still Recruiting the safety and effectiveness of that treatment in patients. Arthritis 10 Cancer 132 Some trials are also conducted to compare existing treat- Cardiovascular Disease 52 ments and some are done to learn if a drug is appropriate for Crohn’s Disease/UlcerativeColitis/ a different patient population, such as children. Still others 27 are conducted to find ways to make existing approved drugs Gastrointestinal more effective and easier to use with fewer side effects. Diabetes 24 Epilepsy/Neurological Disorders 26 It’s essential that trials be conducted properly so that clini- Infectious Diseases 30 cians and drug reviewers can develop accurate assessments of the efficacy and safety of medicines used by patients. Kidney and Liver Disorders 17 The FDA is a vigilant regulatory agency and its pharma- Mental Illnesses 10 ceutical review officers are effective in detecting flawed Respiratory Diseases 19 information. Other Diseases 53

Questionable or confusing data can lead to lengthy delays in Source: www.clinicaltrials.gov Note: Search criteria = Minnesota, Phase I, II, III; industry only. Search performed product approval or outright FDA rejection of a new drug. 5/24/2012. Some clinical trials appear in more than one disease category.

Biopharmaceutical research companies are looking for tens of thousands of pages—are generated. In Minnesota, the best physicians and research institutions to help design biopharmaceutical companies arrange for trials of new and conduct their clinical trials to determine whether medicines to be conducted by Minnesota Clinical Re- medicines are safe and effective. Side effects must be well- search Alliance partners, the state’s well-respected univer- documented and a determination made as to whether sity medical schools and science centers, including Mayo they occur too often and are dangerous. Medical School and the University of Minnesota School of Medicine, local hospitals and other institutions. Accord- Clinical tests involve three phases prior to market re- ing to U.S. News and World Report, Mayo Medical School lease and thousands of volunteer patients and are often ranked 26th and the University of Minnesota Medical conducted at multiple sites around the country. Large School ranked 34th among this year’s top 100 research- volumes of technical and scientific data—sometimes oriented medical schools in the United States.

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 7 Arthritis, the most common cause of disability in the Currently, 52 cardiovascular disease clinical tests are seek- United States, affects about 50 million adults and 300,000 ing patients in Minnesota. The trials are being conducted children, according to the Arthritis Foundation. In Min- at the Minneapolis Heart Institute at Abbott Northwest- nesota, according to the Minnesota Department of Health ern Hospital in Minneapolis, MAPS Applied Research (MDH), approximately 995,000 adults or 26 percent of Center (MARC) in Edina, Minnesota Center for Minnesota adults have arthritis. Arthritis consists of more Obesity, Metabolism and Endocrinology (MNCOME) than 100 different diseases or conditions affecting the in Eagan, Prism Clinical Research and the St. Paul Heart joints, bones, muscles and other connective tissues. Clinic in St. Paul, Mercy Hospital in Coon Rapids, St. Cloud Hospital in St. Cloud and St. Mary’s Duluth There are 10 clinical trials recruiting patients in Minne- Clinic in Duluth. sota for arthritis, specifically rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, polymyalgia rheu- Crohn’s disease and Ulcerative colitis (inflamma- matica and bone loss associated with cancer treatment. tory bowel disease) affect 1.4 million Americans and are Trials are being conducted at St. Paul Rheumatology evenly split between the two, according to the Crohn’s in St. Paul and the Rheumatology Department at the and Colitis Foundation of America. Other gastrointesti- Mayo Clinic in Rochester, among others. nal disease medicine trials that are still recruiting patients in Minnesota are targeting chronic idiopathic constipa- Cancer, the second leading cause of death in the United tion, celiac disease, diabetes-related gastroparesis, irritable States, now afflicts nearly 12 million Americans, accord- bowel syndrome and eosinophilic esophagitis. ing to the National Cancer Institute. In Minnesota, more than 28,000 new cancer cases will be diagnosed this year Currently, 27 clinical tests are seeking patients in Minne- and 9,490 victims in the state will die, according to the sota for Crohn’s disease, ulcerative colitis, irritable bowel American Cancer Society. syndrome and other gastrointestinal disorders. The trials are being conducted at Ridgeview Research in Chaska, Currently, 132 clinical trials of new cancer medicines Minnesota Gastroenterology (MNGASTRO) in Plym- are recruiting patients in Minnesota. Biopharmaceutical outh, The Mayo Clinical in Rochester and Colon & companies are collaborating on the tests with such institu- Rectal Surgery Associates in Minneapolis. tions as the Mayo Clinical Cancer Center in Rochester, the Virginia Piper Cancer Institute at Abbott North- Diabetes affects more than 20 million Americans— western Hospital and the Masonic Cancer Center at about 8 percent of the U.S. population—and nearly the University of Minnesota in Minneapolis, the Park one-third are unaware they have the disease. Each year, Nicollet Clinical Fravenshuh Cancer Center in St. more than 26,000 Minnesotans are newly diagnosed with Louis Park, St. Mary’s Health System in Duluth, and the diabetes and it was the seventh leading cause of death in Regions Hospital Cancer Care Center in St. Paul. 2009, according to the Minnesota Department of Health.

Cardiovascular disease is the leading cause of death Currently, 24 diabetes clinical tests are seeking patients in the United States and in Minnesota. According to in Minnesota. The trials are being conducted at the Twin the American Heart Association, more than 82 million Cities Clinical Research/Prism Clinical Research in Americans are affected by these diseases. In Minnesota, Brooklyn Center, Mayo Clinic in Rochester, the Inter- in 2009, more than 9,000 residents died from some form national Diabetes Center in Minneapolis, Prism Clini- of cardiovascular disease, according to the Minnesota cal Research in St. Paul, Minnesota Center for Obesity, Department of Health. Metabolism and Endocrinology (MNCOME) in Eagan, and Radiant Research in Edina.

8 PhRMA • Pharmaceutical Clinical Trials in Minnesota Epilepsy affects nearly 3 million Americans, according athy, haptic veno-occlusive disease, cirrhosis, hepatic to the Epilepsy Foundation. The Epilepsy Foundation impairment and steatohepatitis and other conditions. Minnesota estimates that one in 26 people will develop There are 12 clinical trials for kidney diseases and 5 for liver the disease at some point in their life. Other neurologic diseases recruiting patients in Minnesota. Trials are underway disorders targeted by clinical trials that are still recruiting at DaVita Clinical Research and the University of Min- include migraines, chronic low back pain (internal disc nesota in Minneapolis, Twin Cities Clinical Research/ disruption, IDD), Parkinson’s disease, multiple sclerosis, Prism Clinical Research in Brooklyn Center, University cerebral palsy and muscular dystrophies. of Minnesota Medical Center in Fairview, Children’s Currently, there are 26 clinical trials recruiting patients Hospitals and Clinics of Minnesota in St. Paul, and in Minnesota for neurologic disorders. The trials are Rochester Methodist and Mayo Clinic in Rochester. underway at Abbott Northwestern Hospital and the Mental illness affects nearly 60 million Americans suffering University of Minnesota in Minneapolis, MAPS Applied from some form of the disease—from anxiety to depression Research Center (MARC) in Edina, St. Cloud Hospital to schizophrenia to eating disorders. In Minnesota, about in St. Cloud, Prism Clinical Research and Gilette Chil- 168,000 adults live with serious mental illness and about dren’s Specialty Health Care in St. Paul and Medical 56,000 children live with serious mental health conditions, Advanced Pain Specialists Applied Research Center according to the National Alliance on Mental Illness. in Edina, and the Minneapolis Clinic of Neurology in Golden Valley. Currently, 10 clinical trials are recruiting patients in Min- nesota. The trials are being conducted at the Mayo Clinic Infectious Diseases, both newly emerging and re- in Rochester, and in Minneapolis at the Minneapolis VA emerging, cause the death of at least 170,000 Americans Medical Center and the Ambulatory Research Center, each year, according to a 2008 report from Trust for Department of Psychiatry and the University of Minne- America’s Health. In 2010, 676 Minnesota residents died sota Medical Center. from infectious and parasitic diseases. Respiratory Disorders, such as asthma and chronic There are 30 clinical trials recruiting patients in Minne- obstructive pulmonary disease (COPD), are the third sota for infectious diseases, including, aspergillosis, herpes leading cause of death in the United States and in Min- zoster, influenza, meningococcal disease, onychomycosis, nesota. Asthma affects more than 23 million Americans candidiasis, HIV infection, urinary tract infections, intra- including 7 million children under the age of 18. The abdominal infections, Hepatitis B, Hepatitis C, Clostridium toll is also severe in Minnesota—in 2009, about 260,000 difficle infections, and athlete’s foot (tinea pedis). Trials are adults and 76,000 children had asthma, according to the being conducted at MNGASTRO (Minnesota Gastro- Minnesota Department of Health. COPD, which in- enterology) in St. Paul, the University of Minnesota, the cludes chronic bronchitis and emphysema, affects more Clinic42 and International Travel Clinic and the Hen- than 14 million Americans and in Minnesota 70,600 nepin County Medical Center in Minneapolis, and the adults over the age of 45 have COPD. Minnesota Clinical Study Center in Fridley. Currently, 19 clinical trials of new respiratory disease Kidney and Liver Diseases are the ninth and twelfth medicines are recruiting patients in Minnesota. Trials are leading causes of death in the United States and the being conducted at the University of Minnesota and the eighth and twelfth in Minnesota. Clinical trials recruit- Hennepin County Medical Center in Minneapolis, the ing patients in Minnesota are aimed at polycystic kidney Clinical Research Institute in Minneapolis and Plym- disease, renal impairment and insufficiency, amyloidosis, outh, and the Mayo Clinic in Rochester. hepatorenal syndrome type 1 and membranous nephrop-

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 9 Other diseases and medical conditions that are Currently, there are 52 clinical trials recruiting patients being targeted in Minnesota include: for these diseases. The trials are underway at the Clini- cal Research Institute in Minneapolis, Chu Vision and • abdominal aneurysms Minnesota Eye Consultants in Bloomington, the Mayo • allergic rhinitis Clinic in Rochester, the Orthopedic Surgery Center in • amyloidosis Bloomington and Edina, Minesota Diet Research Cen- • benign prostatic hyperplasia ter/Frestedt Inc. in St. Louis Park, Abbott Northwestern • glaucoma Hospital and the University of Minnesota in Minneapo- lis, Clinical Research Institute in Plymouth, and Chil- • hemophilia dren’s Hospitals and Clinics of Minnesota in St. Paul. • lupus • obesity Physicians and patients can find out about clinical trials being conducted across the state in collaboration with local institutions • overactive bladder by accessing www.clinicaltrials.gov, a database sponsored by • peanut allergy the National Institutes of Health. Information on medicines in • primary immunodeficiency diseases development is also available on www.phrma.org, the website • psoriasis of the Pharmaceutical Research and Manufacturers of America • sleep apnea (PhRMA).

10 PhRMA • Pharmaceutical Clinical Trials in Minnesota Minnesota – Clinical Trials of Biotechnology Drugs

Many of the medicines being tested in Minnesota are Many of the medicines in clinical testing at Minnesota cutting-edge biotechnology drugs. medical schools and research centers feature these tech- nologies. For example: America’s biopharmaceutical research companies are using biotechnology to develop hundreds of medicines • A genetically-modified virus-based vaccine to treat and vaccines today. And Minnesota is one of the states melanoma. where extensive new-generation research and develop- • A monoclonal antibody for the treatment of ment work is being done. cancer.

Through biotechnology, new ways are being developed • An antisense medicine for the treatment of cancer. to not only more effectively treat disease, but also to pre- dict, preempt, and prevent it. • A recombinant fusion protein to treat age-related macular degeneration and diabetic macular edema.

Biotechnology medicines are developed through biolog- • A therapeutic vaccine, designed to jump-start the ical processes using living cells or organisms, rather than immune system to fight disease, is in development traditional chemical synthesis, the mainstay of pharma- for lung cancer and melanoma. ceutical development for decades. • A fibrin sealant delivered with a novel device Such novel treatments use a variety of new approaches designed to inject the sealant directly into the to treat disease. For example, a monoclonal antibody is affected vertebral disc to potentially heal an a laboratory-made version of the naturally occurring internal disc disruption (IDD) which has caused immune system protein that binds to and neutralizes for- years of chronic low back pain. eign invaders. Interferons are proteins that interfere with the ability of a cell to reproduce. These are only a portion of the examples of new ways the nation’s biopharmaceutical companies and Minne- Antisense drugs, meanwhile, are medicines that interfere sota research institutions are working together to attack with the communication process that tells a cell to pro- disease. The biotechnology medicines and vaccines in duce an unwanted protein. In addition, nanotechnology development promise to push the frontiers of science is being used in biotechnology research to provide drug- and potentially bring more and better treatments to delivery systems, new treatments, and diagnostics. patients.

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 11 Conclusion

Biopharmaceutical companies’ close collaboration with What’s more, Minnesotans contemplating participa- clinicians and research institutions in Minnesota benefits tion in clinical trials, in consultation with their doctors, patients, the state’s economy, and the advancement of have a wide range of choices—nearly 400 tests of new science and patient care. Clinical trial work is good busi- medicines for many of the most debilitating diseases in ness for the state’s medical schools and clinical research America are underway in communities large and small centers and the medicines being tested are often cutting- all over the state and they need patient volunteers. edge cell and protein treatments with the potential to be safer and more effective than older chemical compound drugs.

12 PhRMA • Pharmaceutical Clinical Trials in Minnesota The Drug Discovery, Development and Approval Process

It takes 10-15 years on average for an experimental drug to travel from the lab to U.S. patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing. One of these five tested in people is approved.

Clinical Trials

Discovery/ Preclinical Testing Phase I Phase II Phase III FDA Phase IV

Years 6.5 1.5 2 3.5 1.5

20 to 100 100 to 500 1,000 to 5,000 Test Laboratory and

healthy patient patient at FDA Population animal studies volunteers volunteers volunteers Additional Review post- process/ marketing Confirm Assess safety, Evaluate approval testing

File IND at FDA Determine effectiveness, biological activity effective- required Purpose safety monitor adverse and formulations ness, look for File NDA/BLA by FDA and dosage ­reactions from side effects long-term use

5,000 Success compounds 5 1 Rate evaluated enter trials approved

The Drug Development and Approval Process The U.S. system of new drug approvals is Administration (FDA) to begin to test the drug hospitals. Physicians monitor patients closely to perhaps the most rigorous in the world. in people. The IND shows results of previous confirm efficacy and identify adverse events. experiments; how, where and by whom the It takes 10-15 years, on average, for an experi- New Drug Application (NDA)/Biologic new studies will be conducted; the chemical mental drug to travel from lab to U.S. patients, License Application (BLA). Following the structure of the compound; how it is thought according to the Tufts Center for the Study of completion of all three phases of clinical trials, to work in the body; any toxic effects found in Drug Development, based on drugs approved a company analyzes all of the data and files an the animal studies; and how the compound from 1994 through 1998. Only five in 5,000 NDA or BLA with FDA if the data successfully is manufactured. All clinical trials must be compounds that enter preclinical testing make demonstrate both safety and effectiveness. reviewed and approved by the Institutional it to human testing. And only one of those five The applications contain all of the scientific Review Board (IRB) where the trials will be is approved for sale. information that the company has gathered. conducted. Progress reports on clinical trials Applications typically run 100,000 pages or On average, it costs a company $1.2 billion, must be submitted at least annually to FDA and more. The average review time for the 21 new including the cost of failures, to get one new the IRB. therapeutics approved by the FDA in 2010 was medicine from the laboratory to U.S. patients, Clinical Trials, Phase I. These tests usu- 14.8 months. according to a 2007 study by the Tufts Center ally involve about 20 to 100 normal, healthy for the Study of Drug Development. Approval. Once FDA approves an NDA or volunteers. The tests study a drug’s safety BLA, the new medicine becomes available Once a new compound has been identified in profile, including the safe dosage range. The for physicians to prescribe. A company must the laboratory, medicines are developed as studies also determine how a drug is absorbed, continue to submit periodic reports to FDA, follows: distributed, metabolized, and excreted as well including any cases of adverse reactions and as the duration of its action. Preclinical Testing. A pharmaceutical com- appropriate quality-control records. For some pany conducts laboratory and animal studies Clinical Trials, Phase II. In this phase, medicines, FDA requires additional trials to show biological activity of the compound controlled trials of approximately 100 to 500 (Phase IV) to evaluate long-term effects. against the targeted disease, and the com- volunteer patients (people with the disease) Discovering and developing safe and effective pound is evaluated for safety. assess a drug’s effectiveness and determine new medicines is a long, difficult, and expensive the early side effect profile. Investigational New Drug Application (IND). process. PhRMA member companies invested After completing preclinical testing, a company Clinical Trials, Phase III. This phase usually an estimated $49.5 billion in research and files an IND with the U.S. Food and Drug involves 1,000 to 5,000 patients in clinics and development in 2011.

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 13 The Good News – Many Clinical Trials are Still Recruiting

There are 391 clinical trials of new medicines recruiting in Minnesota. These trials target many of the chronic and debilitating diseases affecting Americans and Minnesotans.

Clinical Trials in Minnesota Communities

Location O ther M ental C ancer C rohn’s A rthritis E pilepsy Diabetes I nfectious R espiratory Kidney/ L iver C ardiovascular

Brooklyn — — 2 2 — — — 2 — — — Center

Chaska 1 — 1 — — — — — — — 3

Duluth — 12 11 3 — — 3 — — — 3

Eagan 3 — 1 5 — — — — — — 1

Edina 6 6 2 2 — — — — — 2 4

Fridley 1 1 2 — — — 3 — — 3 9

Minneapolis — 63 43 13 — 4 15 21 10 23 —

Plymouth — — — — 4 — 5 — — 8 3

Rochester — 74 29 3 10 1 4 16 4 21 —

St. Louis Park — 18 1 — — — — — — — —

St. Cloud — 3 4 2 — 1 — — — — —

St. Paul 1 3 7 3 7 1 — — — — 3

Source: www.clinicaltrials.gov Note: Search criteria = Minnesota, Phase I, II, II; industry only. Search performed 5/24/2012. See Appendix for detailed information about these clinical trials. Disease columns will not match totals in the Appendix because some clinical trials are recruiting in more than one city.

14 PhRMA • Pharmaceutical Clinical Trials in Minnesota The Good News – Many Clinical Trials are Still Recruiting (continued) Arthritis—Institutions Hennepin County Medical Center, Minneapolis Conducting Clinical Trials MAPS Applied Research Center (MARC), Edina Mayo Clinic, Rochester Mayo Clinic, Rochester St. Paul Rheumatology, St. Paul Mercy Hospital, Coon Rapids Minneapolis Clinic of Neurology, Robbinsdale Cancer—Institutions Minneapolis Heart Institute Foundation-Abbott Conducting Clinical Trials Northwestern Hospital, Minneapolis Children’s Hospital & Clinics of Minnesota, Minneapolis VA Health Care System, Minneapolis Minneapolis Minnesota Center for Obesity, Metabolism and Community Clinical Oncology Program; Fridley, Endocrinology (MNCOME), Eagan Maplewood, St. Louis Park, St. Paul Prism Clinical Research, St. Paul Duluth Clinic Cancer Center, Duluth St. Cloud Hospital, St. Cloud Fairview Clinical Trials Services, Minneapolis St. Joseph’s Hospital, St. Paul Masonic Cancer Center-University of Minnesota St. Mary’s Hospital, Mayo Clinic, Rochester Physicians, Minneapolis St. Paul Heart Clinic, St. Paul Mayo Clinical Cancer Center, Rochester United Heart and Vascular Center, St. Paul Minnesota Oncology Associates; Burnsville, Coon University of Minnesota, Minneapolis Rapids, Edina, Fridley, Maplewood, Minneapolis, St. Paul, Waconia, Woodbury Diabetes—Institutions Minnesota Oncology Hematology, Minneapolis Conducting Clinical Trials North Memorial Hubert H. Humphrey Cancer Minnesota Center for Obesity, Metabolism and Center, Robbinsdale Endocrinology (MNCOME), Eagan Park Nicollet Clinic Fravenshuh Cancer Center, Prism Clinical Research, St. Paul St. Louis Park Twin Cities Clinical Research/Prism Clinical St. Luke’s Hospital Whiteside Institute for Clinical Research, Brooklyn Center Research, Duluth St. Mary’s Duluth Clinic Health System, Duluth Crohn’s Disease/Ulcerative Colitis—Institutions St. Mary’s Hospital-Mayo Clinic, Rochester Conducting Clinical Trials University of Minnesota Amplatz Children’s Hospital, Colon & Rectal Surgery Associates, Minneapolis Minneapolis Mayo Clinic, Rochester University of Minnesota Cancer Center, Minneapolis Minnesota Gastroenterology (MNGASTRO), Virginia Piper Cancer Institute-Abbott Northwestern Plymouth Hospital, Minneapolis Ridgeview Research, Chaska

Cardiovascular Disease—Institutions Epilepsy/Neurologic Disorders—Institutions Conducting Clinical Trials Conducting Clinical Trials Abbott Northwestern Hospital, Minneapolis Abbott Northwestern Hospital, Minneapolis DaVita Clinical Research, Minneapolis Clinical Research Institute, Minneapolis, Plymouth Essentia Health, Duluth Gilette Children’s Specialty Healthcare, St. Paul

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 15 The Good News – Many Clinical Trials are Still Recruiting (continued) MAPS Applied Research Center (MARC), Edina Mental Illness—Institutions Medical Advanced Pain Specialists Applied Research Conducting Clinical Trials Center, Edina Ambulatory Research Center, Department of Minneapolis Clinic of Neurology, Golden Valley Psychiatry, Minneapolis Minnesota Epilepsy Group, St. Paul Mayo Clinic, Rochester Prism Clinical Research, St. Paul Minneapolis VA Medical Center, Minneapolis St. Cloud Hospital, St. Cloud University of Minnesota Medical Center, Fairview University of Minnesota Medical Center, Fairview University of Minnesota, Minneapolis Respiratory Diseases—Institutions Conducting Clinical Trials Infectious Diseases—Institutions Clinical Research Institute, Minneapolis, Plymouth Conducting Clinical Trials Mayo Clinic, Rochester Clinic 42 and International Travel Clinic, Minneapolis University of Minnesota, Minneapolis Hennepin County Medical Center, Minneapolis HIV Program Hennepin County, Minneapolis Other Diseases—Institutions Minnesota Clinical Study Center, Fridley Conducting Clinical Trials Minnesota Gastroenterology (MNGASTRO), St. Paul Abbott Northwestern Hospital, Minneapolis University of Minnesota, Minneapolis Allergy & Asthma Specialists, Minneapolis Children’s Hospitals and Clinics of Minnesota, Kidney and Liver Disorders—Institutions St. Paul Conducting Clinical Trials Chu Vision, Bloomington Children’s Hospitals and Clinics of Minnesota, Clinical Research Center, Plymouth St. Paul Minnesota Diet Research Center (MDRC), Edina DaVita Clinical Research, Minneapolis Mayo Clinic Transplant Center, Rochester Mayo Clinic, Rochester Mayo Clinic, Rochester Prism Clinical Research, St. Paul Midwest Immunology, Plymouth Rochester Methodist Hospital at Mayo Clinic, Minnesota Center for Obesity, Metabolism and Rochester Endocrinology (MNCOME), Eagan Twin Cities Clinical Research/Prism Clinical Minnesota Clinical Study Center, Fridley Research, Brooklyn Center Frestedt Inc., Edina University of Minnesota Medical Center, Fairview Minnesota Eye Consultants, Bloomington University of Minnesota, Minneapolis Orthopedic Surgery Center, Bloomington, Edina University of Minnesota, Minneapolis

16 PhRMA • Pharmaceutical Clinical Trials in Minnesota Appendix

The clinical trials listed here involve tests that have not yet started recruiting patients or are just now seeking volunteers to participate. This information is potentially valuable to patients still seeking effective treatments for their chronic diseases. It provides a new therapeutic option to discuss with physicians.

Those interested in obtaining more information about certain trials can use the URL code listed for each test to log onto www.clinicaltrials.gov, the clinical tests database of the National Institutes of Health.

Arthritis Study 5: (10 clinical trials recruiting) Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis Study 1: http://ClinicalTrials.gov/show/NCT01583374 Long-Term Effectiveness And Safety Of CP-690,550 Study 6: For The Treatment Of Rheumatoid Arthritis A 3-arm Proof of Concept Study of AIN457, ACZ885 http://ClinicalTrials.gov/show/NCT00413699 or Corticosteroids in Patients With Polymyalgia Rheumatica Study 2: http://ClinicalTrials.gov/show/NCT01364389 Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy up to 2 Years of Secukinumab (AIN457) Study 7: in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Anti-TNFα Agents A Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic http://ClinicalTrials.gov/show/NCT01377012 Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy Study 3: http://ClinicalTrials.gov/show/NCT00925600 An Open Label Study for Patients With Rheumatoid Arthritis Study 8: http://ClinicalTrials.gov/show/NCT01215942 Efficacy at 24 Weeks and Long Term Safety, Tolerability and Efficacy up to 2 Years of Secukinumab (AIN457) in Study 4: Patients With Active Psoriatic Arthritis (PsA) A Study in Patients With Rheumatoid Arthritis http://ClinicalTrials.gov/show/NCT01392326 http://ClinicalTrials.gov/show/NCT01202773

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 17 Study 9: Study 6: Effect of Febuxostat on Joint Damage in An Open-Label, 2-Cohort, Multicenter, Study of E7080 Hyperuricemic Subjects With Early Gout in Previously Treated Subjects With Unresectable Stage http://ClinicalTrials.gov/show/NCT01078389 III or Stage IV Melanoma http://ClinicalTrials.gov/show/NCT01136967 Study 10: Study 7: Study of the Safety and Efficacy of Long-Term Rilonacept Treatment for the Prevention of Gout Flares Efficacy and Safety of Zoledronic Acid ( Every 4 Weeks http://ClinicalTrials.gov/show/NCT01459796 vs. Every 12 Weeks) in Patients With Documented Bone Metastases From Bone Cancer http://ClinicalTrials.gov/show/NCT00320710 Cancer Study 8: (132 clinical trials recruiting) Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive Study 1: B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 A Study of Pertuzumab in Addition to Chemotherapy Lymphoma Who Have Relapsed After Therapy and Are and Herceptin Trastuzumab) as Adjuvant Therapy in Not Eligible for Stem Cell Transplant Patients With HER2-Positive Primary Breast Cancer http://ClinicalTrials.gov/show/NCT01321541 http://ClinicalTrials.gov/show/NCT01358877 Study 9: Study 2: Efficacy & Safety Study of MORAb-004 to Treat Study of Denosumab as Adjuvant Treatment for Metastatic Colorectal Cancer Women With High Risk Early Breast Cancer Receiving http://ClinicalTrials.gov/show/NCT01507545 Neoadjuvant or Adjuvant Therapy (D-CARE) http://ClinicalTrials.gov/show/NCT01077154 Study 10: Panobinostat or Placebo With Bortezomib and Study 3: Dexamethasone in Patients With Relapsed Multiple A Study Of Inotuzumab Ozogamicin Plus Rituximab Myeloma For Relapsed/Refractory Aggressive Non-Hodgkin http://ClinicalTrials.gov/show/NCT01023308 Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy Study 11: http://ClinicalTrials.gov/show/NCT01232556 A Study of Ramucirumab in Patients With Gastric, Esophageal and Gastroesophageal Cancer Study 4: http://ClinicalTrials.gov/show/NCT01246960 A Study in Second Line Metastatic Colorectal Cancer http://ClinicalTrials.gov/show/NCT01183780 Study 12: The BEACON Study (Breast Cancer Outcomes With Study 5: NKTR-102) Study of E7080 in Subjects With Advanced Endometrial http://ClinicalTrials.gov/show/NCT01492101 Cancer and Disease Progression http://ClinicalTrials.gov/show/NCT01111461

18 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 13: Study 20: Myelodysplastic Syndromes (MDS) Event Free Survival Study of Patients With Advanced Non-Small Cell Lung With Iron Chelation Therapy Study Cancer http://ClinicalTrials.gov/show/NCT00940602 http://ClinicalTrials.gov/show/NCT00948675

Study 14: Study 21: Phase III Lucanix™ Vaccine Therapy in Advanced Immunotherapy Study for Surgically Resected Non-small Cell Lung Cancer (NSCLC) Following Pancreatic Cancer Front-line Chemotherapy http://ClinicalTrials.gov/show/NCT01072981 http://ClinicalTrials.gov/show/NCT00676507 Study 22: Study 15: An Open-label Study of GSK1120212 Compared With Study to Assess the Effectiveness of RCHOP With or Docetaxel in Stage IV KRAS-mutant Non-small Cell Without VELCADE in Previously Untreated Lung Cancer Non-Germinal Center B-Cell-like Diffuse Large B-Cell http://ClinicalTrials.gov/show/NCT01362296 Lymphoma Patients http://ClinicalTrials.gov/show/NCT00931918 Study 23: Study of Abiraterone Acetate in Patients With Study 16: Advanced Prostate Cancer Daily Everolimus in Combination With Trastuzumab http://ClinicalTrials.gov/show/NCT01217697 and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer Study 24: http://ClinicalTrials.gov/show/NCT01007942 Phase 1/2 Safety and Tolerability Study of SNS01-T in Relapsed or Refractory Multiple Myeloma Study 17: http://ClinicalTrials.gov/show/NCT01435720 A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) Study 25: in 131I-Refractory Differentiated Thyroid Cancer Combination Study of BMS-754807 and Erbitux® in http://ClinicalTrials.gov/show/NCT01321554 Subjects With Advanced or Metastatic Solid Tumors Study 18: http://ClinicalTrials.gov/show/NCT00908024 Chemotherapy and Radiation in Treating Patients With Study 26: Stage 3 Non-Small Cell Lung Cancer A Study for Patients With Pancreatic Cancer http://ClinicalTrials.gov/show/NCT00686959 http://ClinicalTrials.gov/show/NCT00839332 Study 19: Study 27: Study of BMS-754807 Combined With Letrozole or BMS-754807 Alone in Patients With Hormone Safety Study of Human Myeloid Progenitor Cells Receptor-Positive Breast Cancer and Resistance to (CLT-008) After Post-remission Chemotherapy for Non-Steroidal Aromatase Inhibitors Leukemia http://ClinicalTrials.gov/show/NCT01225172 http://ClinicalTrials.gov/show/NCT01297543

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 19 Study 28: Study 36: ch14.18 Pharmacokinetic Study in High-risk A Study of Onartuzumab (MetMAb) in Combination Neuroblastoma With Tarceva (Erlotinib) in Patients With Met http://ClinicalTrials.gov/show/NCT01592045 Diagnostic-Positive Non-Small Cell Lung Cancer Who Have Received Chemotherapy For Advanced or Study 29: Metastatic Disease (MetLung) http://ClinicalTrials.gov/show/NCT01456325 Study of ACE-011 to Determine Safe and Effective Dose of ACE-011 for the Treatment of Chemotherapy Study 37: Induced Anemia in Patients With Advanced Non-small Cell Lung Cancer A Study Comparing Treatment With http://ClinicalTrials.gov/show/NCT01284348 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Study 30: Receptor Positive Midgut Carcinoid Tumours http://ClinicalTrials.gov/show/NCT01578239 Multiple Ascending Dose of BMS-911543 http://ClinicalTrials.gov/show/NCT01236352 Study 38: Study 31: Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory A Study of IMC-3G3 in Soft Tissue Sarcoma Multiple Myeloma http://ClinicalTrials.gov/show/NCT01185964 http://ClinicalTrials.gov/show/NCT01478048

Study 32: Study 39: Study of Veltuzumab and 90Y-Epratuzumab in Trial of Gemcitabine/Carboplatin With or Without Relapsed/Refractory, Aggressive NHL Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects http://ClinicalTrials.gov/show/NCT01101581 With Previously Untreated Stage IV Squamous Non-Small-Cell Lung Cancer (NSCLC) Study 33: http://ClinicalTrials.gov/show/NCT01082549 Safety and Tolerability of HSC835 in Patients With Hematological Malignancies Study 40: http://ClinicalTrials.gov/show/NCT01474681 Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer Study 34: http://ClinicalTrials.gov/show/NCT01410565 Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Study 41: Tumors, Non-Hodgkin Lymphoma or Multiple Erlotinib Versus Oral Etoposide in Patients With Myeloma Recurrent or Refractory Pediatric Ependymoma http://ClinicalTrials.gov/show/NCT01177397 http://ClinicalTrials.gov/show/NCT01032070

Study 35: Study 42: A Phase 3 Study of Brentuximab Vedotin (SGN-35) in A Study of Chemotherapy and Ramucirumab vs. Patients at High Risk of Residual Hodgkin Lymphoma Chemotherapy Alone in Second Line Non-small Cell Following Stem Cell Transplant (The AETHERA Trial) Lung Cancer Patients Who Received Prior First Line http://ClinicalTrials.gov/show/NCT01100502 Platinum Based Chemotherapy http://ClinicalTrials.gov/show/NCT01168973

20 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 43: Study 51: Comparison of Docetaxel/Prednisone to Docetaxel/ A Study to Test the Ability of and Safety of Prednisone in Combination With OGX-011 in Men GSK2110183 in Treating Langerhans Cell Histiocytosis With Prostate Cancer http://ClinicalTrials.gov/show/NCT01395004 http://ClinicalTrials.gov/show/NCT01188187 Study 52: Study 44: Study of Ruxolitinib in Pancreatic Cancer Patients A Phase 1 Study of BMS-833923 (XL139) in Subjects http://ClinicalTrials.gov/show/NCT01423604 With Advanced or Metastatic Cancer http://ClinicalTrials.gov/show/NCT00670189 Study 53: Study of Safety and Tolerability of PCI-27483 in Study 45: Patients With Pancreatic Cancer Patients Receiving A Study to Evaluate New or Worsening Lens Treatment With Gemcitabine Opacifications in Subjects With Non-metastatic http://ClinicalTrials.gov/show/NCT01020006 Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy Study 54: http://ClinicalTrials.gov/show/NCT00925600 Study of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Study 46: Patients With B-Cell CLL (The ORIGIN Trial) Randomized Study of ON 01910.Na in Refractory http://ClinicalTrials.gov/show/NCT00910910 Myelodysplastic Syndrome Patients With Excess Blasts http://ClinicalTrials.gov/show/NCT01241500 Study 55: Phase 3 Study of Immunotherapy to Treat Advanced Study 47: Prostate Cancer Safety and Efficacy of Cryoablation for Metastatic http://ClinicalTrials.gov/show/NCT01057810 Lung Tumors http://ClinicalTrials.gov/show/NCT01307501 Study 56: A Study to Compare the Safety and Efficacy of an Study 48: Aromatase Inhibitor in Combination With Lapatinib, A Study in Patients With Acute Leukemia Trastuzumab or Both for the Treatment of Hormone http://ClinicalTrials.gov/show/NCT01214603 Receptor Positive, HER2+ Metastatic Breast Cancer http://ClinicalTrials.gov/show/NCT01160211 Study 49: Study 57: Efficacy and Safety of a Sunscreen Against Porfimer Sodium-induced Phototoxicity to Visible Light A Study of Avastin (Bevacizumab) in Combination http://ClinicalTrials.gov/show/NCT01256203 With Standard of Care Treatment in Patients With Lung Cancer Study 50: http://ClinicalTrials.gov/show/NCT01351415 GDC-0980 in Combination With a Fluoropyrimidine, Study 58: Oxaliplatin, and Bevacizumab in Patients With Advanced Solid Tumors A Phase I Study of GNKG186 in Patient With Relapsed http://ClinicalTrials.gov/show/NCT01332604 or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) http://ClinicalTrials.gov/show/NCT01035216

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 21 Study 59: Study 67: A Safety and Efficacy Study of Patients With Metastatic A Study to Determine the Efficacy and Safety of or Locally Advanced (Unresectable) Chondrosarcoma Lenalidomide in Patients With Mantle Cell NHL Who http://ClinicalTrials.gov/show/NCT01310816 Have Relapsed or Progressed After Treatment With Bortezomib or Are Refractory to Bortezomib. The Study 60: “EMERGE” Trial http://ClinicalTrials.gov/show/NCT00737529 Dasatinib Added to Gemcitabine for Subjects With Locally-advanced Pancreatic Cancer Study 68: http://ClinicalTrials.gov/show/NCT01395017 A Study of Ramucirumab (IMC-1121B) in Study 61: Combination With Eribulin Versus Eribulin Alone in Patients With Breast Cancer Study Evaluating the Safety and Tolerability of Weekly http://ClinicalTrials.gov/show/NCT01427933 Dosing of Oral MLN9708 in Adult Patients With Relapsed and Refractory Multiple Myeloma Study 69: http://ClinicalTrials.gov/show/NCT00963820 A Study of CDX-1127 in Patients With Select Solid Study 62: Tumor Types or Hematologic Cancers http://ClinicalTrials.gov/show/NCT01460134 A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Study 70: Mutation http://ClinicalTrials.gov/show/NCT01028222 Study of the Safety and Efficacy of MK-4827 Given With Temozolomide in Participants With Advanced Study 63: Cancer (MK-4827-014 AM1) http://ClinicalTrials.gov/show/NCT01294735 DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma Study 71: http://ClinicalTrials.gov/show/NCT01353222 A Phase 1b Study of AMG 386 in Combination With Study 64: Either Pegylated Liposomal Doxorubicin or Topotecan in Subjects With Advanced Recurrent Epithelial Study of Imprime PGG® in Combination With Ovarian Cancer Cetuximab in Subjects With Recurrent or Progressive http://ClinicalTrials.gov/show/NCT00770536 KRAS Wild Type Colorectal Cancer http://ClinicalTrials.gov/show/NCT01309126 Study 72: Study 65: Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma Study of Dovitinib Versus Sorafenib in Patients With (DLBCL) of RAD001 Versus Matching Placebo After Metastatic Renal Cell Carcinoma Patients Have Achieved Complete Response With http://ClinicalTrials.gov/show/NCT01223027 First-line Rituximab-chemotherapy http://ClinicalTrials.gov/show/NCT00790036 Study 66: Study of MK-3475 in Participants With Progressive Study 73: Locally Advanced or Metastatic Carcinoma, Melanoma, Safety Study of Human Myeloid Progenitor Cells or Non-small Cell Lung Carcinoma (CLT-008) After Cord Blood Transplant for (P07990/MK-3475-001 AM4) Hematologic Malignancy http://ClinicalTrials.gov/show/NCT01295827 http://ClinicalTrials.gov/show/NCT00891137

22 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 74: Study 81: Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase A Study of GA101 (RO5072759) in Combination With Inhibitor BAY80-6946 With Gemcitabine or Cisplatin Chemotherapy in Patients With Previously Untreated Plus Gemcitabine in Patients With Advanced Cancer Chronic Lymphocytic Leukemia (GALTON) http://ClinicalTrials.gov/show/NCT01460537 http://ClinicalTrials.gov/show/NCT01300247

Study 75: Study 82: Brentuximab Vedotin in Patients With CD30-positive Pharmacokinetic Drug-drug Interaction Study of Nonlymphomatous Malignancies Dovitinib (TKI258) in Patients With Advanced Solid http://ClinicalTrials.gov/show/NCT01461538 Tumors http://ClinicalTrials.gov/show/NCT01596647 Study 76: Study 83: Efficacy and Safety of Decitabine as Epigenetic Priming With Induction Chemotherapy in Pediatric Randomized Study to Compare CyberKnife to Acute Myelogenous Leukemia (AML) Subjects Surgical Resection In Stage I Non-small Cell Lung http://ClinicalTrials.gov/show/NCT01177540 Cancer http://ClinicalTrials.gov/show/NCT00840749 Study 77: Study 84: A Study of Obinutuzumab (RO5072759) in Combination With CHOP Chemotherapy Versus Dose Escalation Study of Safety and Tolerability of MabThera/Rituxan (Rituximab) With CHOP in AT-406 in Patients With Advanced Solid Tumors and Patients With CD20-Positive Diffuse Large B-Cell Lymphomas Lymphoma http://ClinicalTrials.gov/show/NCT01078649 http://ClinicalTrials.gov/show/NCT01287741 Study 85: Study 78: Study for Women With Platinum Resistant Ovarian Efficacy Study of REOLYSIN® in Combination With Cancer Evaluating EC145 in Combination With Doxil® Paclitaxel and Carboplatin in Platinum-Refractory (PROCEED) Head and Neck Cancers http://ClinicalTrials.gov/show/NCT01170650 http://ClinicalTrials.gov/show/NCT01166542 Study 86: Study 79: Researching Cardiovascular Events With a Weekly A Study of Pemetrexed & Carboplatin/Cisplatin or Incretin in Diabetes (REWIND) Gemcitabine & Carboplatin/Cisplatin With or Without http://ClinicalTrials.gov/show/NCT01394952 IMC-1121B in Patients Previously Untreated With Recurrent or Advanced Non-small Cell Lung Cancer Study 87: (NSCLC) Panitumumab Pediatric Study http://ClinicalTrials.gov/show/NCT01160744 http://ClinicalTrials.gov/show/NCT00658658 Study 80: Study 88: A Study of LY2875358 in Patients With Advanced Cancer Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer http://ClinicalTrials.gov/show/NCT01287546 http://ClinicalTrials.gov/show/NCT00807859

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 23 Study 89: Study 96: Pediatric Philadelphia Positive Acute Lymphoblastic Clinical Study of BYM338 for the Treatment of Leukemia Unintentional Weight Loss in Patients With Cancer of http://ClinicalTrials.gov/show/NCT01460160 the Lung or the Pancreas http://ClinicalTrials.gov/show/NCT01433263 Study 90: Study 97: A Study of Dalotuzumab + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + MK-8669 Combination Multiple Ascending Dose (MDX1105-01) Therapies in Participants With Advanced Cancer http://ClinicalTrials.gov/show/NCT00729664 (MK-0646-027 AM2) http://ClinicalTrials.gov/show/NCT01243762 Study 98: LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Study 91: Metastatic Breast Cancer Patients After One Prior A Study to Evaluate Pazopanib as an Adjuvant Herceptin Treatment Treatment for Localized Renal Cell Carcinoma (RCC) http://ClinicalTrials.gov/show/NCT01125566 http://ClinicalTrials.gov/show/NCT01235962 Study 99: Study 92: Phase Ib, Dose Escalation Study of Oral LDE225 in Phase I Clinical Study of CWP232291 in Acute Myeloid Combination With BKM120 in Patients With Advanced Leukemia Patients Solid Tumors http://ClinicalTrials.gov/show/NCT01398462 http://ClinicalTrials.gov/show/NCT01576666

Study 93: Study 100: Alisertib (MLN8237) or Investigator’s Choice in Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Relapsed/Refractory Peripheral T-Cell Patients With Metastatic Castration Resistant Prostate Lymphoma Cancer http://ClinicalTrials.gov/show/NCT01482962 http://ClinicalTrials.gov/show/NCT01308567

Study 94: Study 101: Study of Ramucirumab or IMC-18F1 With Docetaxel Study of a Drug [DCVax®-L] to Treat Newly or Docetaxel Alone as Second-Line Therapy in Diagnosed GBM Brain Cancer Participants With Bladder, Urethra, Ureter, or Renal http://ClinicalTrials.gov/show/NCT00045968 Pelvis Carcinoma http://ClinicalTrials.gov/show/NCT01282463 Study 102: A Study for Patients With Recurrent or Metastatic Study 95: Squamous Cell Head and Neck Cancer A Study of IMC-3G3 in Previously Treated Patients http://ClinicalTrials.gov/show/NCT01087970 With Unresectable and/or Metastatic Gastrointestinal Stromal Tumors Study 103: http://ClinicalTrials.gov/show/NCT01316263 Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) http://ClinicalTrials.gov/show/NCT01466179

24 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 104: Study 111: Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With A Study of Oral LGH447 in Patients With Relapsed Prednisone for the Treatment of Metastatic Castration and/or Refractory Multiple Myeloma Resistant Prostate Cancer http://ClinicalTrials.gov/show/NCT01456689 http://ClinicalTrials.gov/show/NCT01308580 Study 112: Study 105: A Study of LY2228820 in Patients With Advanced Phase 3 Study of ThermoDox With Radiofrequency Cancer Ablation (RFA) in Treatment of Hepatocellular http://ClinicalTrials.gov/show/NCT01393990 Carcinoma (HCC) http://ClinicalTrials.gov/show/NCT00617981 Study 113: Study of Palifosfamide-tris in Combination With Study 106: Doxorubicin in Patients With Front-line Metastatic Soft Phase-3 Double-Blind, Placebo-Controlled Tissue Sarcoma Study of Pomalidomide in Persons With http://ClinicalTrials.gov/show/NCT01168791 Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence Myelofibrosis and Study 114: RBC-Transfusion-Dependence Safety Study of Denosumab in Subjects With Recurrent http://ClinicalTrials.gov/show/NCT01178281 or Unresectable Giant Cell Tumor of Bone Study 107: http://ClinicalTrials.gov/show/NCT00680992 Study With SAR302503 in Patients With Polycythemia Study 115: Vera or Essential Thrombocythemia A Study of DMOT4039A in Patients With Unresectable http://ClinicalTrials.gov/show/NCT01420783 Pancreatic or Platinum-Resistant Ovarian Cancer Study 108: http://ClinicalTrials.gov/show/NCT01469793 Everolimus Plus Best Supportive Care Versus Placebo Study 116: Plus Best Supportive Care in the Treatment of Patients With Advanced Neuroendocrine Tumors (Gastro A Study of Oral Sapacitabine in Elderly Patients With Intestinal or Lung Origin) Newly Diagnosed Acute Myeloid Leukemia http://ClinicalTrials.gov/show/NCT01524783 http://ClinicalTrials.gov/show/NCT01303796

Study 109: Study 117: ADI-PEG 20 Versus Placebo in Subjects With Advanced A Study of Trastuzumab Emtansine in Comparison Hepatocellular Carcinoma Who Have Failed Prior With Treatment of Physician’s Choice in Patients With Systemic Therapy HER2-Positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy http://ClinicalTrials.gov/show/NCT01287585 (TH3RESA) Study 110: http://ClinicalTrials.gov/show/NCT01419197 Phase III Study of SAR302503 in Intermediate-2 and Study 118: High Risk Patients With Myelofibrosis Study of PF-05212384 (Also Known as PKI-587) http://ClinicalTrials.gov/show/NCT01437787 Administered Intravenously To Subjects With Solid Tumors http://ClinicalTrials.gov/show/NCT00940498

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 25 Study 119: Study 127: A Study to Evaluate the Efficacy and Safety of GS-6624 Bortezomib and Vorinostat in Treating Patients Combined With Gemcitabine for Metastatic Pancreatic With High-Risk Myelodysplastic Syndrome or Acute Adenocarcinoma Myeloid Leukemia http://ClinicalTrials.gov/show/NCT01472198 http://ClinicalTrials.gov/show/NCT00818649

Study 120: Study 128: Clinical Study of PM01183 in Patients With Acute Study of Gemcitabine and Abraxane to Treat Leukemia Potentially Operable Pancreatic Cancer http://ClinicalTrials.gov/show/NCT01314599 http://ClinicalTrials.gov/show/NCT01298011

Study 121: Study 129: Trial of Nelarabine, Etoposide and Cyclophosphamide Bortezomib, Vorinostat and Dexamethasone for in Relapsed T-cell ALL and T-cell LL Relapsed/Refractory Acute Lymphoblastic Leukemia http://ClinicalTrials.gov/show/NCT00981799 (ALL) http://ClinicalTrials.gov/show/NCT01312818 Study 122: Study 130: A Study Of Panobinostat In Children With Refractory Hematologic Malignancies A Study With Neoadjuvant mFOLFOX7 Plus http://ClinicalTrials.gov/show/NCT01321346 Cetuximab to Determine the Surgical Conversion Rate for Unresectable Colorectal Cancer With Metastases Study 123: Confined to the Liver http://ClinicalTrials.gov/show/NCT00803647 A Phase I Study of AC220 for Children With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Study 131: Myelogenous Leukemia http://ClinicalTrials.gov/show/NCT01411267 Erlotinib for Chemoprevention in Trisomy 7 Positive Primary Sclerosing Cholangitis (PSC) Study 124: http://ClinicalTrials.gov/show/NCT00955149 Clofarabine With Cytarabine for Patients With Minimal Study 132: Residual Disease Positive Leukemia http://ClinicalTrials.gov/show/NCT01158885 Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma Study 125: http://ClinicalTrials.gov/show/NCT01506596 BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma Cardiovascular Disease http://ClinicalTrials.gov/show/NCT01034631 (52 clinical trials recruiting)

Study 126: Study 1: Lenalidomide and Low-Dose Dexamethasone in RED-HF™ Trial—Reduction of Events With Patients With Previously Treated Multiple Myeloma and Darbepoetin Alfa in Heart Failure Trial Kidney Dysfunction http://ClinicalTrials.gov/show/NCT00358215 http://ClinicalTrials.gov/show/NCT00790842

26 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 2: Study 10: Cardiovascular Risk Reduction Study (Reduction in Evaluation of the WATCHMAN LAA Closure Device Recurrent Major CV Disease Events) in Patients With Atrial Fibrillation Versus Long Term http://ClinicalTrials.gov/show/NCT01327846 Warfarin Therapy http://ClinicalTrials.gov/show/NCT01182441 Study 3: Study 11: A Study of Dalcetrapib in Patients With Stable Coronary Heart Disease, With Coronary Heart Disease Evaluation of Cardiovascular Outcomes in Patients Risk Equivalents or at Elevated Risk for Cardiovascular With Type 2 Diabetes After Acute Coronary Syndrome Disease During Treatment With AVE0010 (Lixisenatide) http://ClinicalTrials.gov/show/NCT01516541 http://ClinicalTrials.gov/show/NCT01147250

Study 4: Study 12: Prevention of Cardiovascular Events (eg, Death From Renal Denervation in Patients With Uncontrolled Heart or Vascular Disease, Heart Attack, or Stroke) Hypertension (SYMPLICITY HTN-3) in Patients With Prior Heart Attack Using Ticagrelor http://ClinicalTrials.gov/show/NCT01418261 Compared to Placebo on a Background of Aspirin http://ClinicalTrials.gov/show/NCT01225562 Study 13: Effect of Otamixaban Versus Unfractionated Heparin Study 5: + Eptifibatide in Patients With Unstable Angina/Non Cardiovascular Safety of Febuxostat and Allopurinol in ST Elevation Myocardial Infarction Undergoing Early Patients With Gout and Cardiovascular Comorbidities Invasive Strategy http://ClinicalTrials.gov/show/NCT01101035 http://ClinicalTrials.gov/show/NCT01076764

Study 6: Study 14: Cardiovascular Outcomes Study of Alogliptin in Determining the Feasibility of Spinal Cord Subjects With Type 2 Diabetes and Acute Coronary Neuromodulation for the Treatment of Chronic Heart Syndrome Failure http://ClinicalTrials.gov/show/NCT00968708 http://ClinicalTrials.gov/show/NCT01112579

Study 7: Study 15: Ranolazine for Incomplete Vessel Revascularization An Efficacy and Safety Study of Ixmyelocel-T in Post-Percutaneous Coronary Intervention (PCI) Patients With Critical Limb Ischemia (CLI) http://ClinicalTrials.gov/show/NCT01442038 http://ClinicalTrials.gov/show/NCT01483898

Study 8: Study 16: The PARTNER II Trial: Placement of AoRTic Gene Therapy for the Treatment of Chronic Stable TraNscathetER Valves Angina http://ClinicalTrials.gov/show/NCT01314313 http://ClinicalTrials.gov/show/NCT01002495

Study 9: A Study of RO4905417 in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery http://ClinicalTrials.gov/show/NCT01245634

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 27 Study 17: Study 24: A Randomized, Concurrent Controlled Trial to Efficacy and Safety of Targeted Intramyocardial Assess the Safety and Effectiveness of the Separator Delivery of Auto CD34+ Stem Cells for Improving 3D as a Component of the Penumbra System in the Exercise Capacity in Subjects With Refractory Angina Revascularization of Large Vessel Occlusion in Acute http://ClinicalTrials.gov/show/NCT01508910 Ischemic Stroke http://ClinicalTrials.gov/show/NCT01584609 Study 25: ACT-293987 in Pulmonary Arterial Hypertension Study 18: http://ClinicalTrials.gov/show/NCT01106014 Safety and Feasibility Trial of Autologous Adipose Derived Stem Cells in the Treatment of Chronic Study 26: Myocardial Ischemia Evaluate the Safety and Efficacy of OAS in Treating http://ClinicalTrials.gov/show/NCT01556022 Severely Calcified Coronary Lesions Study 19: http://ClinicalTrials.gov/show/NCT01092416 Safety Study of Allogeneic Mesenchymal Precursor Study 27: Cells (MPCs) in Subjects With Recent Acute Myocardial Infarction AngelMed for Early Recognition and Treatment of STEMI http://ClinicalTrials.gov/show/NCT00555828 http://ClinicalTrials.gov/show/NCT00781118 Study 20: Study 28: Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) CANARY: Coronary Assessment by Near-infrared of Atherosclerotic Rupture-prone Yellow http://ClinicalTrials.gov/show/NCT00683696 http://ClinicalTrials.gov/show/NCT01268319 Study 21: Study 29: Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced http://ClinicalTrials.gov/show/NCT01064440 Angioedema Study 22: http://ClinicalTrials.gov/show/NCT01343823 VIVID—Valvular and Ventricular Improvement Via Study 30: iCoapsys Delivery—Feasibility Study Study to Evaluate the Safety and Efficacy of JVS-100 http://ClinicalTrials.gov/show/NCT00512005 Administered to Adults With Critical Limb Ischemia Study 23: http://ClinicalTrials.gov/show/NCT01410331 Left Atrial Pressure Monitoring to Optimize Heart Study 31: Failure Therapy A Study Assessing The Pharmacokinetics, http://ClinicalTrials.gov/show/NCT01121107 Pharmacodynamics, Safety And Tolerability Of Subcutaneous Bolus And Subcutaneous Infusion Of Cenderitide In Patients With Chronic Heart Failure With Volume Overload (HF) http://ClinicalTrials.gov/show/NCT01316432

28 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 32: Study 40: Addition of UT-15C SR to Pulmonary Arterial An Extension Study for Patients Who Participated in Hypertension Patients Currently Receiving Tyvaso® the CAMN107X2201 Study http://ClinicalTrials.gov/show/NCT01477333 http://ClinicalTrials.gov/show/NCT01531270

Study 33: Study 41: Post-Myocardial Infarction Remodeling Prevention Study to Evaluate TRV120027 on Renal Therapy Pharmacodynamics in Patients With Heart Failure and http://ClinicalTrials.gov/show/NCT01213251 Renal Dysfunction http://ClinicalTrials.gov/show/NCT01444872 Study 34: Study 42: Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) C-Pulse IDE Feasibility Study- A Heart Assist System http://ClinicalTrials.gov/show/NCT01394952 http://ClinicalTrials.gov/show/NCT00815880

Study 35: Study 43: Safety and Efficacy Study of the Sorin 3D Annuloplasty Open Label Study of Long Term Evaluation Against Ring For Mitral Repair LDL-C Trial (OSLER) http://ClinicalTrials.gov/show/NCT00567853 http://ClinicalTrials.gov/show/NCT01439880

Study 36: Study 44: A Study of Dalcetrapib in Patients Hospitalized For An Assessment of Patients With PAH Right Ventricular Acute Coronary Syndrome (Dal-ACUTE) Volume http://ClinicalTrials.gov/show/NCT01323153 http://ClinicalTrials.gov/show/NCT01557582

Study 37: Study 45: Efficacy and Safety of Extended Release (ER) Niacin/ A Study of RO4905417 in Patients With Non Laropiprant When Added to Ongoing Lipid-Modifying ST-Elevation Myocardial Infarction (Non-STEMI) Therapy in Patients With High Cholesterol or Undergoing Percutaneous Coronary Intervention Abnormal Lipid Levels (Protocol MK-0524A-133 AM1) http://ClinicalTrials.gov/show/NCT01327183 http://ClinicalTrials.gov/show/NCT01274559 Study 46: Study 38: Extension to QTI571A2301 to Evaluate the Long-term AMR-001 Versus Placebo Post ST Segment Elevation Safety, Tolerability and Efficacy of Imatinib in Severe Myocardial Infarction Pulmonary Arterial Hypertension http://ClinicalTrials.gov/show/NCT01495364 http://ClinicalTrials.gov/show/NCT01117987

Study 39: Study 47: Safety, Tolerability, Pharmacokinetics and Acute Venous Thrombosis: Thrombus Removal With Pharmacodynamics Response of Vasomera (PB1046) Adjunctive Catheter-Directed Thrombolysis Injection Following a Single Subcutaneous Dose in http://ClinicalTrials.gov/show/NCT00790335 Subjects With Stage 1 or 2 Essential Hypertension http://ClinicalTrials.gov/show/NCT01523067

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 29 Study 48: Study 4: The Evaluation of VAD InterVEntion Before Inotropic A Study With Aleglitazar in Patients With a Recent Therapy Acute Coronary Syndrome and Type 2 Diabetes http://ClinicalTrials.gov/show/NCT01369407 Mellitus http://ClinicalTrials.gov/show/NCT01042769 Study 49: Study 5: Lp-PLA2, Progenitor Cells and Coronary Atherosclerosis in Humans AIM III Sitagliptin Cardiovascular Outcome Study http://ClinicalTrials.gov/show/NCT01067339 (0431-082 AM1) http://ClinicalTrials.gov/show/NCT00790205 Study 50: Study 6: Insulin Resistance Intervention After Stroke Trial http://ClinicalTrials.gov/show/NCT00091949 Cardiovascular Outcomes Study of Alogliptin in Subjects With Type 2 Diabetes and Acute Coronary Study 51: Syndrome http://ClinicalTrials.gov/show/NCT00968708 A Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function Study 7: http://ClinicalTrials.gov/show/NCT01522950 Comparison of a New Formulation of Insulin Glargine Study 52: With Lantus in Patients With Type 2 Diabetes Mellitus on Basal Plus Mealtime Insulin Clarification of Optimal Anticoagulation Through http://ClinicalTrials.gov/show/NCT01499082 Genetics http://ClinicalTrials.gov/show/NCT00839657 Study 8: Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes on Basal Diabetes Insulin With Oral Antidiabetic Therapy (24 clinical trials recruiting) http://ClinicalTrials.gov/show/NCT01499095

Study 1: Study 9: Exenatide Study of Cardiovascular Event Lowering A 6 Week Pharmacokinetics, Pharmacodynamics, Trial (EXSCEL): A Trial To Evaluate Cardiovascular Safety and Tolerability of GK1-399 in Type 2 Diabetes Outcomes After Treatment With Exenatide Once http://ClinicalTrials.gov/show/NCT01474083 Weekly In Patients With Type 2 Diabetes Mellitus http://ClinicalTrials.gov/show/NCT01144338 Study 10: CAROLINA: Cardiovascular Outcome Study of Study 2: Linagliptin Versus Glimepiride in Patients With Type 2 BI 10773 Cardiovascular Outcome Event Trial in Type 2 Diabetes Diabetes Mellitus Patients. http://ClinicalTrials.gov/show/NCT01243424 http://ClinicalTrials.gov/show/NCT01131676

Study 3: A Study in Patients With Type I Diabetes Mellitus http://ClinicalTrials.gov/show/NCT01454284

30 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 11: Study 18: A Study of BMS-512148 (Dapagliflozin) in Patients Study to Assess Pharmacodynamics of RM-131 in With Type 2 Diabetes With Inadequately Controlled Patients With Diabetic Gastroparesis Hypertension on an Angiotensin-Converting Enzyme http://ClinicalTrials.gov/show/NCT01394055 Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) Study 19: http://ClinicalTrials.gov/show/NCT01137474 Pharmacokinetic Profile of Two Formulations of PB1023 Following Single Subcutaneous Injection in Study 12: Subjects With Type 2 Diabetes Mellitus A Multicenter, Randomized, Double-blind, http://ClinicalTrials.gov/show/NCT01427257 Placebo-controlled Study to Evaluate the Efficacy and Safety of Saxagliptin (BMS-477118) in Combination Study 20: With Metformin IR or Metformin XR in Pediatric Patients With Type 2 Diabetes Who Have Inadequate A Study to Determine the Safety, Tolerability, and Glycemic Control on Metformin Alone Effects of GSK2374697 in Healthy Volunteers http://ClinicalTrials.gov/show/NCT01434186 http://ClinicalTrials.gov/show/NCT01545570

Study 13: Study 21: A Study in Participants With Type 2 Diabetes Mellitus Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes http://ClinicalTrials.gov/show/NCT01468987 http://ClinicalTrials.gov/show/NCT01351675 Study 14: Study 22: A Trial Comparing the Efficacy of Insulin Degludec With Insulin Glargine on Glycaemic Control Using Comparison of Technosphere Insulin Versus Continuous Glucose Monitoring in Patients With Type Technosphere Powder (Placebo) in Insulin-Naive 1 Diabetes Subjects With Type 2 Diabetes Mellitus http://ClinicalTrials.gov/show/NCT01569841 http://ClinicalTrials.gov/show/NCT01451398

Study 15: Study 23: Welchol as Add-on to Pioglitazone Therapy for Type 2 Pharmacokinetic, Safety/Tolerability Study of a Single Diabetes Mellitus SC Dose of PB1023 Injection in Subjects With Normal and Impaired Renal Function http://ClinicalTrials.gov/show/NCT00789750 http://ClinicalTrials.gov/show/NCT01478399 Study 16: Study 24: Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Insulin Resistance Intervention After Stroke Trial Mellitus Over a 24-week Treatment Period http://ClinicalTrials.gov/show/NCT00091949 http://ClinicalTrials.gov/show/NCT01445951

Study 17: Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) http://ClinicalTrials.gov/show/NCT01394952

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 31 Crohn’s Disease/Ulcerative Study 7: Colitis/Gastrointestinal Induction and Maintenance Study of BMS-936557 Disorders Patients With Moderate to Severe Ulcerative Colitis http://ClinicalTrials.gov/show/NCT01294410 (27 clinical trials recruiting) Study 8: Study 1: A Study in Healthy Volunteers to Evaluate Effects of A Multicenter Trial Comparing REMICADE Pre-Medication or Slow Dose Titration on Flushing (Infliximab) and Placebo in the Prevention of and Gastrointestinal Events Recurrence in Crohn’s Disease (CD) Patients http://ClinicalTrials.gov/show/NCT01568112 Undergoing Surgical Resection Who Are at an Increased Risk of Recurrence Study 9: http://ClinicalTrials.gov/show/NCT01190839 Study to Evaluate the Long-term Safety of rhuMAb Beta7 in Patients With Moderate to Severe Ulcerative Study 2: Colitis Effect of TU-100 on Rectal Compliance, Rectal http://ClinicalTrials.gov/show/NCT01461317 Sensation and Small Bowel and Colonic Transit in Females With Constipation Study 10: http://ClinicalTrials.gov/show/NCT01139216 B0151003 Open-Label Extension Study http://ClinicalTrials.gov/show/NCT01345318 Study 3: The Plecanatide Chronic Idiopathic Constipation (CIC) Study 11: Study GSK1605786A in the Maintenance of Remission in http://ClinicalTrials.gov/show/NCT01429987 Subjects With Crohn’s Disease http://ClinicalTrials.gov/show/NCT01316939 Study 4: A Double-blind Placebo-controlled Study to Evaluate Study 12: Larazotide Acetate for the Treatment of Celiac Disease A Study to Evaluate the Safety and Efficacy of http://ClinicalTrials.gov/show/NCT01396213 Ustekinumab in Patients With Moderately to Severely Active Crohn’s Disease Who Have Failed or Are Study 5: Intolerant to Tumor Necrosis Factor (TNF) Antagonist Effect of TU-100 in Patients With Functional Therapy (UNITI-1) Constipation http://ClinicalTrials.gov/show/NCT01369329 http://ClinicalTrials.gov/show/NCT01348152 Study 13: Study 6: Safety and Pharmacokinetics of MMX Mesalamine in Study To Test Whether PF-00547659 Is Safe And Children and Adolescents With Ulcerative Colitis Improves Disease Symptoms In Patients With http://ClinicalTrials.gov/show/NCT01130844 Crohn’s Disease That Have Not Responded To Other Treatments. Study 14: http://ClinicalTrials.gov/show/NCT01276509 Safety and Maintenance Study of Entocort for Children With Crohn’s Disease http://ClinicalTrials.gov/show/NCT01453946

32 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 15: Study 23: Study to Assess Pharmacodynamics of RM-131 in Safety Study of Entocort for Children With Crohn’s Patients With Diabetic Gastroparesis Disease http://ClinicalTrials.gov/show/NCT01394055 http://ClinicalTrials.gov/show/NCT01444092

Study 16: Study 24: A Safety and Efficacy Study of BLI-1300 Ointment in Open-Label Extension Study of GSK1605786A Symptomatic Perianal Crohn’s Disease http://ClinicalTrials.gov/show/NCT01318993 http://ClinicalTrials.gov/show/NCT01442363 Study 25 Study 17: A Study To Assess The Efficacy And Safety Of Evaluate the Efficacy and Safety of rhuMAb Beta7 in PF-04236921 In Subjects With Crohn’s Disease Who Patients With Moderate to Severe Ulcerative Colitis Failed Anti-TNF Therapy http://ClinicalTrials.gov/show/NCT01336465 http://ClinicalTrials.gov/show/NCT01287897

Study 18: Study 26: A Study to Investigate the Efficacy and Safety of Trial of Montelukast in Eosinophilic Esophagitis GSK1605786A in the Treatment of Subjects With http://ClinicalTrials.gov/show/NCT00511316 Moderately-to-Severely Active Crohn’s Disease http://ClinicalTrials.gov/show/NCT01277666 Study 27: A Placebo-Controlled Trial of Pregabalin (Lyrica) for Study 19: Irritable Bowel Syndrome Study of Asimadoline to Treat Diarrhea-Predominant http://ClinicalTrials.gov/show/NCT00977197 Irritable Bowel Syndrome (D-IBS) http://ClinicalTrials.gov/show/NCT01100684 Epilepsy/Neurologic Disorders Study 20: (26 clinical trials recruiting) A Phase 2 Study to Evaluate Pharmacodynamics of YKP10811 in Patients With Chronic or Functional Study 1: Constipation http://ClinicalTrials.gov/show/NCT01523184 Premium Migraine Trial http://ClinicalTrials.gov/show/NCT00355056 Study 21: Study 2: Efficacy, Safety, and Tolerability of JNJ-27018966 in the Treatment of Patients With Diarrhea-Predominant Trial to Demonstrate the Efficacy and Safety of Irritable Bowel Syndrome (Protocol Conversion to Lacosamide Monotherapy for JNJ-27018966IBS3001) Partial-onset Seizures http://ClinicalTrials.gov/show/NCT01553591 http://ClinicalTrials.gov/show/NCT00520741

Study 22: Study 3: A Study To Monitor Long-Term Treatment With Safety and Efficacy Study of SYN115 in Parkinson’s PF-00547659 Patients Using Levodopa to Treat End of Dose http://ClinicalTrials.gov/show/NCT01298492 Wearing Off http://ClinicalTrials.gov/show/NCT01283594

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 33 Study 4: Study 12: Study to Assess the Safety and Tolerability of A Study of Ocrelizumab in Comparison With Intravenous Carbamazepine in Adults With Epilepsy Interferon Beta-1a (Rebif) in Patients With Relapsing http://ClinicalTrials.gov/show/NCT01128959 Multiple Sclerosis http://ClinicalTrials.gov/show/NCT01247324 Study 5: Study 13: Study of Ataluren for Previously Treated Patients With nmDBMD in the US Brivaracetam Efficacy and Safety Study in Subjects http://ClinicalTrials.gov/show/NCT01247207 With Partial Onset Seizures http://ClinicalTrials.gov/show/NCT01261325 Study 6: Study 14: A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With A Multicenter, Open-Label Study To Investigate The SPMS Safety And Pharmacokinetics Of Lacosamide In http://ClinicalTrials.gov/show/NCT01416181 Children With Partial Seizures http://ClinicalTrials.gov/show/NCT00938431 Study 7: Study 15: Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and Its N-acetyl Metabolite Study to Evaluate Eye Function in Patients Taking http://ClinicalTrials.gov/show/NCT01480609 Linezolid for Two Months or Greater http://ClinicalTrials.gov/show/NCT00359632 Study 8: Study 16: Treatment of Symptomatic Lumbar Internal Disc Disruption (IDD) With the Biostat® System Safety Study of 3 mg/mL Baclofen Injection http://ClinicalTrials.gov/show/NCT01011816 (Intrathecal) Using A Programmable Pump http://ClinicalTrials.gov/show/NCT01520545 Study 9: Study 17: Dysport® Pediatric Lower Limb Spasticity Study http://ClinicalTrials.gov/show/NCT01249417 Eslicarbazepine Acetate Monotherapy Long Term Study Study 10: http://ClinicalTrials.gov/show/NCT00910247 Study to Evaluate the Safety and Effectiveness of Study 18: USL261 in Patients With Seizure Clusters http://ClinicalTrials.gov/show/NCT01390220 Brivaracetam Safety and Efficacy Follow-up Study in Subjects With Partial Onset Seizures Study 11: http://ClinicalTrials.gov/show/NCT01339559 Open-label, Pharmacokinetic, Safety and Efficacy Study 19: Study of Adjunctive Brivaracetam in Children With Epilepsy Safety and Efficacy of Eslicarbazepine Acetate http://ClinicalTrials.gov/show/NCT00422422 Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs http://ClinicalTrials.gov/show/NCT01091662

34 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 20: Infectious Diseases A Placebo- and Active Controlled Study of Preladenant (30 clinical trials recruiting) in Subjects With Moderate to Severe Parkinson’s Disease (Study P04938 AM5) Study 1: http://ClinicalTrials.gov/show/NCT01155466 Isavuconazole (BAL8557) for Primary Treatment of Study 21: Invasive Aspergillosis http://ClinicalTrials.gov/show/NCT00412893 Efficacy and Safety of YKP3089 in Subjects With Treatment Resistant Partial Onset Seizures Study 2: http://ClinicalTrials.gov/show/NCT01397968 A Study to Evaluate the Safety and Efficacy of Study 22: Inactivated Varicella-zoster Vaccine (VZV) as a Preventative Treatment for Herpes Zoster (HZ) and A Placebo- and Active-Controlled Study of Preladenant HZ-related Complications in Adult Participants With in Early Parkinson’s Disease (P05664 AM5) Solid Tumor or Hematologic Malignancy (V212-011 http://ClinicalTrials.gov/show/NCT01155479 AM1) http://ClinicalTrials.gov/show/NCT01254630 Study 23: Dysport® Pediatric Lower Limb Spasticity Follow-on Study 3: Study A Study of Intravenously Administered Tamiflu http://ClinicalTrials.gov/show/NCT01251380 (Oseltamivir) in Patients Over 13 Years of Age With Influenza Study 24: http://ClinicalTrials.gov/show/NCT01050257 A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD) Study 4: http://ClinicalTrials.gov/show/NCT01462292 A Clinical Trial to Study the Safety, Tolerance and Immunogenic Response to MCV4, Tdap and rLP2086 Study 25: Vaccine When Given at the Same Time to Children Safety and Efficacy of Gabapentin for Neuropathic Between the Ages of 10 Through 12 Years of Age Pain in Fabry Disease http://ClinicalTrials.gov/show/NCT01461980 http://ClinicalTrials.gov/show/NCT01588314 Study 5: Study 26: Safety and Efficacy of Luliconazole Solution, 10% in Apnex Clinical Study of the Hypoglossal Nerve Subjects With Mild to Moderate Onychomycosis Stimulation (HGNS®) System to Treat Obstructive http://ClinicalTrials.gov/show/NCT01431820 Sleep Apnea http://ClinicalTrials.gov/show/NCT01446601 Study 6: Isavuconazole (BAL8557) in the Treatment of Candidemia and Other Invasive Candida Infections http://ClinicalTrials.gov/show/NCT00413218

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 35 Study 7: Study 14: Comparative Trial Of Maraviroc Versus Emtricitabine/ Study Comparing BMS-790052 (Daclatasvir) to Tenofovir Both With Darunavir/Ritonavir In Telaprevir Combined With Peginterferon Alfa-2a and Antiretroviral-Naive Patients Infected With Ccr5 Tropic Ribavirin in Untreated Hepatitis C Patients HIV 1 http://ClinicalTrials.gov/show/NCT01492426 http://ClinicalTrials.gov/show/NCT01345630 Study 15: Study 8: A Study of Intravenous Tamiflu (Oseltamivir) in Ceftazidime-Avibactam Compared With Doripenem Children With Influenza Followed by Oral Therapy for Hospitalized Adults With http://ClinicalTrials.gov/show/NCT01033734 Complicated UTIs (Urinary Tract Infections) http://ClinicalTrials.gov/show/NCT01595438 Study 16: Study to Evaluate Switching From Regimens Study 9: Consisting of a Ritonavir-boosted Protease Inhibitor A Study Comparing Ceftazidime-Avibactam+ Plus Emtricitabine/Tenofovir Fixed-Dose Combination Metronidazole Versus Meropenem in Adults With to the Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Complicated Intra-abdominal Infections DF Single-Tablet Regimen in Virologically Suppressed, http://ClinicalTrials.gov/show/NCT01500239 HIV 1 Infected Patients http://ClinicalTrials.gov/show/NCT01475838 Study 10: Study 17: Isavuconazole in the Treatment of Renally Impaired Aspergillosis and Rare Fungi Safety and Efficacy of Econazole Nitrate Foam 1% and http://ClinicalTrials.gov/show/NCT00634049 Foam Vehicle in Subjects With Tinea Pedis http://ClinicalTrials.gov/show/NCT01358240 Study 11: Study 18: Phase 3b Open Label Study to Evaluate Switching From Regimens Consisting of a Non-nucleoside A Study of TMC435 in Combination With Reverse Transcriptase Inhibitor Plus Emtricitabine Peginterferon Alfa-2A and Ribavirin for Hepatitis C and Tenofovir DF to the Elvitegravir/Cobicistat/ Virus Genotype-1 Infected Patients Who Participated Emtricitabine/Tenofovir DF Single-Tablet Regimen in in a Control Group of a TMC435 Study Virologically Suppressed, HIV 1 Infected Patients http://ClinicalTrials.gov/show/NCT01323244 http://ClinicalTrials.gov/show/NCT01495702 Study 19: Study 12: Safety, Efficacy and Dose-response Study of A Phase III Study of the Safety and Efficacy of BMS-986001 in Subjects With HIV-1 Infection Who Entecavir in Pediatric Patients With Chronic Are Treatment-naive HBV-Infection http://ClinicalTrials.gov/show/NCT01489046 http://ClinicalTrials.gov/show/NCT01079806

Study 13: Safety and Efficacy Study of VP20621 for Prevention of Recurrent Clostridium Difficile Infection http://ClinicalTrials.gov/show/NCT01259726

36 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 20: Study 26: Safety and Efficacy of Darunavir/Cobicistat/ Evaluate the Safety & Bioequivalence of a Generic Emtricitabine/GS-7340 Single Tablet Regimen Versus Butenafine Cream & Lotrimin Ultra® & Compare Cobicistat-boosted Darunavir Plus Emtricitabine/ Both to a Vehicle Control in Treatment of Interdigital Tenofovir Disoproxil Fumarate Fixed Dose Tinea Pedis Combination in HIV-1 Infected, Antiretroviral http://ClinicalTrials.gov/show/NCT01580878 Treatment Naive Adults http://ClinicalTrials.gov/show/NCT01565850 Study 27: A Study to Treat Subjects With Telaprevir, Ribavirin, Study 21: and Peginterferon Who Are Coinfected With HIV and An Evaluation Of The Effectiveness And Safety Of Hepatitis C Virus (HCV) Anidulafungin Compared To Caspofungin For The http://ClinicalTrials.gov/show/NCT01467479 Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune Study 28: System Pharmacokinetics, Safety, and Tolerability of http://ClinicalTrials.gov/show/NCT00806351 Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Study 22: Invasive Fungal Infections (P05520 AM3) A Study of MK-3415, MK-6072, and MK-3415A http://ClinicalTrials.gov/show/NCT01075984 in Participants Receiving Antibiotic Therapy for Clostridium Difficile Infection (MK-3415A-001 AM2) Study 29: http://ClinicalTrials.gov/show/NCT01241552 A Clinical Trial to Study the Safety, Tolerance and Immunogenic Response to Gardasil and rLP2086 Study 23: Vaccine When Given at the Same Time to Children TMC435HPC3002 - 3-Year Follow up of Patients Between the Ages of 11 and 17 After Administration of TMC435 for the Treatment of http://ClinicalTrials.gov/show/NCT01461993 Chronic Hepatitis C. http://ClinicalTrials.gov/show/NCT01349465 Study 30: Pilot Feasibility Study With Patients Who Are at High Study 24: Risk For Developing Invasive Candidiasis in a Critical Phase 3b Open-Label, Single Arm Study to Evaluate Care Setting (MK-0991-067) the Safety and Efficacy of Cobicistat-boosted http://ClinicalTrials.gov/show/NCT01045798 Darunavir in HIV Infected Adults http://ClinicalTrials.gov/show/NCT01440569 Kidney and Liver Disorders Study 25: (17 clinical trials recruiting) Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem Study 1: in Complicated Intraabdominal Infections http://ClinicalTrials.gov/show/NCT01445678 8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) http://ClinicalTrials.gov/show/NCT01451827

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 37 Study 2: Study 10: Study of the Effect of Renal Impairment on the Study to Evaluate TRV120027 on Renal Pharmacokinetics of Isavuconazole Pharmacodynamics in Patients With Heart Failure and http://ClinicalTrials.gov/show/NCT01555866 Renal Dysfunction http://ClinicalTrials.gov/show/NCT01444872 Study 3: Study 11: A Pharmacokinetics and Safety Study in Subjects With Renal Impairment Bardoxolone Methyl Evaluation in Patients With http://ClinicalTrials.gov/show/NCT01452828 Chronic Kidney Disease and Type 2 Diabetes http://ClinicalTrials.gov/show/NCT01351675 Study 4: Study 12: A Study to Evaluate The Pharmacokinetics Of Crizotinib (PF-02341066) In Subjects With Impaired Dose-Finding Pilot Study of ACTH in Patients With Renal Function Idiopathic Membranous Nephropathy http://ClinicalTrials.gov/show/NCT01419041 http://ClinicalTrials.gov/show/NCT00805753

Study 5: Study 13: A Placebo-Controlled, Double-Blind Study to Confirm Defibrotide for Patients With Hepatic Veno-occlusive the Reversal of Hepatorenal Syndrome Type 1 With Disease (VOD): A Treatment IND Study Terlipressin http://ClinicalTrials.gov/show/NCT00628498 http://ClinicalTrials.gov/show/NCT01143246 Study 14: Study 6: Phase 3 Study of Obeticholic Acid in Patients With Pharmacokinetics of Tasimelteon in Subjects With Primary Biliary Cirrhosis Renal Impairment and Matched Control Subjects With http://ClinicalTrials.gov/show/NCT01473524 Relatively Normal Renal Function http://ClinicalTrials.gov/show/NCT01526746 Study 15: A PK and Safety Study in Subjects With Hepatic Study 7: Impairment Efficacy and Safety Study of KIACTA in Preventing http://ClinicalTrials.gov/show/NCT01431833 Renal Function Decline in AA Amyloidosis http://ClinicalTrials.gov/show/NCT01215747 Study 16: A Placebo-Controlled, Double-Blind Study to Confirm Study 8: the Reversal of Hepatorenal Syndrome Type 1 With A Dose-Escalation Study of KD019 in Subjects With Terlipressin Autosomal Dominant Polycystic Kidney Disease http://ClinicalTrials.gov/show/NCT01143246 http://ClinicalTrials.gov/show/NCT01559363 Study 17: Study 9: Double-Blind, Placebo-Controlled Study of Two Pharmacokinetic Assessment of Single-Dose Doses of EPA-E in Patients With Non Alcoholic Odanacatib (MK-0822) in Subjects With Severe Renal Steatohepatitis (NASH) Insufficiency (MK-0822-067 AM1) http://ClinicalTrials.gov/show/NCT01154985 http://ClinicalTrials.gov/show/NCT01512667

38 PhRMA • Pharmaceutical Clinical Trials in Minnesota Mental Illnesses Study 7: (10 clinical trials recruiting) A Study Of DVS SR In Treatment Of Children And Adolescent Outpatients With MDD Study 1: http://ClinicalTrials.gov/show/NCT01372150 A Study of RO4917838 in Patients With Persistent, Study 8: Predominant Negative Symptoms of Schizophrenia (WN25309) A Study of RO4917838 in Patients With Sub-optimally Controlled Symptoms of Schizophrenia (WN25306) http://ClinicalTrials.gov/show/NCT01192906 http://ClinicalTrials.gov/show/NCT01235585 Study 2: Study 9: A 6-Month Open-Label Extension Study to the B2061014 Study to Evaluate the Safety, Tolerability and A Randomized, Clinical Trial of Vitamin E and Efficacy of DVS SR in the Treatment of Children and Memantine in Alzheimer’s Disease Adolescents With MDD http://ClinicalTrials.gov/show/NCT00235716 http://ClinicalTrials.gov/show/NCT01371721 Study 10: Study 3: Seroquel 2Extended Release (XR) for the Management Safety and Tolerability of Aripiprazole in Adolescents of Borderline Personality Disorder (BPD) With Schizophrenia or Children and Adolescents With http://ClinicalTrials.gov/show/NCT00880919 Bipolar I Disorder, Manic or Mixed Episode With or Without Psychotic Features http://ClinicalTrials.gov/show/NCT01122927 Respiratory Diseases (19 clinical trials recruiting) Study 4: Study to Evaluate the Efficacy and Safety of Study 1: Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Efficacy, Safety and Tolerability of Aclidinium Disorder Bromide/Formoterol Fumarate Compared With Formoterol Fumarate in Patients With Moderate http://ClinicalTrials.gov/show/NCT01072630 to Severe Chronic Obstructive Pulmonary Disease (COPD) Study 5: http://ClinicalTrials.gov/show/NCT01437397 Open-label Study to Compare Hospitalization Rates of Schizophrenic Patients Treated With Oral Study 2: Antipsychotics Versus IM Depot Aripiprazole Efficacy, Safety, and Tolerability of SAR231893 http://ClinicalTrials.gov/show/NCT01432444 (REGN668) in Patients With Persistent Moderate to Severe Eosinophilic Asthma Study 6: http://ClinicalTrials.gov/show/NCT01312961 Efficacy and Safety Study of Low-Dose Ondansetron For Adjunctive Therapy In Adult Patients With Study 3: Obsessive-Compulsive Disorder Safety Study in Adolescent and Adult Patients With http://ClinicalTrials.gov/show/NCT01275248 Asthma http://ClinicalTrials.gov/show/NCT01476904

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 39 Study 4: Study 11: A Study to Characterize the Safety, PK and Biological A Study of the Effectiveness and Safety of Different Activity of CC-930 in Idiopathic Pulmonary Fibrosis Doses of Fluticasone Propionate Taken From a Dry (IPF) Powder Inhaler (Puffer) in Adolescents and Adults Who http://ClinicalTrials.gov/show/NCT01203943 Have Asthma That is Not Controlled by High Dose Inhaled Corticosteroid Asthma Medications Study 5: http://ClinicalTrials.gov/show/NCT01576718 A Study of Lebrikizumab in Patients With Uncontrolled Study 12: Asthma Who Are on Inhaled Corticosteroids and A Second Controller Medication (VERSE) Study To Evaluate The Efficacy And Safety Of http://ClinicalTrials.gov/show/NCT01545453 PH-797804 For 12 Weeks In Adults With Moderate To Severe Chronic Obstructive Pulmonary Disease Study 6: (COPD) On A Background Of Tiotropium Bromide http://ClinicalTrials.gov/show/NCT01543919 Tiotropium +Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Study 13: Obstructive Pulmonary Disease (COPD) http://ClinicalTrials.gov/show/NCT01431287 A Study to See if AZLI (an Inhaled Antibiotic) is Effective in Treating Adults With Non-CF Study 7: Bronchiectasis—AIR-BX1 http://ClinicalTrials.gov/show/NCT01313624 A Study of ARRY-502 in Patients With Persistent Asthma Study 14: http://ClinicalTrials.gov/show/NCT01561690 Dose Finding Study for QAW039 in Asthma Study 8: http://ClinicalTrials.gov/show/NCT01437735 Safety of QMF149 Twisthaler® in Adolescent and Adult Study 15: Patients With Asthma http://ClinicalTrials.gov/show/NCT00941798 Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients Study 9: http://ClinicalTrials.gov/show/NCT01533935 A Study of the Effectiveness and Safety of Different Study 16: Doses of Fluticasone Propionate Taken From a Dry Powder Inhaler in Adolescents and Adults Who Have A Study to Evaluate the Efficacy and Safety of Asthma That is Not Controlled by Asthma Medications Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Not Containing Steroids Patients (12-75 Years of Age) With Eosinophilic http://ClinicalTrials.gov/show/NCT01479621 Asthma http://ClinicalTrials.gov/show/NCT01270464 Study 10: Study 17: Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Safety and Efficacy of BIBF 1120 at High Dose in Moderate Persistent Asthma Idiopathic Pulmonary Fibrosis Patients http://ClinicalTrials.gov/show/NCT01257230 http://ClinicalTrials.gov/show/NCT01335464

40 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 18: Study 2: Safety and Efficacy of BIBF 1120 at High Dose in Study Assessing Double-masKed Uveitis tReAtment Idiopathic Pulmonary Fibrosis Patients II http://ClinicalTrials.gov/show/NCT01358266 http://ClinicalTrials.gov/show/NCT01335477 Study 3: Study 19: Multicenter Study Using Glaukos® Trabecular Glycopyrrolate/Formoterol Fumarate MDI Compared Micro-Bypass Stent Model GTS400 Using the G2-M-IS With Spiriva® as An Active Control in Patients With Injector System in Conjunction With Cataract Surgery Moderate to Severe Chronic Obstructive Pulmonary http://ClinicalTrials.gov/show/NCT01461291 Disease http://ClinicalTrials.gov/show/NCT01587079 Study 4: Safety Study of the VEGA UV-A System to Treat Ectasia OTHER DISEASES http://ClinicalTrials.gov/show/NCT01398839

Allergies Study 5: (3 clincial trials recruiting) Safety and Effectiveness Study of the VEGA UV-A System for Cross-linking in Eyes With Keratoconus and Study 1: Ectasia http://ClinicalTrials.gov/show/NCT01398852 Efficacy and Safety of 4 Doses of QGE031 in Patients 18-50 Years of Age With Peanut Allergy http://ClinicalTrials.gov/show/NCT01451450 Hemophilia/Blood Disorders Study 2: (7 clinical trials recruiting) A Safety and Efficacy Study of Ciclesonide Nasal Aerosol in Subjects 6-11 Years With Perennial Allergic Study 1: Rhinitis (PAR). An Open-label, Randomized, Multicenter Phase IIIb http://ClinicalTrials.gov/show/NCT01451541 Study to Assess the Efficacy, Safety and Tolerance of BERIPLEX® P/N Compared With Plasma for Rapid Study 3: Reversal of Coagulopathy Induced by Vitamin K Antagonists in Subjects Requiring an Urgent Surgical A Safety and Efficacy Study of Ciclesonide Nasal Procedure Aerosol in Subjects 6-11 Years With Seasonal Allergic Rhinitis (SAR) http://ClinicalTrials.gov/show/NCT00803101 http://ClinicalTrials.gov/show/NCT01458275 Study 2: A Trial Investigating Safety and Efficacy of Treatment Eye Disorders With BAY94-9027 in Severe Hemophilia A (5 clinical trials recruiting) http://ClinicalTrials.gov/show/NCT01580293 Study 3: Study 1: Safety and Efficacy of NNC-0156-0000-0009 After A Clinical Trial to Evaluate a Corneal Inlay for the Long-Term Exposure in Patients With Haemophilia B: Improvement of Near Vision in Presbyopic Patients An Extension to Trials NN7999-3747 and NN7999-3773 http://ClinicalTrials.gov/show/NCT01373580 http://ClinicalTrials.gov/show/NCT01395810

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 41 Study 4: Psoriasis/Skin Disorders Compassionate Use of Mepolizumab in Subjects With (9 clinical trials recruiting) Hypereosinophilic Syndrome (HES) http://ClinicalTrials.gov/show/NCT00244686 Study 1: Study 5: Efficacy and Safety Study of Adalimumab in Treatment of Hidradenitis Suppurativa Safety and Efficacy of Polymyxin B Hemoperfusion http://ClinicalTrials.gov/show/NCT01468207 (PMX) for Septic Shock http://ClinicalTrials.gov/show/NCT01046669 Study 2: Study 6: Efficacy and Safety of Subcutaneous Secukinumab (AIN457) for Moderate to Severe Chronic Plaque-type Evaluation of Safety and Efficacy, Including Psoriasis Assessing Different Doses and Dose Regimens Pharmacokinetics, of NNC 0129-0000-1003 When http://ClinicalTrials.gov/show/NCT01406938 Administered for Treatment and Prophylaxis of Bleeding in Subjects With Haemophilia A Study 3: http://ClinicalTrials.gov/show/NCT01480180 A Study of Ustekinumab to Evaluate a Study 7: “Subject-tailored” Maintenance Dosing Approach in Subjects With Moderate-to-Severe Plaque Psoriasis Study of Efficacy and Safety in Polycythemia Vera http://ClinicalTrials.gov/show/NCT01550744 Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Study 4: Tablets Versus Best Available Care: (The RESPONSE Trial) A Long Term Study To Evaluate The Safety And http://ClinicalTrials.gov/show/NCT01243944 Tolerability Of CP-690,550 For Patients With Moderate To Severe Chronic Plaque Psoriasis http://ClinicalTrials.gov/show/NCT01163253 Lupus Study 5: (3 clinical trials recruiting) A Sequential Treatment Regimen of Cryotherapy and Picato® for the Treatment of Actinic Keratosis on the Study 1: Face and Scalp A Research Study to Assess if CC-930 is Safe in http://ClinicalTrials.gov/show/NCT01541553 Treating Subjects With Discoid Lupus Erythematosus http://ClinicalTrials.gov/show/NCT01466725 Study 6: Evaluation of the Efficacy, Safety and Toleration of Study 2: CT327 Ointment in Patients With Psoriasis Vulgaris A Study of LY2127399 in Patients With Systemic Lupus http://ClinicalTrials.gov/show/NCT01465282 Erythematosus http://ClinicalTrials.gov/show/NCT01205438 Study 7: Phase 2 Study of HL-009 Liposomal Gel to Treat Mild Study 3: to Moderate Atopic Dermatitis A Study of LY2127399 in Patients With Systemic Lupus http://ClinicalTrials.gov/show/NCT01568489 Erythematosus http://ClinicalTrials.gov/show/NCT01196091

42 PhRMA • Pharmaceutical Clinical Trials in Minnesota Study 8: Study 6: A Study of DER 45-EV Gel to Treat Rosacea Calcineurin Inhibitor Sparing After Kidney http://ClinicalTrials.gov/show/NCT00940992 Transplantation http://ClinicalTrials.gov/show/NCT01062555 Study 9: Study 7: Short-incubation Levulan Photodynamic Therapy Versus Vehicle for Face/Scalp Actinic Keratosis (AK) Dosing Regimen of Eculizumab Added to http://ClinicalTrials.gov/show/NCT01475955 Conventional Treatment in Positive Crossmatch Deceased Donor Kidney Transplant http://ClinicalTrials.gov/show/NCT01106027 Transplantation Study 8: (8 clinical trials recruiting) Eculizumab Added to Conventional Treatment in the Prevention of Antibody-mediated Rejection in ABO Study 1: Blood Group Incompatible Living Donor Kidney Efficacy, Safety, Tolerability, Pharmacokinetics of Transplantation Sotrastaurin-tacrolimus vs. Mycophenolic http://ClinicalTrials.gov/show/NCT01095887 Acid-tacrolimus in de Novo Liver Transplant Patients http://ClinicalTrials.gov/show/NCT01128335 Other Diseases Study 2: (18 clinical trials recruiting) I5NP for Prophylaxis of Delayed Graft Function in Kidney Transplantation Study 1: http://ClinicalTrials.gov/show/NCT00802347 Effects of Tolvaptan vs Fluid Restriction in Study 3: Hospitalized Subjects With Dilutional Hyponatremia http://ClinicalTrials.gov/show/NCT01227512 CIS001 Extension Study of Cyclosporine Inhalation Solution Study 2: http://ClinicalTrials.gov/show/NCT00938236 Safety and Efficacy of OMS103HP-S Administered Study 4: in Joint Irrigation Solution to Subjects Undergoing Arthroscopic Meniscectomy Safety & Efficacy of Eculizumab to Prevent AMR in http://ClinicalTrials.gov/show/NCT01406561 Living Donor Kidney Transplant Recipients Requiring Desensitization Study 3: http://ClinicalTrials.gov/show/NCT01399593 Prospective Aneurysm Trial: High Angle Aorfix™ Study 5: Bifurcated Stent Graft http://ClinicalTrials.gov/show/NCT00522535 Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients Study 4: http://ClinicalTrials.gov/show/NCT01150097 Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD http://ClinicalTrials.gov/show/NCT01485796

Developing Cures, Creating Jobs • A Partnership Between Biopharmaceutical Companies And State Research Institutions 43 Study 5: Study 12: Safety and Efficacy Pre-Menopausal Women With Clinical Study to Determine if Ecopipam Can Reduce Heavy Uterine Bleeding and Uterine Fibroids Urges to Gamble http://ClinicalTrials.gov/show/NCT01441635 http://ClinicalTrials.gov/show/NCT01215357

Study 6: Study 13: Study of Oral MLN9708 in Adult Patients With A Study of the Efficacy and Safety of MK-4618 in Relapsed or Refractory Light Chain Amyloidosis Patients With Overactive Bladder (OAB) (MK-4618-008 http://ClinicalTrials.gov/show/NCT01318902 AM3 EXT1[AM2]) http://ClinicalTrials.gov/show/NCT01314872 Study 7: Study 14: The Kiva® System as a Vertebral Augmentation Treatment Clinical Evaluation of NX-1207 for the Treatment of http://ClinicalTrials.gov/show/NCT01123512 Benign Prostatic Hyperplasia (BPH) NX02-0018 http://ClinicalTrials.gov/show/NCT00945490 Study 8: Study 15: An Extension Study to Evaluate the Long-Term Safety of FCFD4514S in Patients With Geographic Atrophy Effects of Exenatide on Hypothalamic Obesity http://ClinicalTrials.gov/show/NCT01602120 http://ClinicalTrials.gov/show/NCT01061775

Study 9: Study 16: Clinical Study to Investigate the Effectiveness of the The Testosterone Trial in Older Men TOPAS Sling System to Treat Fecal Incontinence http://ClinicalTrials.gov/show/NCT00799617 http://ClinicalTrials.gov/show/NCT01090739 Study 17: Study 10: Rituxima3b in IgG4-related Disease: A Phase 1-2 Trial Safety and Effectiveness Trial of the Ventana http://ClinicalTrials.gov/show/NCT01584388 Fenestrated Stent Graft System http://ClinicalTrials.gov/show/NCT01491945 Study 18: Implantable Systems Performance Registry (ISPR) Study 11: http://ClinicalTrials.gov/show/NCT00959296 Human Heterologous Liver Cells for Infusion in Children With Urea Cycle Disorders http://ClinicalTrials.gov/show/NCT01195753

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