DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,708.371 B2 Kessler Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,708.371 B2 Kessler Et Al USOO9708371B2 (12) United States Patent (10) Patent No.: US 9,708.371 B2 Kessler et al. (45) Date of Patent: Jul.18, 2017 (54) TREATMENTS FOR GASTROINTESTINAL 5,654,278 A 8/1997 Sorensen DSORDERS 5,904,935 A 5/1999 Eckenhoff et al. 6,068,850 A 5, 2000 Stevenson et al. 6,124,261 A 9, 2000 Stevenson et al. (75) Inventors: Marco Kessler, Danvers, MA (US); 6,541,606 B2 4/2003 Margolin et al. Angelika Fretzen, Somerville, MA 6,734,162 B2 5/2004 Van Antwerp (US); Hong Zhao, Lexington, MA 6,828.303 B2 12/2004 Kim et al. (US); Robert Solinga, Brookline, MA 36.3% E: 1339. SN. (US); Vladimir Volchenok, Waltham, 7,056,942- - - B2 6/2006 HildesheimOK et al. MA (US) 7,141,254 B2 11/2006 Bhaskaran et al. 7,304,036 B2 * 12/2007 Currie .................. CO7K 14,245 (73) Assignee: Ironwood Pharmaceuticals, Inc., 514,122 Cambridge, MA (US) 7.351,798 B2 4/2008 Margolin et al. 7,371,727 B2 5/2008 Currie et al. (*)c Notice:- r Subject to any disclaimer, the term of this 7,704,9477,494,979 B2 4/20102/2009 Currie et al. patent is extended or adjusted under 35 7,745,409 B2 6/2010 Currie et al. U.S.C. 154(b) by 364 days. (Continued) (21) Appl. No.: 14/239,178 FOREIGN PATENT DOCUMENTS (22) PCT Filed: Aug. 17, 2012 JP 64-009938 1, 1989 JP 2003-2012.56 T 2003 (86). PCT No.: PCT/US2012/051289 (Continued) S 371 (c)(1), (2), (4) Date: Nov. 21, 2014 OTHER PUBLICATIONS (87) PCT Pub. No.: WO2013/025969 Maier et al. Analogues of Human Calcitonin II. Influence of Modifications in Amino Acid Positions 1, 8 and 22 on PCT Pub. Date: Feb. 21, 2013 Hypocalcemic Activity in the Rat. Hormon. Me tab. Res. 7 (1975) 511-5.14. (65) Prior Publication Data Armed, Hashim and Shah, Navnit., "Formulations of Low Dose Medicines—Theory and Practice.” American Pharmaceutical US 2015/OO9.4272 A1 Apr. 2. 2015 Review, 3(3): 1-4, 2000. Andresen et al., “Effect of 5 days of linaclotide on transit and bowel O O function in females with constipation-predominant irritable bowel Related U.S. Application Data syndrome.” Gastroenterology, 133(3):761-768, 2007. (60) Provisional application No. 61/524.699, filed on Aug. Assis, Linaclotide Acetate.” Drugs of the Future, 33(7): 17, 2011. Angelastro et al., “An efficient synthesis of novel alpha-diketone and alpha-keto ester derivatives of N-protected amino acids and (51) Int. Cl. peptides.” The Journal of Organic Chemistry, 54(16):3913-6, 1989. C07K 7/08 (2006.01) Aventis Pharmaceuticals, Inc. (2002). DDAVP (desmopressin CLID 3/34 (2006.01) acetate) tablet, Product Label). Bridgewater, NJ 08807, USA. C07K 7/54 (2006.01) (Continued) C07K 5/02 (2006.01) Primary Examiner — Satyanarayana R. Gudibande A6 IK 38/10 (2006.01) Assistant Examiner — Jia-Hai Lee A6 IK 38/12 (2006.01) (74) Attorney, Agent, or Firm — Honigman Miller A6 IK 45/06 (2006.01) Schwartz and Cohn LLP. Kelly T. Murphy; Jonathan P. (52) U.S. Cl. O’Brien CPC (2013.01);................ A61KC07K 38/12 7/08 (2013.01); A61K 38/1045/06 (57) ABSTRACT (2013.01); C07K 5/02 (2013.01); C07K 7/54 The present invention features peptides, compositions, and (2013.01): CIID 3/3436 (2013.01); G0IN related methods for treating gastrointestinal disorders and 2800/065 (2013.01) conditions, including but not limited to, irritable bowel (58) Field of Classification Search syndrome (IBS), gastrointestinal motility disorders, func None tional gastrointestinal disorders, gastroesophageal reflux See application file for complete search history. disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional (56) References Cited heartburn, dyspepsia, Visceral pain, gastroparesis, chronic U.S. PATENT DOCUMENTS intestinal pseudo-obstruction (or colonic pseudo-obstruc tion), disorders and conditions associated with constipation, 4,544,568 A 10/1985 Heyland et al. 4,806.524. A 2/1989 Kawaguchi and other conditions and disorders are described herein, 4,992,419 A 2/1991 Woog et al. using peptides and other agents that activate the guanylate 5,221,495 A 6, 1993 Cao cyclase C (GC-C) receptor. 5,451.410 A 9, 1995 Milstein 5,593,696 A 1/1997 McNally et al. 28 Claims, 3 Drawing Sheets US 9,708.371 B2 Page 2 (56) References Cited OTHER PUBLICATIONS U.S. PATENT DOCUMENTS Bedul-Addo, F. et al., “Preformulation Development of Recombi nant Pegylated Staphylokinase SY161 Using Statistical Design.” 7,767,644 B2 8, 2010 Schumann et al. 7,772,188 B2 8, 2010 Currie et al. AAPS PharmSci (http://www.aapspharmsci.org), 4(4) article 19, 7.910,546 B2 3, 2011 Currie et al. 1-11, 2002. 8,080,526 B2 * 12/2011 Currie ...................... CO7K7/08 Bedul-Addo, F.K. et al., “Use of Biophysical Characterization in 514,215 Preformulation Development of a Heavy-Chain Fragment of Botu 8, 101,579 B2 1, 2012 Currie et al. linum Serotype B: Evalulation of Suitable Purification Process 8, 110,553 B2 2, 2012 Currie et al. Conditions.” Pharmaceutical Research, 21 (8): 1353-1361, 2004. 8,748,573 B2 * 6/2014 Fretzen ................... 530/327 Busby et al., "Linaclotide, through activation of guanylate cyclase 8,802,628 B2* 8/2014 Fretzen ................ A61K9/1611 514, 20.6 C, acts locally in the gastrointestinal tract to elictly enhanced 8,933,030 B2 1/2015 Fretzen et al. intestinal secretion and transit.” Eur, J. Pharmacol. 649(1-3): 328 2003,0003563 A1 1, 2003 Vinkemeier et al. 335, 2010. 2003, OO691.82 A1 4, 2003 Rinella Camilleri et al., “Challenges to the Therapeutic Pipeline for Irritable 2003, OO73628 A1 4, 2003 Shailubhai et al. Bowel Syndrome: End Points and Regulatory Hurdles.” Gastroen 2003. O104996 A1 6, 2003 Li et al. terology. 135:1877-1891, 2008. 2003/0175230 A1 9, 2003 Dubief Camilleri, “Management of the Irritable Bowel Syndrome” Gastro 2004/0265242 A1 12, 2004 Bartus enterology, 120:652-668, 2001. 2004/0266989 A1 12, 2004 Currie Capasso et al., “Deamidation via Cyclic Imide of Asparaginyl 2005.0020811 A1 1/2005 Currie et al. Peptides: Dependence on Salts, Buffers and Organic Solvents.” 2005, 0080009 A1 4, 2005 Metzner et al. Peptide Research, 4(4): 234-238, 1991. 2006/0258593 A1 11, 2006 Currie et al. Carpenter et al., “Rational Design of Stable Lyophilized Protein 2007/O122354 A1 5/2007 Hastedt et al. Formulations: Some Practical Advice.' Pharmaceutical Research, 2007. O1544.06 A1 7/2007 Moon et al. 14(8): 969-975, 1997. 2007/0202165 A1 8, 2007 Heuer et al. Carson et al., “Effect of Linaclotide on Quality of Life in Adults 2007/0225216 A1* 9, 2007 MerZouk ................ A61K 38/12 With Chronic Constipation: Results From 2 Randomized, Double 514f13.3 Blind, Placebo-Controlled Phase III Trials.” Gastroenterology, 2009/O110729 A1 4, 2009 Giovannone et al. 139(1):E19, 2010. 2009,0253634 A1 10, 2009 Currie et al. Chourasia, M.K. and Jain, S.K., “Pharmaceutical approaches to 2009/0305993 A1 12, 2009 Currie colon targeted drug delivery systems.” J Pharm Pharmaceut Sci 2010.0048489 A1 2, 2010 Fretzen et al. (www.ualberta.ca/-csps), 6(1): 33-66, 2003. 2010O221329 A1 9, 2010 Shailubhai et al. Cleland et al., “The Development of Stable Protein Formulations: A 2012,0009225 A1 1, 2012 Fretzen et al. Close Look at Protein Aggregation, Deamidation, and Oxidation.” 2012/0039949 A1 2, 2012 Fretzen et al. Critical Reviews in Therapeutic Drug Carrier Systems, 10(4): 2012fO213846 A1 8, 2012 Fretzen et al. 307-377, 1993. 2013, OO12454 A1 1, 2013 Mo et al. Constantino, H.R. et al., “Moisture-Induced Aggregation of 2013, O190239 A1 T/2013 Fretzen et al. Lyophilized Insulin’. Pharmaceutical Research, 11(1): 21-29, 1994. 2013/0273.169 A1 10, 2013 Fretzen et al. Cook et al., “Chronic constipation: Overview and Challenges.” Neurogastroenterology and Motility, 21(supp2): 1-8, 2009. FOREIGN PATENT DOCUMENTS Dulbecco et al., “Plaque formation and isolation of pure liner with poliomyelitis viruses.” Journal of Experimental Medicine, 99(2): WO WO9012029 10, 1990 WO WO9104743 4f1991 167-182, 1954. WO WO9703692 2, 1997 Elan Pharmaceuticals, Inc. (2004). PRIALT (Ziconotide) injection, WO WO9704796 2, 1997 solution, Product Label. San Diego, CA 92121, USA. WO WO98OO152 1, 1998 Fix, J.A., “Oral Controlled Release Technology for Peptides: Status WO WO98OO157 1, 1998 and Future Prospects.” Pharmaceutical Research, 13(12): 1760 WO WOOOO488O 2, 2000 1764, 1996. WO WOOO32172 6, 2000 Forest, “Phase III randomized double-blind placebo-controlled trial WO WOO226248 4/2002 of linaclotide administered to patients with chronic constipation.” WO WOO2O78683 10, 2002 2008. Retrieved from <<http:www.clinicaltrials.gov) identifier WO WOO3.014304 2, 2003 NCT00765882 on Dec. 9, 2010. WO WOO3055511 T 2003 Fu et al., “Protein Stability in Controlled-Release Systems.” Nature WO WOO2O62369 8, 2003 Biotechnology, 18: 24-25, 2000. WO WO2004.052343 6, 2004 WO WO2004O69165 8, 2004 Grenha et al., "Chitosan nanoparticles are compatible with respi WO WO2004 108152 12, 2004 ratory epithelial cells in vitro.” European Journal of Pharmaceutical WO WO2005O14025 2, 2005 Sciences, 31: 73-84, 2007. WO WO2005042O29 5, 2005 Harris et al., “Drug evaluation: Linaclotide, a new direction in the WO WO2005087797 9, 2005 treatment of irritable bowel syndrome and chronic constipation.” WO WO2007022531 2, 2007 Current Opinion in Molecular Therapeutics, 9(4):403-410, 2007. WO WO2007044375 4/2007 Harris, “Constipation: Linaclotide—a stimulating new drug for WO WO2O08006125 1, 2008 chronic constipation.” Nature Reviews Gastroenterology and WO WO2O0802.1133 2, 2008 Hepatology, 7(7):365-6, 2010. WO WO2O08027854 3, 2008 “International Nonproprietary Names for Pharmaceutical Sub WO WO2O08078189 T 2008 stances (INN).” WHO Drug Information, 21(3): 247-264, 2007.
Load more

Recommended publications
  • Endogenous Opioid Analgesia in Peripheral Tissues and the Clinical Implications for Pain Control
    REVIEW Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control Daniel Kapitzke1,2 Abstract: Opioid receptors are widely expressed in the central and peripheral nervous system Irina Vetter1,2 as well as in numerous nonneuronal tissues. Both animal models and human clinical data Peter J Cabot2 support the involvement of peripheral opioid receptors in analgesia, particularly in inflammation where both opioid receptor expression and efficacy are increased. Immune cells have been 1 These authors contributed equally β to this work. 2School of Pharmacy, shown to contain numerous opioid peptides such as -endorphin (END), met-enkephalin University of Queensland, 4072, (ENK), and dynorphin-A (DYN), although the predominant opioid peptide involved in immune- Australia cell mediated antinociception is thought to be END. These opioid-containing immune cells migrate to inflamed tissues during a complex process of recruitment by chemokines, adhesion, and extravasation. In these tissues, opioid peptide is released from the immune cells upon stimulation with corticotrophin-releasing factor (CRF), noradrenaline, and interleukin 1β (IL-1β), and the immune cells return to the local lymph node depleted of peptide. Consistent with this model, systemic immunosuppression may lead to impaired endogenous analgesia as competent immune cells are essential to achieve release of endogenous opioid peptides within inflamed tissue. A further level of complexity is added by the observation that exogenous opioids may impair immune cell function, although there is some evidence to suggest that endogenous opioid peptides do not share this immunosuppressive effect. Improving our understanding of endogenous opioid mechanisms will provide valuable insight towards the development of novel treatments for pain with improved side effect profiles.
    [Show full text]
  • Peptide Therapeutics Designing a Science-Led Strategic Quality Control Program
    BioProcess International Peptide SPECIAL REPORT Therapeutics Designing a Science-Led Strategic Quality Control Program INTERTEK PHARMACEUTICAL SERVICES Your partner for regulatory-driven, phase appropriate analytical programs tailored to your molecule. Our experts help you to navigate the challenges of development, regulatory submission, and manufacturing. Peptide Therapeutics Designing a Science-Led Strategic Quality Control Program Shashank Sharma and Hannah Lee ince the emergence of peptide therapeutics in the 1920s with the advent of insulin therapy, the market for this product class has continued to expand with global revenues anticipatedS to surpass US$50 billion by 2024 (1). The growth of peptide therapeutics is attributed not only to improvements in manufacturing, but also to a rise in demand because of an increasingly aging population that is driving an increase in the occurrence of long-term diseases. The need for efficient and low-cost drugs and rising investments in research and development of novel drugs continues to boost market growth and fuel the emergence of generic versions that offer patients access to vital medicines at low costs. North America has been the dominant market for peptide therapeutics, with the Asia–Pacific region Insulin molecular model; the first therapeutic expected to grow at a faster rate. The global peptides use of this peptide hormone was in the market has attracted the attention of key players 1920s to treat diabetic patients. within the pharmaceutical industry, including Teva Pharmaceuticals, Eli Lilly, Novo Nordisk, Pfizer, amino acids to be peptides. Within that set, those Takeda, and Amgen. Those companies have made containing 10 or more are classed as polypeptides.
    [Show full text]
  • Linaclotide: a Novel Therapy for Chronic Constipation and Constipation- Predominant Irritable Bowel Syndrome Brian E
    Linaclotide: A Novel Therapy for Chronic Constipation and Constipation- Predominant Irritable Bowel Syndrome Brian E. Lacy, PhD, MD, John M. Levenick, MD, and Michael D. Crowell, PhD, FACG Dr. Lacy is Section Chief of Gastroenter- Abstract: Chronic constipation and irritable bowel syndrome ology and Hepatology and Dr. Levenick (IBS) are functional gastrointestinal disorders that significantly is a Gastroenterology Fellow in the affect patients’ quality of life. Chronic constipation and IBS are Division of Gastroenterology and prevalent—12% of the US population meet the diagnostic crite- Hepatology at Dartmouth-Hitchcock Medical Center in Lebanon, New ria for IBS, and 15% meet the criteria for chronic constipation— Hampshire. Dr. Crowell is a Professor and these conditions negatively impact the healthcare system of Medicine in the Division of from an economic perspective. Despite attempts at dietary Gastroenterology and Hepatology at modification, exercise, or use of over-the-counter medications, Mayo Clinic in Scottsdale, Arizona. many patients have persistent symptoms. Alternative treatment options are limited. This article describes linaclotide (Linzess, Address correspondence to: Dr. Brian E. Lacy Ironwood Pharmaceuticals/Forest Pharmaceuticals), a new, first- Division of Gastroenterology and in-class medication for the treatment of chronic constipation Hepatology, Area 4C and constipation-predominant IBS. Dartmouth-Hitchcock Medical Center 1 Medical Center Drive Lebanon, NH 03756; Tel: 603-650-5215; Fax: 603-650-5225; onstipation is
    [Show full text]
  • Laxatives for the Management of Constipation in People Receiving Palliative Care (Review)
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Laxatives for the management of constipation in people receiving palliative care (Review) Candy B, Jones L, Larkin PJ, Vickerstaff V, Tookman A, Stone P This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 5 http://www.thecochranelibrary.com Laxatives for the management of constipation in people receiving palliative care (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 4 METHODS ...................................... 4 RESULTS....................................... 7 Figure1. ..................................... 8 Figure2. ..................................... 9 Figure3. ..................................... 10 DISCUSSION ..................................... 13 AUTHORS’CONCLUSIONS . 14 ACKNOWLEDGEMENTS . 14 REFERENCES ..................................... 15 CHARACTERISTICSOFSTUDIES . 17 DATAANDANALYSES. 26 ADDITIONALTABLES. 26 APPENDICES ..................................... 28 WHAT’SNEW..................................... 35 HISTORY....................................... 35 CONTRIBUTIONSOFAUTHORS . 36 DECLARATIONSOFINTEREST . 36 SOURCESOFSUPPORT . 36 DIFFERENCES
    [Show full text]
  • Chronic Constipation: an Evidence-Based Review
    J Am Board Fam Med: first published as 10.3122/jabfm.2011.04.100272 on 7 July 2011. Downloaded from CLINICAL REVIEW Chronic Constipation: An Evidence-Based Review Lawrence Leung, MBBChir, FRACGP, FRCGP, Taylor Riutta, MD, Jyoti Kotecha, MPA, MRSC, and Walter Rosser MD, MRCGP, FCFP Background: Chronic constipation is a common condition seen in family practice among the elderly and women. There is no consensus regarding its exact definition, and it may be interpreted differently by physicians and patients. Physicians prescribe various treatments, and patients often adopt different over-the-counter remedies. Chronic constipation is either caused by slow colonic transit or pelvic floor dysfunction, and treatment differs accordingly. Methods: To update our knowledge of chronic constipation and its etiology and best-evidence treat- ment, information was synthesized from articles published in PubMed, EMBASE, and Cochrane Database of Systematic Reviews. Levels of evidence and recommendations were made according to the Strength of Recommendation taxonomy. Results: The standard advice of increasing dietary fibers, fluids, and exercise for relieving chronic constipation will only benefit patients with true deficiency. Biofeedback works best for constipation caused by pelvic floor dysfunction. Pharmacological agents increase bulk or water content in the bowel lumen or aim to stimulate bowel movements. Novel classes of compounds have emerged for treating chronic constipation, with promising clinical trial data. Finally, the link between senna abuse and colon cancer remains unsupported. Conclusions: Chronic constipation should be managed according to its etiology and guided by the best evidence-based treatment.(J Am Board Fam Med 2011;24:436–451.) copyright. Keywords: Chronic Constipation, Clinical Review, Evidence-Based Medicine, Family Medicine, Gastrointestinal Problems, Systematic Review The word “constipation” has varied meanings for was established in 1991 by Drossman et al, primar- different individuals.
    [Show full text]
  • Relative Efficacy of Tegaserod in a Systematic Review and Network Meta-Analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation
    This is a repository copy of Relative Efficacy of Tegaserod in a Systematic Review and Network Meta-analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation.. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/149160/ Version: Accepted Version Article: Black, CJ, Burr, NE orcid.org/0000-0003-1988-2982 and Ford, AC orcid.org/0000-0001-6371-4359 (2020) Relative Efficacy of Tegaserod in a Systematic Review and Network Meta-analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation. Clinical Gastroenterology and Hepatology, 18 (5). 1238-1239.E1. ISSN 1542-3565 https://doi.org/10.1016/j.cgh.2019.07.007 © 2019 by the AGA Institute. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/). Reuse This article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can’t change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Black et al. Page 1 of 9 Accepted for publication 3rd July 2019 TITLE PAGE Title: Relative Efficacy of Tegaserod in a Systematic Review and Network Meta- analysis of Licensed Therapies for Irritable Bowel Syndrome with Constipation.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]
  • WHO Drug Information Vol
    WHO Drug Information Vol. 26, No. 4, 2012 WHO Drug Information Contents International Regulatory Regulatory Action and News Harmonization New task force for antibacterial International Conference of Drug drug development 383 Regulatory Authorities 339 NIBSC: new MHRA centre 383 Quality of medicines in a globalized New Pakistan drug regulatory world: focus on active pharma- authority 384 ceutical ingredients. Pre-ICDRA EU clinical trial regulation: public meeting 352 consultation 384 Pegloticase approved for chronic tophaceous gout 385 WHO Programme on Tofacitinib: approved for rheumatoid International Drug Monitoring arthritis 385 Global challenges in medicines Rivaroxaban: extended indication safety 362 approved for blood clotting 385 Omacetaxine mepesuccinate: Safety and Efficacy Issues approved for chronic myelo- Dalfampridine: risk of seizure 371 genous leukaemia 386 Sildenafil: not for pulmonary hyper- Perampanel: approved for partial tension in children 371 onset seizures 386 Interaction: proton pump inhibitors Regorafenib: approved for colorectal and methotrexate 371 cancer 386 Fingolimod: cardiovascular Teriflunomide: approved for multiple monitoring 372 sclerosis 387 Pramipexole: risk of heart failure 372 Ocriplasmin: approved for vitreo- Lyme disease test kits: limitations 373 macular adhesion 387 Anti-androgens: hepatotoxicity 374 Florbetapir 18F: approved for Agomelatine: hepatotoxicity and neuritic plaque density imaging 387 liver failure 375 Insulin degludec: approved for Hypotonic saline in children: fatal diabetes mellitus
    [Show full text]
  • Systematic Literature Review and Indirect Treatment Comparison Of
    PGI8 Systematic literature review and indirect treatment comparison of linaclotide versus other oral constipation treatments in patients with chronic constipation H Okumura,1 W Tang,2 K Iwasaki,2 S Shoji,1 T Odaka,3 A Nakajima4 1Astellas Pharma Inc., Tokyo, Japan; 2Milliman Inc., Tokyo, Japan; 3Odaka Medical and Gastrointestinal Clinic, Chiba, Japan; 4Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan INTRODUCTION Figure 2. Treatments included in NMA. Figure 3. Risk of bias of included trials. ● Chronic constipation (CC), including functional constipation, irritable bowel CC Naloxegol 12.5Naloxegol mg 5 mg IBS-C syndrome with constipation (IBS-C), and opioid-induced constipation (OIC), Naloxegol 25 mg OIC [12w] [4w] [12w] 1 Naloxegol[4w, 50 12w] mg [12w] [3w, 12w] CC and IBS-C negatively affects patients’ quality of life and has a prevalence rate of [3w, 12w]Alvimopan 0.5 mg [12w] Random sequence generation Alvimopan 1 mg Methylnaltrexone 450 mg 2,3 [4w] Methylnaltrexone 300 mg CC and OIC (selection bias) approximately 14% and 28% worldwide and in Japan, respectively. Methylnaltrexone 150 mg Lactitol[2w] 20 g Naloxone 2.5 mg Lactitol[7d] 10 g Allocation concealment ● The most commonly recommended treatments are polyethylene glycol [3w] Wheat (triticum) 20 g (selection bias) Naloxone 5 mg [4w] (PEG), lubiprostone, linaclotide, prucalopride, lactulose, bisacodyl, and [3w] Naloxone 10 mg Ispaghula 20 g 4 [4w] Blinding of participants and personnel [3w] Ispaghula 10.8 g dietary fibre ; in Japan, magnesium oxide followed by stimulant laxatives Naloxone 20 mg [14d] (performance bias) [3w] 5 Bisacodyl 10 mg are commonly used.
    [Show full text]
  • 2015.09 IBS Drug Class Review.Pdf
    Drug Class Review Agents Indicated in the Treatment of Irritable Bowel Syndrome 56:92 GI Drugs, Miscellaneous Alosetron (Lotronex®) Eluxadoline (Viberzi®) Linaclotide (Linzess®) Lubiprostone (Amitiza®) Tegaserod (Zelnorm®) Final Report September 2015 Review prepared by: Melissa Archer, PharmD, Clinical Pharmacist Irene Pan, PharmD Candidate 2016 Chelsey Hancock, PharmD Candidate 2016 Carin Steinvoort, PharmD, Clinical Pharmacist Gary Oderda, PharmD, MPH, Professor University of Utah College of Pharmacy Copyright © 2015 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved. 1 Table of Contents Executive Summary ......................................................................................................................... 3 Introduction .................................................................................................................................... 4 Table 1. Comparison of the Agents Indicated in the Treatment of IBS ................................. 5 Disease Overview ........................................................................................................................ 6 Table 2. Summary of IBS Treatment Options ........................................................................ 8 Table 3. IBS Disease Staging System .................................................................................... 11 Table 4. Most Current Clinical Practice Guidelines for the Treatment of IBS ..................... 13 Pharmacology ..............................................................................................................................
    [Show full text]
  • Advice Concerning the Addition of Certain Pharmaceutical Products
    U.S. International Trade Commission COMMISSIONERS Daniel R. Pearson, Chairman Shara L. Aranoff, Vice Chairman Jennifer A. Hillman Stephen Koplan Deanna Tanner Okun Charlotte R. Lane Robert A. Rogowsky Director of Operations Karen Laney-Cummings Director of Industries Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Advice Concerning the Addition of Certain Pharmaceutical Products and Chemical Intermediates to the Pharmaceutical Appendix to the Harmonized Tariff Schedule of the United States Investigation No. 332--476 Publication 3883 September 2006 This report was prepared principally by Office of Industries Philip Stone, Project Leader With assistance from Elizabeth R. Nesbitt Primary Reviewers David G. Michels, Office of Tariff Affairs and Trde Agreements, John Benedetto, and Nannette Christ, Office of Economics Administrative Support Brenda F. Carroll Under the direction of Dennis Rapkins, Chief Chemicals and Textiles Division ABSTRACT Under the Pharmaceutical Zero-for-Zero Initiative, which entered into force in 1995, the United States and its major trading partners eliminated tariffs on many pharmaceuticals, their derivatives, and certain chemical intermediates used to make pharmaceuticals. The U.S. list of pharmaceutical products and chemical intermediates eligible for duty-free treatment under the agreement is given in the Pharmaceutical Appendix to the Harmonized Tariff Schedule of the United States. The Pharmaceutical Appendix is periodically updated to provide duty relief for additional such products, including newly developed pharmaceuticals. This report provides advice on the third update to the agreement, in which approximately 1,300 products are proposed to receive duty-free treatment.
    [Show full text]
  • Draft Guidance on Linaclotide Active Ingredient
    Contains Nonbinding Recommendations Draft Guidance on Linaclotide This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the Office of Generic Drugs. Active Ingredient: Linaclotide Dosage Form; Route: Capsule; Oral Strength: 72 mcg, 145 mcg and 290 mcg Overview: This draft guidance provides recommendations for the development of generic drug product, Linaclotide Capsule, using synthetic linaclotide as the active pharmaceutical ingredient (API). First, FDA provides recommendations for characterizations to support a demonstration of API sameness. Second, FDA provides recommendations for demonstrating bioequivalence (BE) of this product. Third, FDA provides recommendations for in vitro nasogastric (NG) or gastrostomy (G) tube comparative studies. Recommendations for Demonstrating API Sameness: Sameness of synthetic linaclotide can be established based on comparative physico-chemical and biological characterizations. The characterizations should include the following categories in order to support API sameness: 1. Primary peptide sequence and related molecular properties such as molecular formula, specific optical rotation, and spectroscopic properties 2. Configuration of the three disulfide bonds 3. In vitro biological activity (e.g., binding, functional assays) Recommendations for Demonstrating BE: Two options: In vitro and in vivo options 1. In vitro option If the test product formulations are qualitatively (Q1) and quantitatively (Q2) the same as the reference listed drug (RLD)1 in terms of inactive ingredients for the corresponding strength, then bioequivalence (BE) of that strength may be established based solely on comparative dissolution.
    [Show full text]