DOCSLIB.ORG

Summary Results

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Summary Results The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall potential risks or benefits of a product which are based on an evaluation of an entire research program. Before prescribing any Takeda products, healthcare professionals should consult prescribing information for the product approved in their country. TAK 475 EC302 CSR 23rd October 2007 SYNOPSIS Title of Study: A Placebo-Controlled, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 50 mg and 100 mg Versus Placebo, When Coadministered With Simvastatin 20 mg or 40 mg in Subjects With Primary Dyslipidemia Name of Sponsor: Takeda Global Research & Development Centre (Europe) Ltd. Name of Active Ingredient: Lapaquistat acetate Name of Finished Product: Not applicable Investigators/Study Centers: 81 sites in 7 countries (Europe and South Africa) Publication: None Study Period: Phase of Development: 22 October 2005 to 01 March 2007 Phase 3 OBJECTIVES Primary: The primary objective of this study was to evaluate the reduction in low-density lipoprotein cholesterol (LDL-C) in subjects with primary dyslipidemia when treated with lapaquistat acetate 50 mg once daily (QD), lapaquistat acetate 100 mg QD, or placebo when coadministered with simvastatin 20 or 40 mg QD for 24 weeks. Secondary: The secondary objectives of this study were to evaluate the effects of lapaquistat acetate 50 mg QD, lapaquistat acetate 100 mg QD, or placebo when coadministered with simvastatin 20 or 40 mg QD for 24 weeks on • other lipid variables; • high-sensitivity C-reactive protein (hs-CRP); • the overall safety and tolerability during and after 24 weeks of treatment; • the percentage of subjects who achieved LDL-C concentrations of <1.813, 2.590, and 3.367 mmol/L (<70, 100, 130 mg/dL) at the Final Visit; and • plasma concentration-time profile of lapaquistat acetate, M-I, and M-II. An additional secondary objective was to identify subject factors (covariates) that affected the apparent clearance of the drug. METHODOLOGY This was a phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study designed to evaluate the efficacy and safety of lapaquistat acetate 50 mg or 100 mg coadministered with a stable dose of simvastatin (20 or 40 mg) compared with simvastatin monotherapy for 24 weeks in subjects with primary dyslipidemia. Subjects who had been taking a previously prescribed dose of simvastatin (20 or 40 mg) for at least 4 weeks and who initially met study eligibility criteria entered a 4-week diet stabilization period (on the therapeutic lifestyle change diet) and returned to the site at Weeks -2 and -1 for repeat qualifying lipid tests. TAK 475 EC302 CSR 23rd October 2007 Title of Study: A Placebo-Controlled, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 50 mg and 100 mg Versus Placebo, When Coadministered With Simvastatin 20 mg or 40 mg in Subjects With Primary Dyslipidemia Qualifying subjects were randomized to treatment after stratification on the basis of the subject’s simvastatin dose (20 or 40 mg) and Baseline triglyceride (TG) level (1.695 or >1.695 mmol/L [150 or >150 mg/dL]). Subjects self- administered study drug (lapaquistat acetate 50 mg QD, lapaquistat acetate 100 mg QD, or matching placebo) from Weeks 1 through 24 and returned to the site at Weeks 2, 4, 8, 12, 16, 20, and 24 for study procedures. Number of Subjects: Planned: 522 subjects in a 1:1:1 ratio (174 in each treatment group). Analyzed: 517 Diagnosis and Main Criteria for Inclusion: To be eligible for study participation, subjects were required to be men or women, 18 years of age or older with documented stable primary dyslipidemia (within 4 weeks of Screening), who had elevated LDL-C 100 to 190 mg/dL (2.59 to 4.92 mmol/L) and mean TG levels 400 mg/dL (4.5 mmol/L) within the 6 months prior to Screening (Visit 1). In addition, it was required that subjects be on a stable dose of simvastatin (either 20 or 40 mg) for at least 4 weeks prior to Screening. In order to be randomized, subjects were required to have mean LDL-C levels 100 to 170 mg/dL (2.59 to 4.40 mmol/L) and mean TG levels 400 mg/dL (4.5 mmol/L), based on calculations made from measurements at Visit 2 (Week -2) and Visit 3 (Week -1). To be randomized, for each subject the difference between the 2 individual values was not to differ by more than 15% of the upper value for LDL-C, and the upper value for TG (for either sample) was to be 450 mg/dL (5.1 mmol/L). Test Product Dose and Mode of Administration Lot Numbers Lapaquistat acetate 100 mg tablet, oral, QD Z5537111 Lapaquistat acetate 50 mg tablet, oral, QD Z553B031 Matching placebo Z5535071 Duration of Treatment: This study comprised a 4 (+1)-week Run-in Period followed by a 24-week treatment period (ie, approximately 29 weeks). Criteria for Evaluation: Efficacy: The primary efficacy variable was fasting plasma LDL-C concentration based on direct measurement. The secondary efficacy variables were the fasting plasma concentrations of calculated LDL-C, non–high-density lipoprotein cholesterol (non–HDL-C) (derived as total cholesterol [TC] minus HDL-C), TC, apolipoprotein B (Apo B), TG, HDL-C, apolipoprotein A1 (Apo A1), very-low-density lipoprotein cholesterol (VLDL-C), derived ratios (LDL-C/HDL-C, TC/HDL-C, and Apo B/Apo A1), and hs-CRP. Safety: Safety variables included adverse events, clinical laboratory results (chemistry, hematology, and urinalysis), physical examination findings, electrocardiogram (ECG) assessments, best corrected visual acuity (BCVA) results, and vital signs. TAK 475 EC302 CSR 23rd October 2007 Title of Study: A Placebo-Controlled, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 50 mg and 100 mg Versus Placebo, When Coadministered With Simvastatin 20 mg or 40 mg in Subjects With Primary Dyslipidemia Statistical Methods: All statistical analyses were based on the statistical analysis plan, which was finalized before unblinding. The primary efficacy analysis was based on the percent change from Baseline to Week 24 (or time of early withdrawal) in direct fasting plasma LDL-C value. Treatment groups were compared using an analysis of covariance (ANCOVA) model with treatment as factor and Baseline value as covariate. To control the type 1 error in the primary analysis, a step-wise procedure was employed. If the P-value for lapaquistat acetate 100 mg vs placebo was not statistically significant at the 0.05 level, then the comparison of lapaquistat acetate 50 mg with placebo was not needed. However, if the P-value was statistically significant at the 0.05 level, the P-value for lapaquistat acetate 50 mg vs placebo was examined. Secondary variables were analyzed using the same analysis model as the primary analysis. For time-effect displays, primary and secondary variables were summarized and analyzed by study visit. ANCOVA models similar to the model used in the primary analysis were used in these analyses. For TG, the assumption of normality was assessed using the Shapiro-Wilk statistic. If the assumptions were found not to hold, a nonparametric analysis based on the Wilcoxon Rank-Sum test was used to corroborate or supersede the parametric analysis. The estimate of treatment differences in median and 95% confidence intervals (CIs) was based on the Hodges-Lehmann method and the distribution-free CI, respectively. The proportions of subjects who achieved LDL-C concentrations of less than 1.813, 2.590, and 3.367 mmol/L (<70, 100, and 130 mg/dL) at Week 24 (or time of early withdrawal) were summarized in a shift table; no formal statistical analysis was performed. To control the type 1 error across all efficacy variables intended to be included in the labeling, the efficacy variables were summarized and analyzed in the following order: direct LDL-C, non–HDL-C, TC, Apo B, TG, and HDL-C. If a variable in this sequence was not statistically significant at the alpha level of 0.05, the testing procedure was stopped for the subsequent variables. The number of subjects who reached the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) LDL-C goals at Week 24 (or Early Termination) were analyzed using a logistic regression model with terms for treatment, NCEP ATP III risk category (three levels based on the target LDL-C goals), and baseline LDL-C. A similar analysis was also performed for those subjects who were not at their LDL-C goal at Baseline. Summary statistics including P-values, estimates of odds-ratios, and 95% CI for the odds-ratio were presented. In the safety analyses, adverse events were coded using the Medical Dictionary for Regulatory Activities (Version 8.1) and summarized using descriptive statistics. Clinical laboratory test results were summarized descriptively by treatment. Markedly abnormal laboratory values were summarized by treatment group, including the number and percentage of subjects in each laboratory parameter group. Shift tables were produced that included the number of subjects per group with low, normal, or high values with respect to the reference ranges, and the number and percentage of subjects in each shift combination. Descriptive statistics of vital signs, ECG intervals, and BCVA evaluations were produced for each treatment group. SUMMARY OF RESULTS Subject Disposition: A total of 449 subjects completed the study. Within the placebo, lapaquistat acetate 50 mg, and lapaquistat acetate 100 mg groups, 13.6%, 11.0%, and 17.2% of subjects, respectively, discontinued from the study. Both overall and within each treatment group, the most common reasons for discontinuation were adverse events (30 subjects overall) and voluntary withdrawal (23 subjects overall); 1 placebo-treated subject withdrew due to pregnancy.
Load more

Recommended publications
  • Stems for Nonproprietary Drug Names
    USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol
    [Show full text]
  • Kevin C Maki CV 20June2019
    Kevin C. Maki, PhD, CLS, FNLA, FTOS, FACN Tel: 630-469-6600; Fax: 773-980-7151 Administrative Office Chicago Research Clinic Boca Raton Research Clinic Midwest Biomedical Great Lakes Clinical Trials MB Clinical Research Research 5149 North Ashland Ave. 751 Park of Commerce Drive 211 East Lake Street Chicago, Illinois 60640 Suite 118 Suite 3 Co-located with Great Boca Raton, Florida 33487 Addison, Illinois 60101 Lakes Clinical Trials E-MAIL: [email protected] [email protected] ACADEMIC & PROFESSIONAL EXPERIENCE: 2013-Present President and Chief Scientist MB Clinical Research and Consulting, LLC [MBClinicalResearch.com] Divisions: • Midwest Biomedical Research: Center for Metabolic & Cardiovascular Health, Addison, Illinois • MB Clinical Research Boca Raton, Florida 2014-Present Investigator Great Lakes Clinical Trials Chicago, Illinois 2013-Present Adjunct Faculty, Epidemiology and Biostatistics DePaul University, Department of Nursing Chicago, Illinois 2016-2018 Adjunct Faculty, Epidemiology and Biostatistics Illinois Institute of Technology Department of Food Science and Nutrition Chicago, Illinois 2004-2013 Chief Science Officer Biofortis Clinical Research (Formerly Provident Clinical Research) Addison, Illinois 2003-2004 Chief Science Officer Radiant Development (Formerly Protocare Development) Chicago, Illinois 2002-2003 Senior Vice President and Chief Science Officer Protocare Development, Inc. Chicago, Illinois 2000-2002 Vice President Protocare Development, Inc. Chicago, Illinois Kevin C. Maki, Ph.D. – Curriculum Vitae
    [Show full text]
  • CURRENT MEDICAL CHEMISTRY Repositioning of TAK-475 in Mevalonate Kinase Disease: Translating Theory Into Practice
    CURRENT MEDICAL CHEMISTRY Repositioning of TAK-475 in Mevalonate Kinase Disease: translating theory into practice Annalisa Marcuzzia, Claudia Loganesb, Claudio Celeghinic, Giulio Kleinerd,* a Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy. b Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy c Department of Life Sciences, University of Trieste, Trieste, Italy. d Department of Neurology, Columbia University Medical Center, New York, NY, USA *Address correspondence to this author at the Department of Neurology, Columbia University Medical Center, New York, NY, USA. Tel/Fax: 212-305-1637 E-mail: [email protected] Abstract Mevalonate Kinase Deficiency (MKD, OMIM #610377) is a rare autosomal recessive metabolic and inflammatory disease. In MKD, defective function of the enzyme mevalonate kinase (MK) due to mutation in the MVK gene, leads to the shortage of mevalonate-derived intermediates, which results in unbalanced prenylation of proteins and altered metabolism of sterols. These defects are reflected in a complex multisystemic inflammatory and metabolic syndrome. Although biologic therapies blocking the pro-inflammatory cytokine interleukin -1, can significantly reduce inflammation, they cannot completely control the clinical symptoms, in particular those affecting the nervous system. For this reason, MKD has been designed as an orphan drug disease. Of note, zaragozic acid, an inhibitor of squalene synthase, has been proven to inhibit the hyper-inflammatory response in cellular models of MKD, by diverting mevalonate intermediates toward geranylgeranylation rather than to the synthesis of squalene. A similar action might be obtained by Lapaquistat (TAK-475, Takeda), a drug that underwent extensive clinical trials as cholesterol lowering agent 10 years ago with a good safety profile.
    [Show full text]
  • A Chemical Biology Screen Identifies a Vulnerability of Neuroendocrine
    ARTICLE https://doi.org/10.1038/s41467-018-07959-4 OPEN A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition Christopher E. Mahoney 1, David Pirman1, Victor Chubukov1, Taryn Sleger1, Sebastian Hayes 1, Zi Peng Fan1, Eric L. Allen1, Ying Chen2, Lingling Huang2, Meina Liu2, Yingjia Zhang2, Gabrielle McDonald1, Rohini Narayanaswamy1, Sung Choe1, Yue Chen1, Stefan Gross 1, Giovanni Cianchetta1, Anil K. Padyana1, Stuart Murray1, Wei Liu1, Kevin M. Marks1, Joshua Murtie1, Marion Dorsch1, Shengfang Jin1, Nelamangala Nagaraja1, Scott A. Biller1, Thomas Roddy1, Janeta Popovici-Muller1,3 & Gromoslaw A. Smolen 1,4 1234567890():,; Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epox- idase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers. 1 Agios Pharmaceuticals, 88 Sidney Street, Cambridge, MA 02139, USA. 2 Shanghai ChemPartner Co. Ltd., 998 Halei Road, Pudong, 201203 Shanghai, China. 3Present address: Decibel Therapeutics, 1325 Boylston Street, Suite 500, Boston, MA 02215, USA. 4Present address: Celsius Therapeutics, 215 First Street, Cambridge, MA 02142, USA. Correspondence and requests for materials should be addressed to G.A.S.
    [Show full text]
  • Summary Results
    The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall potential risks or benefits of a product which are based on an evaluation of an entire research program. Before prescribing any Takeda products, healthcare professionals should consult prescribing information for the product approved in their country. 7$.(& 2FWREHU 6<1236,6 7LWOHRI6WXG\ A Placebo-Controlled, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 100 mg in Subjects With Type 2 Diabetes Currently Treated With Lipid-Lowering Therapy 1DPHRI6SRQVRU Takeda Global Research & Development Centre (Europe) Ltd. 1DPHRI$FWLYH,QJUHGLHQW Lapaquistat acetate 1DPHRI)LQLVKHG3URGXFW Not applicable ,QYHVWLJDWRUV6WXG\&HQWHUV 121 sites in Europe, South Africa, and the United States 3XEOLFDWLRQ None 6WXG\3HULRG 3KDVHRI'HYHORSPHQW 05 December 2005 to 09 May 2007 Phase 3 2%-(&7,9(6 3ULPDU\ The primary objective of this study was to evaluate the efficacy of lapaquistat acetate compared with placebo on low-density lipoprotein cholesterol (LDL-C) levels in subjects with type 2 diabetes currently treated with optimal doses of other lipid-lowering drugs. 6HFRQGDU\ The secondary objectives of this study were to evaluate the following: • Safety and tolerability (treatment-emergent adverse events [TEAEs], safety laboratory test results, physical examination findings, best corrected visual acuity [BCVA] results, electrocardiogram [ECG] assessments, vital signs, and weight). • Changes in secondary lipid variables (calculated LDL-C, non–high-density lipoprotein cholesterol [non-HDL-C], total cholesterol [TC], apolipoprotein B [Apo B], triglycerides [TG], HDL-C, apolipoprotein A1 [Apo A1], very–low-density lipoprotein cholesterol [VLDL-C], and other derived lipid variables [LDL-C/HDL-C, TC/HDL-C, and Apo B/Apo A1]).
    [Show full text]
  • 2 12/ 35 74Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 22 March 2012 (22.03.2012) 2 12/ 35 74 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/16 (2006.01) A61K 9/51 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/065959 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 September 201 1 (14.09.201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/382,653 14 September 2010 (14.09.2010) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, NANOLOGICA AB [SE/SE]; P.O Box 8182, S-104 20 ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Stockholm (SE).
    [Show full text]
  • Screening for Dyslipidemia in Younger Adults: Systematic Review to Update the 2008 U.S
    Evidence Synthesis Number 138 Screening for Dyslipidemia in Younger Adults: Systematic Review to Update the 2008 U.S. Preventive Services Task Force Recommendation Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract No. HHSA-290-2012-00015-I, Task Order No. 2 Prepared by: Pacific Northwest Evidence-Based Practice Center Oregon Health & Science University 3181 SW Sam Jackson Park Road Portland, OR 97239 www.ohsu.edu/epc Investigators: Roger Chou, MD, FACP Tracy Dana, MLS Ian Blazina, MPH Monica Daeges, BA Christina Bougatsos, MPH Thomas Jeanne, MD AHRQ Publication No. 14-05206-EF-1 December 2015 This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2012-00015-I, Task Order No. 2). The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information (i.e., in the context of available resources and circumstances presented by individual patients).
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • Lipid Therapeutics Update - Going Above and Beyond Statin Therapy
    Lipid therapeutics update - going above and beyond statin therapy Prof. Anthony S. Wierzbicki Consultant in Metabolic Medicine/Chemical Pathology Guy’ & St. Thomas’ Hospitals London SE1 7EH, UK Changing epidemiology of diabetes Type 1 diabetes Type 2 diabetes • Autoimmune disease • Obesity • Childhood-onset disease • T2DM at age> 40 • E.g. GAD Ab (+) • Atherogenic lipid profile • ‘Normal’ lipid profile • Low HDL-C; high TG; sdLDL • Obesity • Autoimmune disease • Increased childhood • Adult-onset disease obesity • GAD Ab (+); HLA-DQ group • T2DM at age 12-20 Basile KJ et al; Curr Diab Rep 2014; 14: 550; Zeitler JC; JCEM 2010; 95 : 5163 Problems with calculated LDL-C: Lipid efficacy: switch to non-HDL-C • LDL-C Friedewald • Poor calibration • Little DM data • cLDL-C on-treatment error • Non-HDL-C better for CVD risk • NHS Health Check • Move to HbA1c for DM • GP workload pressure N=1,350908 Rabar S et al; BMJ 2014 & Martin S et al; JAMA 2013; 310 : 2061 Meta-analyses of CHD vs LDL-C and Incremental effects of lipid drugs Cholesterol Treatment Trialists; Lancet 2010; 376: 1670 Charland SL & Stanek EJ; Pharmacother 2014; 34 : 452 All Prevention: Is lower better? (in 2009) 4S-P 25 Secondary prevention Primary prevention 20 Lipid-P 4S-Rx 15 CARE-Rx CARE-P HPS-P WOS-P 10 Lipid-Rx TnT-Px AFCAPS-P CHD event rate (%) rate event CHD HPS-Rx TnT-P 5 AFCAPS-Rx JUPITER-Rx JUPITER-P WOS-Rx ASCOT-Rx ASCOT-P 0 1.3 1.8 2.3 2.8 3.3 3.8 4.3 4.8 5.3 LDL-Cholesterol (mmol/L) Modified from Kastelein JJP.
    [Show full text]
  • Kevin C Maki CV 24Aug2021
    Kevin C. Maki, PhD, CLS, FNLA, FTOS, FACN Tel: 630-469-6600; Fax: 773-980-7151 Administrative Office Chicago Research Clinic Boca Raton Office Midwest Biomedical Research Great Lakes Clinical Trials MB Clinical Research 211 East Lake St, Ste 3 5149 North Ashland Ave 950 Peninsula Cir, Ste 2019 Addison, Illinois 60101 Chicago, Illinois 60640 Boca Raton, Florida 33487 E-MAIL: [email protected] [email protected] ACADEMIC & PROFESSIONAL EXPERIENCE: 2013-Present President and Chief Scientist MB Clinical Research and Consulting, LLC; Divisions: • Midwest Biomedical Research; Addison, Illinois • MB Clinical Research, Boca Raton, Florida 2014-Present Investigator/Managing Member Great Lakes Clinical Trials Chicago, Illinois 2019-Present Adjunct Professor and Dean’s Eminent Scholar Indiana University Department of Applied Health Science School of Public Health Bloomington, Indiana 2013-2019 Adjunct Faculty, Epidemiology and Biostatistics DePaul University College of Science and Health Chicago, Illinois 2016-2018 Adjunct Faculty, Epidemiology and Biostatistics Illinois Institute of Technology Department of Food Science and Nutrition Chicago, Illinois 2004-2013 Chief Science Officer Biofortis Clinical Research (Formerly Provident Clinical Research) Addison, Illinois 2003-2004 Chief Science Officer Radiant Development (Formerly Protocare Development) Chicago, Illinois 2002-2003 Senior Vice President and Chief Science Officer Protocare Development, Inc. Chicago, Illinois Kevin C. Maki, Ph.D. – Curriculum Vitae Page 2 2000-2002 Vice President Protocare Development, Inc. Chicago, Illinois 1998-2000 Director, Nutrition and Metabolism Research Unit Chicago Center for Clinical Research/Protocare, Inc. Chicago, Illinois 1995-1998 Director, Biostatistics and Medical Writing Chicago Center for Clinical Research/Protocare, Inc. Chicago, Illinois 1991-1995 Research Health Scientist Rehabilitation Research and Development Center Edward Hines, Jr.
    [Show full text]
  • A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor S
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2017/03/30/jpet.116.239574.DC1 1521-0103/361/3/417–428$25.00 https://doi.org/10.1124/jpet.116.239574 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 361:417–428, June 2017 Copyright ª 2017 by The Author(s) This is an open access article distributed under the CC BY Attribution 4.0 International license. A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor s Alastair G. Kerr, Lawrence C. S. Tam, Ashley B. Hale, Milena Cioroch, Gillian Douglas, Sarina Agkatsev, Olivia Hibbitt, Joseph Mason, James Holt-Martyn, Carole J. R. Bataille, Graham M. Wynne, Keith M. Channon, Angela J. Russell, and Richard Wade-Martins Departments of Physiology, Anatomy, and Genetics (A.G.K., L.C.S.T., M.C., S.A., O.H., J.H.-M., R.W.-M.) and Pharmacology (A.J.R.), University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (A.B.H., G.D., K.M.C.); and Chemistry Research Downloaded from Laboratory,DepartmentofChemistry,UniversityofOxford,Oxford,UnitedKingdom(J.M.,C.J.R.B.,G.M.W.,A.J.R.) Received December 14, 2016; accepted March 6, 2017 ABSTRACT Hypercholesterolemia remains one of the leading risk factors for the and human liver cell lines at nanomolar potencies (EC50 5 39 nM). jpet.aspetjournals.org development of cardiovascular disease.
    [Show full text]