A Double-blind, Randomized, Placebo-controlled and Active-comparator-controlled Phase 2b Study to Evaluate Statin-associated Myalgia Incidence, Lipid Profile Effect, and Safety and Tolerability Associated With PPD10558 Versus Atorvastatin in Patients With Primary Hypercholesterolemia, Fredrickson IIa or IIb, Who Have Discontinued Two or More Prior Statin Therapies Due to Statin-associated Myalgia

The purpose of this study is to assess the incidence of statin-associated myalgia (SAM) with treatment with PPD10558 versus atorvastatin in patients previously intolerant to statins.
To assess the safety and tolerability of PPD10558 compared to atorvastatin in patients previously intolerant to statins.

开始日期2011-03-01

申办/合作机构

Furiex Pharmaceuticals, Inc.

100 项与 Bemfivastatin 相关的临床结果

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100 项与 Bemfivastatin 相关的转化医学

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100 项与 Bemfivastatin 相关的专利（医药）

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项与 Bemfivastatin 相关的文献（医药）

2012-02-01·Birth Defects Research Part B: Developmental and Reproductive Toxicology

Developmental Toxicity of the HMG‐CoA Reductase Inhibitor (PPD10558) in Rats and Rabbits

Article

作者: Rocio Lopez ; Gail McIntyre ; David Prohaska ; Ali S. Faqi

PPD10558 is an orally active, lipid‐lowering 3–hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor (statin) being developed as a treatment for hypercholesterolemia in patients who have not been able to tolerate statins because of statin‐associated myalgia. We have studied the potential developmental toxicity effects of PPD10558 in pregnant rats and rabbits given daily oral doses during the period of organogenesis. Rats were dosed with 0, 20, 80, or 320 mg/kg/day from Gestation Day (GD) 6 to 17 and rabbits received dose levels of 0, 12.5, 25, or 50 mg/kg/day from GD 6 to 18. Additional groups in both studies served as toxicokinetic animals and received the PPD10558 in the same manner as the main study groups at the same dose levels. Blood samples were collected from toxicokinetic animals at designated time points on GD 6 and 17 in rats and GD 6 and 18 in rabbits. Fetal exposure in rats was assessed on GD 20. Maternal and developmental parameters were evaluated in rats and rabbits on GD 20 and GD 29, respectively. No maternal and developmental toxicity was observed at any of the dose levels used in the rat study. Evidence of fetal exposure was determined in fetal plasma with mean fetal concentrations of PPD10558 and the metabolite (PPD11901) found to be between 1 and 6% of the mean maternal concentrations. In rabbits, marked maternal toxicity including mortality (eight deaths; 1 dose at 25 and 7 at 50 mg/kg/day), abortions (2 at 25 mg/kg/day and 6 at 50 mg/kg/day) and reduction in gestation body weight, gestation body weight changes and decreased food consumption were observed. In addition, fetal body weights of the combined sexes were significantly reduced at 50 mg/kg/day in comparison with the controls. Mean peak exposure (Cmax) and total exposure (AUC(0–24)) of PPD11901 in both rats and rabbits were higher than that of PPD10558 on GD 6 and GD 17 at each of the three dose levels.. Based on the results of these studies, the no observed adverse effect level (NOAEL) for maternal and developmental toxicity in rats was considered to be ≥320 mg/kg/day, the highest dose level used in the study. The NOAEL for maternal and developmental toxicity in rabbits was 12.5 mg/kg/day and 25 mg/kg/day, respectively.

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肌痛	临床2期	美国	Furiex Pharmaceuticals, Inc.	2011-03-01
原发性高胆固醇血症	临床2期	美国	Furiex Pharmaceuticals, Inc.	2011-03-01
SAM综合征	临床2期	美国	Furiex Pharmaceuticals, Inc.	2011-03-01