NCT01279590已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 282
- 试验地点
- 3
- 主要终点
- Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosis of primary hypercholesterolemia (heterozygous familial and nonfamilial) Fredrickson types IIa or IIb.
- •history of statin-associated myalgia, as defined by being unable to tolerate two previous statins due to muscle pain, aches, weakness, or cramping that begins or increases during statin therapy and stops when statin therapy is discontinued. History of statin-associated myalgia will be captured on the historical questionnaire on statin-associated myalgia.
- •LDL-C > 110 mg/dL and triglycerides < 500 mg/dL at Prescreening.
- •prescreening hemoglobin value of ≥10 g/dL for females and ≥12 g/dL.
- •patient agrees to stop all other antihyperlipidemic agents (including but not limited to niacin, probucol, ezetimibe, fibrates and derivatives, bile acid-sequestering agents, other 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA) reductase inhibitors, fish oils, flaxseed oil, and red yeast rice).
- •patient agrees to stop all Coenzyme Q10 supplements.
- •if taking other nonexcluded medications, patients must be on a stable dose for 4 weeks before screening.
排除标准
- •history of chronic pain and currently experiences chronic pain unrelated to statins that requires chronic use of pain medications, has been diagnosed with fibromyalgia or has severe neuropathic pain.
- •requires the chronic use of pain medications, including acetaminophen, non-steroidal anti-inflammatory medications, narcotics, and other analgesics.
- •vitamin D insufficiency (current insufficiency is defined as Vitamin D3 < 20 ng/mL [50 nmol/L] measured at Prescreening.
- •hypothyroidism or abnormal thyroid function test as confirmed by thyroid-stimulating hormone ≥ 5 mcIU/mL and free thyroxine (T4) < 0.7 ng/dL at Prescreening
- •history of rhabdomyolysis (defined as evidence of organ damage with creatinine kinase(CK) > 10,000 IU/L).
- •history of liver disease
- •history of significant renal dysfunction as defined by serum creatinine clearance < 30 mL/min
- •Nephrotic-range proteinuria.
- •HbA1C >9% at Prescreening.
- •CK levels >5 times the upper limit of normal at Prescreening.
- •congestive heart failure, even with current therapy
- •has had myocardial infarction, cardiac intervention, cerebrovascular accident/stroke or transient ischemic attack less than 6 months prior to prescreening.
- •patient is pregnant (confirmed by laboratory testing) or breastfeeding.
- •history of cancer (other than basal cell and/or squamous cell carcinoma of the skin and/or Stage I squamous cell carcinoma of the cervix) that has not been in full remission for at least 1 year before Screening.
- •patient has positive test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus types 1 or 2 at Prescreening.
研究组 & 干预措施
PPD10558
Experimental
Dosing will be forced-titrated as follows: 40 mg orally twice daily for 4 weeks and 80 mg orally twice daily for 8 weeks
干预措施: PPD10558 (Drug)
Atorvastatin
Active Comparator
Dosing will be forced titrated as 40 mg orally once daily for 4 weeks, and 80 mg orally once daily for 8 weeks
干预措施: Atorvastatin (Drug)
Placebo
Placebo Comparator
Dosing will be 2 placebo capsules twice daily for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia.
时间窗: Up to week 12
Patients who withdraw from participating in the study prior to Week 12 and who also stop study drug due to SAM, or patients who become lost to follow up will be considered to have stopped treatment with double-blinded study drug.
次要结局
- Change from Baseline in fasting lipid profile components (low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), triglyceride(TG), total cholesterol(TC), Apolipoprotein B(ApoB), HDL-TG, LDL/HDL ratio and TC/HDL ratio)(Up to week 12)
- Change from baseline in muscle strength measurements (Sit-to-stand(STS) performance and hand grip strength by Jamar Hydraulic Hand Dynamometer)(Up to week 12)
- Frequency of pain rescue medication(Up to week 12)
- Change from Baseline in inflammatory markers (Tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2))(Up to week 12)
- Change in patients' functional health and well-being as measured by the Short Form-36v2 Health Survey (SF-36)(Up to week 12)
- Time to onset of statin -associated myalgia (SAM)(Up to week 12)
- Time to stopping treatment with study drug due to SAM(Up to week 12)
研究者
研究点 (3)
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