Study of the Safety and Tolerability Associated With PPD10558 Versus Atorvastatin in Patients Previously Intolerant to Statins Due to Statin-associated Myalgia (SAM)

Phase 2

Completed

Conditions: Myalgia
Hypercholesterolemia
Hyperlipidemia

Interventions: Drug: PPD10558
Drug: Atorvastatin
Drug: Placebo

Registration Number: NCT01279590

Lead Sponsor: Furiex Pharmaceuticals, Inc

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 282

Inclusion Criteria

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.

Exclusion Criteria

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PPD10558	PPD10558	Dosing will be forced-titrated as follows: 40 mg orally twice daily for 4 weeks and 80 mg orally twice daily for 8 weeks
Atorvastatin	Atorvastatin	Dosing will be forced titrated as 40 mg orally once daily for 4 weeks, and 80 mg orally once daily for 8 weeks
Placebo	Placebo	Dosing will be 2 placebo capsules twice daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia.	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.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3): Furiex research site
🇺🇸
Richmond, Virginia, United States
Furiex
🇺🇸
Spokane, Washington, United States
Furiex Research site
🇺🇸
Boise, Idaho, United States