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

Furiex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Myalgia; Hyperlipidemia; Hypercholesterolemia

Treatments: Drug: Atorvastatin; Drug: PPD10558; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01279590

PPD10558-010

Details and patient eligibility

About

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.

Enrollment: 282 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

282 participants in 3 patient groups, including a placebo group

PPD10558

Experimental group

Description:

Dosing will be forced-titrated as follows: 40 mg orally twice daily for 4 weeks and 80 mg orally twice daily for 8 weeks

Treatment:

Drug: PPD10558

Atorvastatin

Active Comparator group

Description:

Dosing will be forced titrated as 40 mg orally once daily for 4 weeks, and 80 mg orally once daily for 8 weeks

Treatment:

Drug: Atorvastatin

Placebo

Placebo Comparator group

Description:

Dosing will be 2 placebo capsules twice daily for 12 weeks

Treatment:

Drug: Placebo