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

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01279590
• Other study ID #: PPD10558-010
• Status: Completed
• Phase: Phase 2
• First received: January 18, 2011
• Last updated: December 19, 2011
• Start date: March 2011
• Est. completion date: November 2011

Study information

• Verified date: December 2011
• Source: Furiex Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hyperlipidemia
• Hyperlipidemias
• Myalgia

Intervention

Drug:
• PPD10558
PPD10558 40 mg capsule and matching placebo capsule twice a day for 4 weeks, then PPD10558 80 mg (two 40 mg capsules) twice a day for 8 weeks
• Atorvastatin
Atorvastatin 40 mg capsule and matching placebo capsule in the morning and 2 placebo capsules in the evening for 4 weeks, then Atorvastatin 80 mg (two 40 mg capsules) in the morning and 2 placebo capsules in the evening for 8 weeks
• Placebo
2 placebo capsules twice daily for 12 weeks

Locations

Country	Name	City	State
United States	Furiex research site	Altoona	Pennsylvania
United States	Furiex research site	Anderson	South Carolina
United States	Furiex research site	Anniston	Alabama
United States	Furiex research site	Asheville	North Carolina
United States	Furiex research site	Auburn	Maine
United States	Furiex research site	Bay City	Michigan
United States	Furiex research site	Billings	Montana
United States	Furiex Research site	Boise	Idaho
United States	Furiex research site	Boynton Beach	Florida
United States	Furiex research site	Bristol	Tennessee
United States	Furiex research site	Butte	Montana
United States	Furiex research site	Carlisle	Ohio
United States	Furiex research site	Cary	North Carolina
United States	Furiex research site	Charlotte	North Carolina
United States	Furiex research site	Chicago	Illinois
United States	Furiex research site	Cincinnati	Ohio
United States	Furiex research site	Colorado Springs	Colorado
United States	Furiex research site	Columbus	Ohio
United States	Furiex research site	Coral Gables	Florida
United States	Furiex research site	Covington	Louisiana
United States	Furiex research site	Cumberland	Rhode Island
United States	Furiex research site	Deerfield Beach	Florida
United States	Furiex research site	East Providence	Rhode Island
United States	Furiex research site	Fort Lauderdale	Florida
United States	Furiex research site	Gainesville	Florida
United States	Furiex research site	Golden	Colorado
United States	Furiex research site	Great Neck	New York
United States	Furiex research site	Greenville	South Carolina
United States	Furiex research site	Greer	South Carolina
United States	Furiex research site	Harrisburg	North Carolina
United States	Furiex research site	Hartford	Connecticut
United States	Furiex research site	Hickory	North Carolina
United States	Furiex research site	Hickory	North Carolina
United States	Furiex research site	High Point	North Carolina
United States	Furiex research site	Honolulu	Hawaii
United States	Furiex research site	Huntington Park	California
United States	Furiex research site	Johnstown	Pennsylvania
United States	Furiex research site	Kettering	Ohio
United States	Furiex research site	Long Beach	California
United States	Furiex research site	Madisonville	Kentucky
United States	Furiex research site	Mission	Kansas
United States	Furiex research site	Missoula	Montana
United States	Furiex research site	Mt. Pleasant	South Carolina
United States	Furiex research site	Nampa	Idaho
United States	Furiex research site	Norfolk	Virginia
United States	Furiex research site	Omaha	Nebraska
United States	Furiex research site	Opa Locka	Florida
United States	Furiex research site	Oxon Hill	Maryland
United States	Furiex research site	Pawley's Island	South Carolina
United States	Furiex research site	Pembroke	Florida
United States	Furiex research site	Pembroke	Florida
United States	Furiex research site	Phoenix	Arizona
United States	Furiex research site	Phoenix	Arizona
United States	Furiex research site	Pismo Beach	California
United States	Furiex research site	Raleigh	North Carolina
United States	Furiex research site	Raleigh	North Carolina
United States	Furiex research site	Richmond	Virginia
United States	Furiex research site	Salt Lake City	Utah
United States	Furiex research site	San Diego	California
United States	Furiex research site	Sanford	Florida
United States	Furiex	Spokane	Washington
United States	Furiex research site	Springfield	Ohio
United States	Furiex research site	St. Louis	Missouri
United States	Furiex research site	Tomball	Texas
United States	Furiex research site	West Lake Village	California
United States	Furiex research site	West Palm Beach	Florida
United States	Furiex research site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Furiex Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia.	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.	Up to week 12	No
Secondary	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	No
Secondary	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	No
Secondary	Frequency of pain rescue medication		Up to week 12	No
Secondary	Change from Baseline in inflammatory markers (Tumor necrosis factor a (TNF-a), C-reactive protein (CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2))		Up to week 12	No
Secondary	Change in patients' functional health and well-being as measured by the Short Form-36v2 Health Survey (SF-36)		Up to week 12	No
Secondary	Time to onset of statin -associated myalgia (SAM)		Up to week 12	No
Secondary	Time to stopping treatment with study drug due to SAM		Up to week 12	No