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

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.

Study Overview

• Status: Completed
• Conditions: Myalgia; Hypercholesterolemia; Hyperlipidemia
• Intervention / Treatment: Drug: PPD10558; Drug: Atorvastatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Furiex research site
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Furiex research site
    • Phoenix, Arizona, United States, 85023
      • Furiex research site
  • California
    • Huntington Park, California, United States, 90255
      • Furiex research site
    • Long Beach, California, United States, 90806
      • Furiex research site
    • Pismo Beach, California, United States, 93449
      • Furiex research site
    • San Diego, California, United States, 92103
      • Furiex research site
    • West Lake Village, California, United States, 91361
      • Furiex research site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Furiex research site
    • Golden, Colorado, United States, 80401
      • Furiex research site
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Furiex research site
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Furiex research site
    • Coral Gables, Florida, United States, 33134
      • Furiex research site
    • Deerfield Beach, Florida, United States, 33441
      • Furiex research site
    • Fort Lauderdale, Florida, United States, 33308
      • Furiex research site
    • Gainesville, Florida, United States, 32605
      • Furiex research site
    • Opa Locka, Florida, United States, 33054
      • Furiex research site
    • Pembroke, Florida, United States, 33024
      • Furiex research site
    • Pembroke, Florida, United States, 33028
      • Furiex research site
    • Sanford, Florida, United States, 32771
      • Furiex research site
    • West Palm Beach, Florida, United States, 33401
      • Furiex research site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Furiex research site
  • Idaho
    • Boise, Idaho, United States, 83704
      • Furiex research site
    • Nampa, Idaho, United States, 83686
      • Furiex research site
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Furiex research site
  • Kansas
    • Mission, Kansas, United States, 66202
      • Furiex research site
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Furiex research site
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Furiex research site
  • Maine
    • Auburn, Maine, United States, 04210
      • Furiex research site
  • Maryland
    • Oxon Hill, Maryland, United States, 20745
      • Furiex research site
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Furiex research site
  • Missouri
    • St. Louis, Missouri, United States, 63117
      • Furiex research site
  • Montana
    • Billings, Montana, United States, 59101
      • Furiex research site
    • Butte, Montana, United States, 59701
      • Furiex research site
    • Missoula, Montana, United States, 59808
      • Furiex research site
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Furiex research site
  • New York
    • Great Neck, New York, United States, 11023
      • Furiex research site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Furiex research site
    • Cary, North Carolina, United States, 27518
      • Furiex research site
    • Charlotte, North Carolina, United States, 28209
      • Furiex research site
    • Harrisburg, North Carolina, United States, 28075
      • Furiex research site
    • Hickory, North Carolina, United States, 28602
      • Furiex research site
    • Hickory, North Carolina, United States, 28601
      • Furiex research site
    • High Point, North Carolina, United States, 27262
      • Furiex research site
    • Raleigh, North Carolina, United States, 27609
      • Furiex research site
    • Raleigh, North Carolina, United States, 27612
      • Furiex research site
    • Wilmington, North Carolina, United States, 28401
      • Furiex research site
  • Ohio
    • Carlisle, Ohio, United States, 45005
      • Furiex research site
    • Cincinnati, Ohio, United States, 45236
      • Furiex research site
    • Columbus, Ohio, United States, 43213
      • Furiex research site
    • Kettering, Ohio, United States, 45429
      • Furiex research site
    • Springfield, Ohio, United States, 45505
      • Furiex research site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Furiex research site
    • Johnstown, Pennsylvania, United States, 15905
      • Furiex research site
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Furiex research site
    • East Providence, Rhode Island, United States, 02914
      • Furiex research site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Furiex research site
    • Greenville, South Carolina, United States, 29605
      • Furiex research site
    • Greer, South Carolina, United States, 29651
      • Furiex research site
    • Mt. Pleasant, South Carolina, United States, 29464
      • Furiex research site
    • Pawley's Island, South Carolina, United States, 29585
      • Furiex research site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Furiex research site
  • Texas
    • Tomball, Texas, United States, 77375
      • Furiex research site
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Furiex research site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Furiex research site
    • Richmond, Virginia, United States, 23294
      • Furiex research site
  • Washington
    • Spokane, Washington, United States, 99208
      • Furiex

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	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
Active Comparator: Atorvastatin; Dosing will be forced titrated as 40 mg orally once daily for 4 weeks, and 80 mg orally once daily for 8 weeks	Drug: 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 Comparator: Placebo; Dosing will be 2 placebo capsules twice daily for 12 weeks	Drug: Placebo; 2 placebo capsules twice daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Furiex Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (Estimate): January 19, 2011

Study Record Updates

• Last Update Posted (Estimate): December 22, 2011
• Last Update Submitted That Met QC Criteria: December 19, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Dyslipidemia; Hyperlipidemia; Metabolic diseases; Lipid metabolism disorders; Hyperlipoproteinemia Type IIa; Hyperlipoproteinemia Type IIb; Hypercholesterolemia, Autosomal Dominant; Hypercholesterolemia, Autosomal Dominant, Type B; Frederickson Type IIa; Frederickson Type IIb Hyperlipidemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Lipid Metabolism Disorders; Dyslipidemias; Myalgia; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: PPD10558-010