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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01279590
Recruitment Status : Completed
First Posted : January 19, 2011
Last Update Posted : December 22, 2011
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Myalgia Hypercholesterolemia Hyperlipidemia Drug: PPD10558 Drug: Atorvastatin Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 282 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : March 2011
Actual Primary Completion Date : November 2011
Actual Study Completion Date : November 2011

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

Primary Outcome Measures :
  1. Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia. [ Time Frame: 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 :
  1. 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) [ Time Frame: Up to week 12 ]
  2. Change from baseline in muscle strength measurements (Sit-to-stand(STS) performance and hand grip strength by Jamar Hydraulic Hand Dynamometer) [ Time Frame: Up to week 12 ]
  3. Frequency of pain rescue medication [ Time Frame: Up to week 12 ]
  4. Change from Baseline in inflammatory markers (Tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2)) [ Time Frame: Up to week 12 ]
  5. Change in patients' functional health and well-being as measured by the Short Form-36v2 Health Survey (SF-36) [ Time Frame: Up to week 12 ]
  6. Time to onset of statin -associated myalgia (SAM) [ Time Frame: Up to week 12 ]
  7. Time to stopping treatment with study drug due to SAM [ Time Frame: Up to week 12 ]

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Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01279590

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United States, Alabama
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Anniston, Alabama, United States, 36207
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Phoenix, Arizona, United States, 85018
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Phoenix, Arizona, United States, 85023
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Huntington Park, California, United States, 90255
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Long Beach, California, United States, 90806
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San Diego, California, United States, 92103
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West Lake Village, California, United States, 91361
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Colorado Springs, Colorado, United States, 80907
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Golden, Colorado, United States, 80401
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Hartford, Connecticut, United States, 06102
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Boynton Beach, Florida, United States, 33472
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Coral Gables, Florida, United States, 33134
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Deerfield Beach, Florida, United States, 33441
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Fort Lauderdale, Florida, United States, 33308
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Gainesville, Florida, United States, 32605
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Great Neck, New York, United States, 11023
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Asheville, North Carolina, United States, 28803
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Cary, North Carolina, United States, 27518
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Charlotte, North Carolina, United States, 28209
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Harrisburg, North Carolina, United States, 28075
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Hickory, North Carolina, United States, 28601
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Hickory, North Carolina, United States, 28602
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Salt Lake City, Utah, United States, 84124
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Spokane, Washington, United States, 99208
Sponsors and Collaborators
Furiex Pharmaceuticals, Inc

Responsible Party: Furiex Pharmaceuticals, Inc Identifier: NCT01279590     History of Changes
Other Study ID Numbers: PPD10558-010
First Posted: January 19, 2011    Key Record Dates
Last Update Posted: December 22, 2011
Last Verified: December 2011

Keywords provided by Furiex Pharmaceuticals, Inc:
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:
Lipid Metabolism Disorders
Metabolic Diseases
Muscular Diseases
Musculoskeletal Diseases
Musculoskeletal Pain
Neurologic Manifestations
Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors