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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Furiex Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01279590
First received: January 18, 2011
Last updated: December 19, 2011
Last verified: December 2011
  Purpose

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 Intervention Phase
Myalgia
Hypercholesterolemia
Hyperlipidemia
Drug: PPD10558
Drug: Atorvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Furiex Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia. [ Time Frame: Up to week 12 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Frequency of pain rescue medication [ Time Frame: Up to week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to onset of statin -associated myalgia (SAM) [ Time Frame: Up to week 12 ] [ Designated as safety issue: No ]
  • Time to stopping treatment with study drug due to SAM [ Time Frame: Up to week 12 ] [ Designated as safety issue: No ]

Enrollment: 282
Study Start Date: March 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01279590

  Show 67 Study Locations
Sponsors and Collaborators
Furiex Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Furiex Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01279590     History of Changes
Other Study ID Numbers: PPD10558-010
Study First Received: January 18, 2011
Last Updated: December 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Furiex Pharmaceuticals, Inc:
Hyperlipidemia
Dyslipidemia
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:
Hyperlipidemias
Hypercholesterolemia
Myalgia
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Muscular Diseases
Musculoskeletal Diseases
Musculoskeletal Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Neuromuscular Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014