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

January 18, 2011
December 19, 2011
March 2011
November 2011   (final data collection date for primary outcome measure)
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.
Incidence of stopping treatment with double-blinded study drug. [ Time Frame: Up to week 12 ] [ Designated as safety issue: No ]
As successful study treatment requires a patient to stay on the study through the End-of-study Visit, patients who withdraw from participating in the study prior to Week 12 will be considered to have stopped treatment with double-blinded study drug.
Complete list of historical versions of study NCT01279590 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change from Baseline in fasting lipid profile components (LDL-C, HDL-C, TG, TC, 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 (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 (TNF-α, CRP, and Lp-PLA2) [ Time Frame: Up to week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in patients' functional health and well-being as measured by the 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 ]
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Myalgia
  • Hypercholesterolemia
  • Hyperlipidemia
  • 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

  • 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

  • Drug: Placebo
    2 placebo capsules twice daily for 12 weeks
  • 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
    Intervention: Drug: PPD10558
  • 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
    Intervention: Drug: Atorvastatin
  • Placebo Comparator: Placebo
    Dosing will be 2 placebo capsules twice daily for 12 weeks
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
282
November 2011
November 2011   (final data collection date for primary outcome measure)

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.
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01279590
PPD10558-010
No
Furiex Pharmaceuticals, Inc
Furiex Pharmaceuticals, Inc
Not Provided
Not Provided
Furiex Pharmaceuticals, Inc
December 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP