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

NCT01279590 | Completed Phase 2

• 1 other identifier: PPD10558-010
• Study Type: interventional
• Target: 282
• Locations: 1 country
• Sites: 67

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.

Conditions

Myalgia; Hypercholesterolemia; Hyperlipidemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (3)

PPD10558

EXPERIMENTAL

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

Atorvastatin

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Dosing will be 2 placebo capsules twice daily for 12 weeks

Drug: Placebo

Interventions

PPD10558 DRUG

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

PPD10558

Atorvastatin DRUG

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

Atorvastatin

Placebo DRUG

2 placebo capsules twice daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Furiex Pharmaceuticals, Inc: lead

Study Sites (67)

Furiex research site

Anniston, Alabama, 36207, United States

Location

Furiex research site

Phoenix, Arizona, 85018, United States

Location

Furiex research site

Phoenix, Arizona, 85023, United States

Location

Furiex research site

Huntington Park, California, 90255, United States

Location

Furiex research site

Long Beach, California, 90806, United States

Location

Furiex research site

Pismo Beach, California, 93449, United States

Location

Furiex research site

San Diego, California, 92103, United States

Location

Furiex research site

West Lake Village, California, 91361, United States

Location

Furiex research site

Colorado Springs, Colorado, 80907, United States

Location

Furiex research site

Golden, Colorado, 80401, United States

Location

Furiex research site

Hartford, Connecticut, 06102, United States

Location

Furiex research site

Boynton Beach, Florida, 33472, United States

Location

Furiex research site

Coral Gables, Florida, 33134, United States

Location

Furiex research site

Deerfield Beach, Florida, 33441, United States

Location

Furiex research site

Fort Lauderdale, Florida, 33308, United States

Location

Furiex research site

Gainesville, Florida, 32605, United States

Location

Furiex research site

Opa-locka, Florida, 33054, United States

Location

Furiex research site

Pembroke, Florida, 33024, United States

Location

Furiex research site

Pembroke, Florida, 33028, United States

Location

Furiex research site

Sanford, Florida, 32771, United States

Location

Furiex research site

West Palm Beach, Florida, 33401, United States

Location

Furiex research site

Honolulu, Hawaii, 96814, United States

Location

Furiex Research site

Boise, Idaho, 83704, United States

Location

Furiex research site

Nampa, Idaho, 83686, United States

Location

Furiex research site

Chicago, Illinois, 60616, United States

Location

Furiex research site

Mission, Kansas, 66202, United States

Location

Furiex research site

Madisonville, Kentucky, 42431, United States

Location

Furiex research site

Covington, Louisiana, 70433, United States

Location

Furiex research site

Auburn, Maine, 04210, United States

Location

Furiex research site

Oxon Hill, Maryland, 20745, United States

Location

Furiex research site

Bay City, Michigan, 48706, United States

Location

Furiex research site

St Louis, Missouri, 63117, United States

Location

Furiex research site

Billings, Montana, 59101, United States

Location

Furiex research site

Butte, Montana, 59701, United States

Location

Furiex research site

Missoula, Montana, 59808, United States

Location

Furiex research site

Omaha, Nebraska, 68144, United States

Location

Furiex research site

Great Neck, New York, 11023, United States

Location

Furiex research site

Asheville, North Carolina, 28803, United States

Location

Furiex research site

Cary, North Carolina, 27518, United States

Location

Furiex research site

Charlotte, North Carolina, 28209, United States

Location

Furiex research site

Harrisburg, North Carolina, 28075, United States

Location

Furiex research site

Hickory, North Carolina, 28601, United States

Location

Furiex research site

Hickory, North Carolina, 28602, United States

Location

Furiex research site

High Point, North Carolina, 27262, United States

Location

Furiex research site

Raleigh, North Carolina, 27609, United States

Location

Furiex research site

Raleigh, North Carolina, 27612, United States

Location

Furiex research site

Wilmington, North Carolina, 28401, United States

Location

Furiex research site

Carlisle, Ohio, 45005, United States

Location

Furiex research site

Cincinnati, Ohio, 45236, United States

Location

Furiex research site

Columbus, Ohio, 43213, United States

Location

Furiex research site

Kettering, Ohio, 45429, United States

Location

Furiex research site

Springfield, Ohio, 45505, United States

Location

Furiex research site

Altoona, Pennsylvania, 16602, United States

Location

Furiex research site

Johnstown, Pennsylvania, 15905, United States

Location

Furiex research site

Cumberland, Rhode Island, 02864, United States

Location

Furiex research site

East Providence, Rhode Island, 02914, United States

Location

Furiex research site

Anderson, South Carolina, 29621, United States

Location

Furiex research site

Greenville, South Carolina, 29605, United States

Location

Furiex research site

Greer, South Carolina, 29651, United States

Location

Furiex research site

Mt. Pleasant, South Carolina, 29464, United States

Location

Furiex research site

Pawleys Island, South Carolina, 29585, United States

Location

Furiex research site

Bristol, Tennessee, 37620, United States

Location

Furiex research site

Tomball, Texas, 77375, United States

Location

Furiex research site

Salt Lake City, Utah, 84124, United States

Location

Furiex research site

Norfolk, Virginia, 23502, United States

Location

Furiex research site

Richmond, Virginia, 23294, United States

Location

Furiex

Spokane, Washington, 99208, United States

Location

MeSH Terms

Conditions

Myalgia; Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipoproteinemia Type II

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Musculoskeletal Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2011
• First Posted: January 19, 2011
• Study Start: March 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 22, 2011

Record last verified: 2011-12

Locations

US (67)