Clinical trial NCT01279590: Study of the Safety and Tolerability Associated With PPD10558 Versus Atorvastatin in Patients Previously Intolerant to Statins Due to Statin-associated Myalgia (SAM)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Furiex Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2011-01-19
Enrollment: 282
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of stopping treatment with double-blinded study drug due to statin-associated myalgia.
timeFrame: Up to week 12
Secondary outcomes:
measure: 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)
timeFrame: Up to week 12
measure: Change from baseline in muscle strength measurements (Sit-to-stand(STS) performance and hand grip strength by Jamar Hydraulic Hand Dynamometer)
timeFrame: Up to week 12
measure: Frequency of pain rescue medication
timeFrame: Up to week 12
measure: Change from Baseline in inflammatory markers (Tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2))
timeFrame: Up to week 12
measure: Change in patients' functional health and well-being as measured by the Short Form-36v2 Health Survey (SF-36)
timeFrame: Up to week 12
measure: Time to onset of statin -associated myalgia (SAM)
timeFrame: Up to week 12
measure: Time to stopping treatment with study drug due to SAM
timeFrame: Up to week 12
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Furiex research site
state: Alabama
city: Phoenix
country: United States
facility: Furiex research site
state: Arizona
city: Phoenix
country: United States
facility: Furiex research site
state: Arizona
city: Huntington Park
country: United States
facility: Furiex research site
state: California
city: Long Beach
country: United States
facility: Furiex research site
state: California
city: Pismo Beach
country: United States
facility: Furiex research site
state: California
city: San Diego
country: United States
facility: Furiex research site
state: California
city: West Lake Village
country: United States
facility: Furiex research site
state: California
city: Colorado Springs
country: United States
facility: Furiex research site
state: Colorado
city: Golden
country: United States
facility: Furiex research site
state: Colorado
city: Hartford
country: United States
facility: Furiex research site
state: Connecticut
city: Boynton Beach
country: United States
facility: Furiex research site
state: Florida
city: Coral Gables
country: United States
facility: Furiex research site
state: Florida
city: Deerfield Beach
country: United States
facility: Furiex research site
state: Florida
city: Fort Lauderdale
country: United States
facility: Furiex research site
state: Florida
city: Gainesville
country: United States
facility: Furiex research site
state: Florida
city: Opa Locka
country: United States
facility: Furiex research site
state: Florida
city: Pembroke
country: United States
facility: Furiex research site
state: Florida
city: Pembroke
country: United States
facility: Furiex research site
state: Florida
city: Sanford
country: United States
facility: Furiex research site
state: Florida
city: West Palm Beach
country: United States
facility: Furiex research site
state: Florida
city: Honolulu
country: United States
facility: Furiex research site
state: Hawaii
city: Boise
country: United States
facility: Furiex Research site
state: Idaho
city: Nampa
country: United States
facility: Furiex research site
state: Idaho
city: Chicago
country: United States
facility: Furiex research site
state: Illinois
city: Mission
country: United States
facility: Furiex research site
state: Kansas
city: Madisonville
country: United States
facility: Furiex research site
state: Kentucky
city: Covington
country: United States
facility: Furiex research site
state: Louisiana
city: Auburn
country: United States
facility: Furiex research site
state: Maine
city: Oxon Hill
country: United States
facility: Furiex research site
state: Maryland
city: Bay City
country: United States
facility: Furiex research site
state: Michigan
city: St. Louis
country: United States
facility: Furiex research site
state: Missouri
city: Billings
country: United States
facility: Furiex research site
state: Montana
city: Butte
country: United States
facility: Furiex research site
state: Montana
city: Missoula
country: United States
facility: Furiex research site
state: Montana
city: Omaha
country: United States
facility: Furiex research site
state: Nebraska
city: Great Neck
country: United States
facility: Furiex research site
state: New York
city: Asheville
country: United States
facility: Furiex research site
state: North Carolina
city: Cary
country: United States
facility: Furiex research site
state: North Carolina
city: Charlotte
country: United States
facility: Furiex research site
state: North Carolina
city: Harrisburg
country: United States
facility: Furiex research site
state: North Carolina
city: Hickory
country: United States
facility: Furiex research site
state: North Carolina
city: Hickory
country: United States
facility: Furiex research site
state: North Carolina
city: High Point
country: United States
facility: Furiex research site
state: North Carolina
city: Raleigh
country: United States
facility: Furiex research site
state: North Carolina
city: Raleigh
country: United States
facility: Furiex research site
state: North Carolina
city: Wilmington
country: United States
facility: Furiex research site
state: North Carolina
city: Carlisle
country: United States
facility: Furiex research site
state: Ohio
city: Cincinnati
country: United States
facility: Furiex research site
state: Ohio
city: Columbus
country: United States
facility: Furiex research site
state: Ohio
city: Kettering
country: United States
facility: Furiex research site
state: Ohio
city: Springfield
country: United States
facility: Furiex research site
state: Ohio
city: Altoona
country: United States
facility: Furiex research site
state: Pennsylvania
city: Johnstown
country: United States
facility: Furiex research site
state: Pennsylvania
city: Cumberland
country: United States
facility: Furiex research site
state: Rhode Island
city: East Providence
country: United States
facility: Furiex research site
state: Rhode Island
city: Anderson
country: United States
facility: Furiex research site
state: South Carolina
city: Greenville
country: United States
facility: Furiex research site
state: South Carolina
city: Greer
country: United States
facility: Furiex research site
state: South Carolina
city: Mt. Pleasant
country: United States
facility: Furiex research site
state: South Carolina
city: Pawley's Island
country: United States
facility: Furiex research site
state: South Carolina
city: Bristol
country: United States
facility: Furiex research site
state: Tennessee
city: Tomball
country: United States
facility: Furiex research site
state: Texas
city: Salt Lake City
country: United States
facility: Furiex research site
state: Utah
city: Norfolk
country: United States
facility: Furiex research site
state: Virginia
city: Richmond
country: United States
facility: Furiex research site
state: Virginia
city: Spokane
country: United States
facility: Furiex
state: Washington
Study officials:
References: