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