Efficacy and Safety of Gemcabene in Hypercholesterolemic Patients as Monotherapy or in Combination With Atorvastatin
Efficacy and Safety of Gemcabene in Hypercholesterolemic Patients as Monotherapy or in Combination With Atorvastatin
The primary purpose of this placebo-controlled study is to evaluate the low-density
 lipoprotein cholesterol (LDL-C) efficacy and dose-response of gemcabene 300, 600 and 900
 mg/day administered as monotherapy or in combination with atorvastatin 10, 40, and 80 mg/day
 to hypercholesterolemic patients.

 Secondary purposes include evaluating the effects of high-sensitivity C-reactive protein
 (hsCRP), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and apolipoprotein
 B (ApoB), and safety and efficacy of gemcabene monotherapy and gemcabene/atorvastatin
 combination.
Inclusion Criteria:

 -  Males and Females

 -  18-70 years old

 -  Received a statin as monotherapy while having a LDL-C >100 mg d/L at initial clinical
 washout visit OR

 -  Received no lipid-altering drugs since the initial clinic washout visit and had a mean
 LDL-C as follows at 2 qualifying visits:

 -  ≥ 130 mg/dL if National Cholesterol Education Program (NCEP) Adult Treatment Panel III
 (ATP III) Coronary Heard Disease (CHD) risk ≥ 10%; OR

 -  ≥ 160 mg/dL if NCEP ATP III CHD risk < 10%

 -  Had variability of 2 qualifying LDL-C <20% (i.e. lowest value/highest value >0.8). An
 additional qualifying visit may have been completed by patients who were washing off
 lipid medication in order to reassess LDL-C variability; and

 -  Had a mean LDL-C < 250 mg/dL at 2 qualifying visits

 Exclusion Criteria:

 -  Women of childbearing potential, pregnant or lactating;

 -  Body Mass Index (BMI) >38kg/m²;

 -  TG >400 mg/dL at Visit B2 or B3

 -  Unexplained creatinine phosphokinase (CPK) > 3 x Upper Limit of Normal (ULN) or those
 with a history of unexplained myopathy (including rhabdomyolysis);

 -  Documented cardiac history of: Myocardial infarction*, severe or unstable angina
 pectoris, coronary angioplasty, coronary artery bypass graft, symptomatic carotid
 artery disease or peripheral artery disease, ventricular arrhythmias, recurrent
 supraventricular tachycardia, abnormal QTC interval (QT corrected > 0.44 sec), heart
 failure or any other major cardiovascular event resulting in hospitalization

 -  Uncontrolled hypertension*

 -  Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (HbA1c >8%) or any
 diabetic patient who takes insulin and/or thiazolidinediones

 -  Renal dysfunction including chronic renal failure or insufficiency, or creatinine >2.0
 mg/dL;

 -  Hepatic dysfunction

 -  Uncontrolled hypothyroidism

 -  Abnormal urinalysis

 -  Currently taking any of the following medications:

 -  Potent CYP3A4 inhibitors including indinavir, nelfinavir, ritonavir, saquinavir,
 amiodarone, cimetidine, clarithromycin, erythromycin, erythromycin, fluoxetine,
 itraconazole, ketoconazole, nefazodone and troleandomycin as well as grapefruit juice;

 -  Thiazolidinediones (Avandia, Actos);

 -  Immunosuppressive agents;

 -  St. John's wort

 -  Taking any of the following lipid-altering medications within 5 weeks prior to
 randomization:

 -  Lipid-regulating drugs: Niacin (crystalline >500mg/day, slow release or time release),
 psyllium preparation such as Metamucil (>2 tablespoons/day), fibrates and derivatives,
 bile cholesterol absorption inhibitors including ezetimibe;

 -  Any supplement containing plan sterols/stanols (i.e. Benecol, beta-sitosterol,
 Cholestatin, Phytoquest, Take Control) or cholestin (i.e. Chinese red yeast, fermented
 on rice; Hong Qu, Hong Chu, Herbvalin, Ruby Monascus, Monascus purpureus rice);

 -  Neomycin (oral);

 -  Adrenocortical steroids*

 -  Sibutramine (Meridia);

 -  Insulin;

 -  Orlistat (Xenical);

 -  Isotretinoin