efficacy and safety of gemcabene in hypercholesterolemic patients as monotherapy or in combination with atorvastatin

Conditions: Hypercholesterolemia

Summary: 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.


Eligibility criteria:
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 \ 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

Keywords: ldl-c lipid regulator