Efficacy and Safety of Gemcabene in Hypercholesterolemic Patients as Monotherapy or in Combination With Atorvastatin

Study Overview
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Brief Summary
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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.

Official Title
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An 8-Week, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of Gemcabene Administered as Monotherapy or in Combination With Atorvastatin in the Treatment of Hypercholesterolemic Patients

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: Gemcabene
* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcabene 300 mg<br>Gemcabene 300 mg QD | Drug: Gemcabene<br>* Gemcabene<br>|
| Experimental: Gemcabene 600 mg<br>Gemcabene 600 mg QD | Drug: Gemcabene<br>* Gemcabene<br>|
| Experimental: Gemcabene 900 mg<br>Gemcabene 900 mg QD | Drug: Gemcabene<br>* Gemcabene<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Active Comparator: Atorvastatin 10 mg<br> | Drug: Atorvastatin<br>* Atorvastatin<br>|
| Active Comparator: Atorvastatin 40 mg<br> | Drug: Atorvastatin<br>* Atorvastatin<br>|
| Active Comparator: Atorvastatin 80 mg<br> | Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 300 mg & Atorvastatin 10 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 300 mg & Atorvastatin 40 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 300 mg & Atorvastatin 80 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 600 mg & Atorvastatin 10 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 600 mg & Atorvastatin 40 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 600 mg & Atorvastatin 80 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 900 mg & Atorvastatin 10 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 900 mg & Atorvastatin 40 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|
| Experimental: Gemcabene 900 mg & Atorvastatin 80 mg<br> | Drug: Gemcabene<br>* Gemcabene<br>Drug: Atorvastatin<br>* Atorvastatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C percent change from baseline |  | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDL-C percent change from baseline |  | 56 days | 
| TG percent change from baseline |  | 56 days | 
| Apolipoprotein-B percent change from baseline |  | 56 days | 
| Adverse Events |  | 56 days | 
| Clinical Laboratory | Clinical Laboratory Abnormalities | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL-C, Lipid Regulator