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

Phase 2

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Placebo; Drug: Gemcabene; Drug: Atorvastatin

• Registration Number: NCT02591836
• Lead Sponsor: NeuroBo Pharmaceuticals Inc.

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-01
• Primary Completion: 2003-06
• Study Completion: 2003-06
• Study First Submitted: 2015-10-22
• Study First Submitted QC: 2015-10-28
• Study First Posted: 2015-10-30
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-08
• Last Update Posted: 2020-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 277

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Gemcabene 300 mg & Atorvastatin 10 mg	Atorvastatin	-
Gemcabene 300 mg & Atorvastatin 80 mg	Gemcabene	-
Gemcabene 300 mg & Atorvastatin 80 mg	Atorvastatin	-
Gemcabene 600 mg & Atorvastatin 10 mg	Gemcabene	-
Gemcabene 600 mg & Atorvastatin 10 mg	Atorvastatin	-
Gemcabene 600 mg & Atorvastatin 80 mg	Gemcabene	-
Gemcabene 600 mg & Atorvastatin 80 mg	Atorvastatin	-
Gemcabene 900 mg & Atorvastatin 10 mg	Gemcabene	-
Gemcabene 900 mg & Atorvastatin 10 mg	Atorvastatin	-
Gemcabene 900 mg & Atorvastatin 40 mg	Gemcabene	-
Gemcabene 900 mg & Atorvastatin 80 mg	Atorvastatin	-
Gemcabene 900 mg & Atorvastatin 80 mg	Gemcabene	-
Atorvastatin 40 mg	Atorvastatin	-
Gemcabene 300 mg & Atorvastatin 10 mg	Gemcabene	-
Atorvastatin 10 mg	Atorvastatin	-
Atorvastatin 80 mg	Atorvastatin	-
Gemcabene 300 mg & Atorvastatin 40 mg	Gemcabene	-
Gemcabene 300 mg & Atorvastatin 40 mg	Atorvastatin	-
Gemcabene 600 mg & Atorvastatin 40 mg	Gemcabene	-
Gemcabene 600 mg & Atorvastatin 40 mg	Atorvastatin	-
Gemcabene 900 mg & Atorvastatin 40 mg	Atorvastatin	-
Gemcabene 300 mg	Gemcabene	Gemcabene 300 mg QD
Gemcabene 600 mg	Gemcabene	Gemcabene 600 mg QD
Gemcabene 900 mg	Gemcabene	Gemcabene 900 mg QD

Primary Outcome Measures

Name	Time	Method
LDL-C percent change from baseline	56 days

Secondary Outcome Measures

Name	Time	Method
Apolipoprotein-B percent change from baseline	56 days
Adverse Events	56 days
Clinical Laboratory	56 days	Clinical Laboratory Abnormalities
HDL-C percent change from baseline	56 days
TG percent change from baseline	56 days