Clinical trial NCT02591836: Efficacy and Safety of Gemcabene in Hypercholesterolemic Patients as Monotherapy or in Combination With Atorvastatin
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: LDL-C
Lipid Regulator
Lead sponsor: NeuroBo Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


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 \<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

Primary outcomes:
measure: LDL-C percent change from baseline
timeFrame: 56 days
Secondary outcomes:
measure: HDL-C percent change from baseline
timeFrame: 56 days
measure: TG percent change from baseline
timeFrame: 56 days
measure: Apolipoprotein-B percent change from baseline
timeFrame: 56 days
measure: Adverse Events
timeFrame: 56 days
measure: Clinical Laboratory
timeFrame: 56 days
Other outcomes:
Locations:
Study officials:
References: