Hypercholesterolemia
Conditions
Keywords
LDL-C, Lipid Regulator
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.
Interventions
Sponsors
NeuroBo Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| LDL-C percent change from baseline | 56 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 56 days | Clinical Laboratory Abnormalities |
Outcome results
None listed