Efficacy and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients.
Ezetimibe added to statin therapy further reduces LDL-C and clinical atherosclerotic cardiovascular disease compared to statin alone. However, the number of effective and safe oral agents for patients not at LDL-C goal is limited. In prior clinical trials, gemcabene reduced LDL-C and was generally well-tolerated in nearly 900 patients treated for up to 12 weeks.



To evaluate the LDL-C lowering and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients.



This was an 8-week, double-blind, placebo-controlled, randomized, phase 2 study in men and postmenopausal women ≥18 and ≤65 years of age with LDL-C ≥130 mg/dL (3.4 mmol/L) while on low-intensity to high-intensity stable statin (the majority on moderate intensity) therapy. Sixty-six patients were randomized 1:1:1 to gemcabene 300 mg, 900 mg, or placebo QD.



Gemcabene 300 mg and 900 mg produced a mean percent change in LDL-C of -23.4 ± 4.7% (P = .005) and -27.7 ± 4.3% (P < .001), respectively, vs -6.2 ± 4.3% for placebo. The median percent change in CRP was -26.1% (P = .196) and -53.9% (P < .001) for gemcabene 300 mg and 900 mg, respectively, vs -11.1% for placebo. Gemcabene 300 mg and 900 mg were well-tolerated with no significant difference in AEs compared to placebo.



Gemcabene as add-on to stable statin therapy demonstrated additional dose-dependent and statistically significant reductions in LDL-C of >20% and CRP >40% compared to placebo. The results support gemcabene-continued development for patients requiring LDL-C lowering beyond that provided by background statin therapy.
Metabolic & Atherosclerosis Research Center, Cincinnati, OH.
Evan
E
Stein
Louisville Metabolic & Atherosclerotic Research Center, Louisville, KY.
Harold
H
Bays
Jacksonville Center for Clinical Research, Jacksonville, FL.
Michael
M
Koren
Gemphire Therapeutics Inc., Northville, MI.
Rebecca
R
Bakker-Arkema
Gemphire Therapeutics Inc., Northville, MI. Electronic address: cbisgaier@gemphire.com.
Charles
C
Bisgaier
D015746:Abdominal Pain / Q000209:etiology; D000293:Adolescent; D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D001247:Asthenia / Q000209:etiology; D001806:Blood Urea Nitrogen; D002097:C-Reactive Protein / Q000032:analysis; D002208:Caproates / Q000009:adverse effects / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D016896:Treatment Outcome; D055815:Young Adult
D001055:Apolipoproteins B; D002208:Caproates; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; C111024:gemcabene
Apolipoprotein B; C-reactive protein; Cardiovascular disease; Low-density lipoprotein cholesterol; Nonhigh-density lipoprotein cholesterol; Statins; Triglycerides; Very low-density lipoprotein