Efficacy and safety of ETC-1002, a novel investigational low-density
lipoprotein-cholesterol-lowering therapy for the treatment of patients with
hypercholesterolemia and type 2 diabetes mellitus.
Author(s): Gutierrez MJ(1), Rosenberg NL, Macdougall DE, Hanselman JC, Margulies JR, Strange
P, Milad MA, McBride SJ, Newton RS.
Affiliation(s): Author information:
(1)From Comprehensive Clinical Development, Miramar, FL (M.J.G.); Esperion
Therapeutics Inc, Plymouth, MI (N.L.R., D.E.M., J.C.H., J.R.M., R.S.N.);
Integrated Medical Development LLC, Princeton Junction, NJ (P.S.); Milad
Consulting, Plymouth, MI (M.A.M.); and United BioSource Corporation, Ann Arbor,
MI (S.J.M.).
Publication date & source: 2014, Arterioscler Thromb Vasc Biol. , 34(3):676-83
OBJECTIVE: 8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (ETC-1002) is a
small molecule with a unique mechanism of action shown in nonclinical studies to
modulate pathways of cholesterol, fatty acid, and carbohydrate metabolism. In
previous phase 2 clinical trials, once daily oral treatment with ETC-1002
significantly reduced low-density lipoprotein-cholesterol in patients with
hypercholesterolemia. In this trial, the lipid-lowering efficacy of ETC-1002 was
evaluated in patients with type 2 diabetes mellitus and hypercholesterolemia.
Additional cardiometabolic biomarkers, including glycemic measures, were also
assessed.
APPROACH AND RESULTS: A single-center, double-blind, placebo-controlled trial
evaluated 60 patients with type 2 diabetes mellitus and elevated low-density
lipoprotein-cholesterol. Patients discontinued all diabetes mellitus and
lipid-regulating drugs and were randomized to receive ETC-1002 80 mg QD for 2
weeks followed by 120 mg QD for 2 weeks or placebo for 4 weeks. ETC-1002 lowered
low-density lipoprotein-cholesterol levels by 43±2.6% (least squares mean±SE),
compared with a reduction of 4±2.5% by placebo at day 29 (P<0.0001; primary end
point). Non-high-density lipoprotein-cholesterol and total cholesterol were also
significantly lowered by ETC-1002 compared with placebo (P<0.0001).
High-sensitivity C-reactive protein was reduced by 41% (median) compared with a
placebo reduction of 11% (P=0.0011). No clinically meaningful safety findings
were observed.
CONCLUSIONS: ETC-1002 lowered low-density lipoprotein-cholesterol and other
lipids and demonstrated improvement in high-sensitivity C-reactive protein in
patients with type 2 diabetes mellitus and hypercholesterolemia without worsening
glycemic control. ETC-1002 was well tolerated in this population.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
identifier: NCT# 01607294.
|