Author + information
- Diane MacDougall,
- James Vanderlugt,
- Noah Rosenberg,
- Lorenzo DiCarlo,
- Mark Milad,
- Janice Margulies and
- Roger Newton
ETC-1002, a novel oral drug that regulates imbalances in lipid and carbohydrate metabolism, is being developed to treat hypercholesterolemia and other cardio-metabolic risk factors.
Multiple ascending doses of ETC-1002 were evaluated in 56 healthy subjects, some with mildly elevated low density lipoprotein-cholesterol (LDL-C; >100 mg/dL), in two Phase 1, randomized, double-blind (sponsor open), placebo (PBO)-controlled studies. Seven cohorts of 8 subjects (6 active, 2 PBO) were treated for 14 days in the clinic with doses of 20 to 220 mg/day of ETC-1002 or PBO.
All subjects (93% male, mean age 36 years) with baseline LDL-C levels (mean/group) ranging from 100 to 138 mg/dL completed treatment. No clinically meaningful trends were identified in adverse events, clinical labs, vital signs or electrocardiograms related to treatment. ETC-1002 consistently lowered LDL-C in a dose related manner up to 36% (p<0.001) at the highest dose. The pharmacokinetics of ETC-1002 and its active metabolite showed increases in maximum concentration and area under the curve (AUC0-24 hour) with increasing dose; mean half-life values ranged from 16-33 hours.
ETC-1002 in a daily dose of up to 220 mg for 14 days was safe, well-tolerated and significantly reduced LDL-C in Phase 1 studies; pharmacokinetics support once daily dosing. These results provide a wide dosing range for Phase 2 testing in different populations with cardio-metabolic risk factors.
|Treatment||N||Least Squares Mean (SE)||Difference from PBO||p-value*|
|20 mg||6||3.5 (5.0)||−7.1||0.298|
|60 mg||6||−11.2 (5.1)||−21.8||0.004|
|100 mg||6||−16.5 (5.1)||−27.1||<0.001|
|120 mg||6||−15.0 (5.0)||−25.6||<0.001|
|140 mg||6||−21.3 (5.4)||−25.7||0.001|
|180 mg||6||−27.1 (5.4)||−31.5||<0.001|
|220 mg||6||−36.1 (5.4)||−40.5||<0.001|
↵* versus PBO using a mixed model repeat measures analysis
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Prevention: Treatment of Hyperlipidemia
Abstract Category: 24. Prevention: Clinical
Presentation Number: 1275-14
- 2013 American College of Cardiology Foundation