Pharmacokinetics, safety, and tolerability of phentermine in healthy participants receiving taranabant, a novel cannabinoid-1 receptor (CB1R) inverse agonist.
This study assessed the potential pharmacokinetic interaction and safety/tolerability of taranabant and phentermine coadministration. This was a randomized, double-blind, 3-panel, fixed-sequence study in healthy participants. Panels A, B, and C evaluated the safety/tolerability of phentermine 15 mg coadministered with taranabant 0.5, 1, and 2 mg for 7 days (panel A) and 28 days (panels B and C). In panels A and C, phentermine 15 mg was administered both with (7 days, panel A; 28 days, panel C) and without (7 days) taranabant 0.5 mg or 2 mg to evaluate pharmacokinetics. The primary endpoint was phentermine AUC(0-24 h) in panels A and C. Secondary endpoints were changes from baseline in blood pressure and heart rate for all panels. The geometric mean ratios and 90% confidence intervals for phentermine AUC(0-24 h) in the presence/absence of taranabant 0.5 mg and 2 mg were 1.08 (0.99, 1.17) and 1.04 (0.98, 1.10), respectively. No significant differences in blood pressure and heart rate were observed with any treatment versus placebo. Coadministration of taranabant 0.5 mg, 1 mg, and 2 mg with phentermine was well tolerated with no pharmacokinetic interaction and did not result in meaningful changes in blood pressure or heart rate versus placebo.
Addy
Carol
C
Merck Research Laboratories, Boston, MA 02115, USA. carol_addy@merck.com
Jumes
Patricia
P
Rosko
Kimberly
K
Li
Susie
S
Li
Hankun
H
Maes
Andrea
A
Johnson-Levonas
Amy O
AO
Chodakewitz
Jeffrey
J
Stoch
S Aubrey
SA
Wagner
John A
JA
D000293:Adolescent; D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects*; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D004347:Drug Interactions; D054314:Drug Inverse Agonism; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010645:Phentermine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*
D000577:Amides; D019440:Anti-Obesity Agents; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D010645:Phentermine; C521311:N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide