A clinical trial assessing the safety and efficacy of the CB1R inverse agonist taranabant in obese and overweight patients: low-dose study.
OBJECTIVE
To evaluate the weight loss efficacy, safety and tolerability of taranabant, a CB1R inverse agonist, in obese and overweight patients.


METHODS
Multicenter, double-blind, randomized, placebo-controlled study.


METHODS
Patients >or=18 years old, BMI 27-43 kg m(-2), were randomized to placebo (n=209) or taranabant 0.5 mg (n=207), 1 mg (n=208) or 2 mg given orally once daily (n=417) for 52 weeks.


METHODS
Key efficacy measurements included body weight (BW), waist circumference (WC), lipid endpoints and glycemic endpoints.


RESULTS
Based on a last observation carried forward analysis of the all-patients-treated population, mean change in BW for taranabant 0.5, 1, and 2 mg and placebo was -5.4, -5.3, -6.7 and -1.7 kg, respectively (P<0.001 for all doses vs placebo). The proportions of patients who lost at least 5 and 10% of their baseline BW at week 52 were significantly higher for all taranabant doses vs placebo (P<0.001 for all doses). Reductions in WC, percentage of body fat, and triglycerides were significant for taranabant 2 mg and in triglycerides for taranabant 1 mg vs placebo. There was no effect of taranabant vs placebo on other lipid or glucose-related endpoints. Incidences of adverse experiences classified in the gastrointestinal (diarrhea and nausea), nervous system (dizziness/dizziness postural), psychiatric-related (irritability and anger/aggression) and vascular (flushing/hot flush) organ systems were higher and statistically significant in the taranabant 2-mg group compared with the placebo group. Irritability was higher and statistically significant in all taranabant groups compared with the placebo group.


CONCLUSIONS
All three doses of taranabant-induced clinically meaningful and statistically significant weight loss. Incidences of adverse experiences in organ systems known to express CB1R were higher in taranabant groups.
Proietto
J
J
Department of Medicine, University of Melbourne, Heidelberg Repatriation Hospital, Melbourne, Victoria, Australia. j.proietto@unimelb.edu.au
Rissanen
A
A
Harp
J B
JB
Erondu
N
N
Yu
Q
Q
Suryawanshi
S
S
Jones
M E
ME
Johnson-Levonas
A O
AO
Heymsfield
S B
SB
Kaufman
K D
KD
Amatruda
J M
JM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000577:Amides / Q000008:administration & dosage*; D019440:Anti-Obesity Agents / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D011725:Pyridines / Q000008:administration & dosage*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D011795:Surveys and Questionnaires; D015431:Weight Loss; D055815:Young Adult
D000577:Amides; D019440:Anti-Obesity Agents; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; C521311:N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide