Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial.
OBJECTIVE
To assess the efficacy, safety and tolerability of beloranib treatment for obesity.


METHODS
This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4 mg) or placebo, administered subcutaneously, for 12 weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered.


RESULTS
At week 12, beloranib resulted in dose-dependent progressive weight loss of -5.5 ± 0.5, -6.9 ± 0.6 and -10.9 ± 1.1 kg for the 0.6, 1.2 and 2.4 mg beloranib doses, respectively, compared with -0.4 ± 0.4 kg with placebo (all p < 0.0001 vs placebo). Weight loss with beloranib was associated with corresponding reductions in waist circumference and body fat mass, as well as improvements in lipids, high-sensitivity C-reactive protein and blood pressure. Sleep disturbance and gastrointestinal adverse events were more common with beloranib than with placebo; these were generally mild to moderate, transient and dose-related, and led to more early study withdrawals in participants in the group with the highest dose of beloranib.


CONCLUSIONS
In this 12-week phase II study, beloranib produced clinically and statistically significant weight loss and corresponding improvements in cardiometabolic risk factors. Beloranib appeared safe, and the 0.6 and 1.2 mg doses were generally well tolerated. The 2.4 mg dose was associated with increased sleep latency and mild to moderate gastrointestinal adverse events over the first month of treatment. These findings represent a novel mechanism for producing clinically meaningful weight loss.
Zafgen, Inc., Cambridge, MA, USA.
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http://orcid.org/0000-0001-5333-5240
DD
Kim
Linear Clinical Research Ltd, Nedlands, WA, Australia.
J
J
Krishnarajah
Clinical Informatics and CRTU-IHMRI, University of Wollongong, Wollongong, NSW, Australia.
S
S
Lillioja
AusTrials Pty Ltd, Sherwood, QLD, Australia.|School of Medicine, University of Queensland, Brisbane, QLD, Australia.
F
F
de Looze
Q-Pharm, Herston, QLD, Australia.
J
J
Marjason
Austin Health, Heidelberg, VIC, Australia.
J
J
Proietto
CMAX Drug Studies Unit, Adelaide, SA, Australia.
S
S
Shakib
Keogh Institute for Medical Research, Nedlands, WA, Australia.|Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.|School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.
B G A
BGA
Stuckey
Zafgen, Inc., Cambridge, MA, USA.
J E
JE
Vath
Zafgen, Inc., Cambridge, MA, USA.
T E
TE
Hughes
D000293:Adolescent; D000328:Adult; D000368:Aged; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000187:drug effects; D002934:Cinnamates / Q000627:therapeutic use*; D003510:Cyclohexanes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D020920:Dyssomnias / Q000139:chemically induced; D004852:Epoxy Compounds / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D012307:Risk Factors; D012717:Sesquiterpenes / Q000627:therapeutic use*; D055105:Waist Circumference; D015431:Weight Loss / Q000187:drug effects*; D055815:Young Adult
D019440:Anti-Obesity Agents; D002934:Cinnamates; D003510:Cyclohexanes; D004852:Epoxy Compounds; D008055:Lipids; D012717:Sesquiterpenes; D002097:C-Reactive Protein; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases; C487952:CKD732
clinical trial; drug development; obesity therapy; randomized trial; weight loss therapy