D D Kim1, J Krishnarajah2, S Lillioja3, F de Looze4,5, J Marjason6, J Proietto7, S Shakib8, B G A Stuckey9,10,11, J E Vath1, T E Hughes1. 1. Zafgen, Inc., Cambridge, MA, USA. 2. Linear Clinical Research Ltd, Nedlands, WA, Australia. 3. Clinical Informatics and CRTU-IHMRI, University of Wollongong, Wollongong, NSW, Australia. 4. AusTrials Pty Ltd, Sherwood, QLD, Australia. 5. School of Medicine, University of Queensland, Brisbane, QLD, Australia. 6. Q-Pharm, Herston, QLD, Australia. 7. Austin Health, Heidelberg, VIC, Australia. 8. CMAX Drug Studies Unit, Adelaide, SA, Australia. 9. Keogh Institute for Medical Research, Nedlands, WA, Australia. 10. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 11. School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.
Abstract
AIM: 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.
RCT Entities:
AIM: 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.
Authors: Shawn E McCandless; Jack A Yanovski; Jennifer Miller; Cary Fu; Lynne M Bird; Parisa Salehi; Christine L Chan; Diane Stafford; M Jennifer Abuzzahab; David Viskochil; Sarah E Barlow; Moris Angulo; Susan E Myers; Barbara Y Whitman; Dennis Styne; Elizabeth Roof; Elisabeth M Dykens; Ann O Scheimann; Jaret Malloy; Dongliang Zhuang; Kristin Taylor; Thomas E Hughes; Dennis D Kim; Merlin G Butler Journal: Diabetes Obes Metab Date: 2017-07-13 Impact factor: 6.577
Authors: Joseph Proietto; Jaret Malloy; Dongliang Zhuang; Mark Arya; Neale D Cohen; Ferdinandus J de Looze; Christopher Gilfillan; Paul Griffin; Stephen Hall; Thomas Nathow; Geoffrey S Oldfield; David N O'Neal; Adam Roberts; Bronwyn G A Stuckey; Dennis Yue; Kristin Taylor; Dennis Kim Journal: Diabetologia Date: 2018-07-11 Impact factor: 10.122