Safety and Efficacy of an Extended-Release Peptide YY Analogue for Obesity: a Randomised, Placebo-Controlled, Phase 1 Trial.

AIMS Gut hormones such as peptide YY (PYY) activate satiety pathways and reduce body weight. We report the results from a Phase 1 trial of an extended-release PYY analogue, Y14, developed for treatment of obesity. METHODS Y14 was evaluated in overweight/obese volunteers in a Phase 1 randomised placebo-controlled trial, conducted in a clinical trial unit in the UK. Part A was a blinded single ascending dose study evaluating doses up to 36 mg. Part B was double-blinded and tested multiple ascending doses between 9 to 36 mg, given at 7-14 day intervals, over the course of 28 days with up to 5 doses given per subject. The primary outcome was safety and tolerability; the secondary outcome was to assess pharmacokinetics. Exploratory outcomes included food intake, body weight change and glucose tolerance after multiple doses. [ClinicalTrials.gov NCT03673111, EudraCT 2017-000380-33] RESULTS: Between Apr 11, 2017, and Dec 24, 2018 53 participants were enrolled into Part A and 24 into Part B. The pharmacokinetic characteristics were compatible with administration every 7-14 days. The most common adverse events (AE) were nausea, vomiting or administration site reactions which were mild in most cases and settled with time. No serious AE occurred. Subjects given multiple doses of Y14 lost between -2.87 to -3.58 kg body weight over placebo (p<0.0001) at 31 days from the first dose, with profound reductions in food intake of 38-55% (p<0.0001, compared to placebo) and there was no evidence of tachyphylaxis. CONCLUSIONS Our results support the continued development of Y14 as a novel treatment for obesity. This article is protected by copyright. All rights reserved.