PMID- 33606914
OWN - NLM
STAT- MEDLINE
DCOM- 20210630
LR  - 20210630
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 23
IP  - 7
DP  - 2021 Jul
TI  - Safety and efficacy of an extended-release peptide YY analogue for obesity: A 
      randomized, placebo-controlled, phase 1 trial.
PG  - 1471-1483
LID - 10.1111/dom.14358 [doi]
AB  - AIM: To report the results from a Phase 1 trial of an extended-release peptide YY 
      analogue, Y14, developed for the treatment of obesity. METHODS: Y14 was evaluated 
      in overweight/obese volunteers in a Phase 1 randomized placebo-controlled trial, 
      conducted in a clinical trial unit in the United Kingdom. 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 and 36 mg, given at 
      7- to 14-day intervals, over the course of 28 days, with up to five doses given 
      per participant. The primary outcome was safety and tolerability; the secondary 
      outcome was assessment of pharmacokinetic (PK) characteristics. Exploratory 
      outcomes included food intake, body weight change and glucose tolerance after 
      multiple doses. RESULTS: Between April 11, 2017 and December 24, 2018, 53 
      participants were enrolled into Part A and 24 into Part B of the trial. The PK 
      characteristics were compatible with administration every 7 to 14 days. The most 
      common adverse events (AEs) were nausea, vomiting or administration site 
      reactions, which were mild in most cases and settled with time. No serious AE 
      occurred. Participants given multiple doses of Y14 lost between -2.87 and 
      -3.58 kg body weight compared with placebo (P <0.0001) at 31 days from the first 
      dose, with profound reductions in food intake of 38% to 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.
CI  - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Tan, Tricia M-M
AU  - Tan TM
AUID- ORCID: 0000-0001-5873-3432
AD  - Department of Metabolism, Digestion and Reproduction, Imperial College London, 
      London, UK.
AD  - Zihipp Ltd, London, UK.
FAU - Minnion, James
AU  - Minnion J
AD  - Department of Metabolism, Digestion and Reproduction, Imperial College London, 
      London, UK.
AD  - Zihipp Ltd, London, UK.
FAU - Khoo, Bernard
AU  - Khoo B
AD  - Division of Medicine, University College London, London, UK.
FAU - Ball, Laura-Jayne
AU  - Ball LJ
AD  - Department of Metabolism, Digestion and Reproduction, Imperial College London, 
      London, UK.
FAU - Malviya, Reshma
AU  - Malviya R
AD  - Department of Metabolism, Digestion and Reproduction, Imperial College London, 
      London, UK.
AD  - Zihipp Ltd, London, UK.
FAU - Day, Emily
AU  - Day E
AD  - Imperial Clinical Trials Unit, Imperial College London, London, UK.
FAU - Fiorentino, Francesca
AU  - Fiorentino F
AD  - Imperial Clinical Trials Unit, Imperial College London, London, UK.
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Brindley, Charlie
AU  - Brindley C
AD  - Kinetassist Ltd., Quothquan, UK.
FAU - Bush, Jim
AU  - Bush J
AD  - Covance Clinical Research Unit, Leeds, UK.
FAU - Bloom, Stephen R
AU  - Bloom SR
AD  - Department of Metabolism, Digestion and Reproduction, Imperial College London, 
      London, UK.
AD  - Zihipp Ltd, London, UK.
LA  - eng
GR  - G0802390/MRC_/Medical Research Council/United Kingdom
GR  - G1000474/MRC_/Medical Research Council/United Kingdom
GR  - MR/L013088/1/MRC_/Medical Research Council/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210309
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 106388-42-5 (Peptide YY)
SB  - IM
MH  - Double-Blind Method
MH  - Humans
MH  - *Obesity/drug therapy
MH  - Overweight
MH  - *Peptide YY
MH  - United Kingdom
OTO - NOTNLM
OT  - clinical trial
OT  - obesity
OT  - peptide YY
OT  - pharmacokinetics
OT  - safety
OT  - weight loss
EDAT- 2021/02/20 06:00
MHDA- 2021/07/01 06:00
CRDT- 2021/02/19 17:13
PHST- 2021/02/06 00:00 [revised]
PHST- 2020/11/29 00:00 [received]
PHST- 2021/02/16 00:00 [accepted]
PHST- 2021/02/20 06:00 [pubmed]
PHST- 2021/07/01 06:00 [medline]
PHST- 2021/02/19 17:13 [entrez]
AID - 10.1111/dom.14358 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2021 Jul;23(7):1471-1483. doi: 10.1111/dom.14358. Epub 2021 
      Mar 9.