Language

English

Publication Date

6-16-2023

Journal

The Journal of Clinical Endocrinology & Metabolism

DOI

10.1210/clinem/dgad015

PMID

36633570

PMCID

PMC10271225

PubMedCentral® Posted Date

1-12-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Context: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy.

Objective: To evaluate safety and efficacy of intranasal carbetocin in PWS.

Design: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up.

Setting: Twenty-four ambulatory clinics at academic medical centers.

Participants: A total of 130 participants with PWS aged 7 to 18 years.

Interventions: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose.

Main outcome measures: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C).

Results: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing.

Conclusions: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS.

Keywords

Child, Humans, Prader-Willi Syndrome, Oxytocin, Pandemics, COVID-19, Hyperphagia, Anxiety, Prader-Willi syndrome, carbetocin, oxytocin, vasopressin, hyperphagia, anxiety

Comments

Clinical trials registration number: NCT03649477.

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.