Miller, Jennifer L, Gevers, Evelien, Bridges, Nicola, Yanovski, Jack A, Salehi, Parisa, Obrynba, Kathryn S, Felner, Eric I, Bird, Lynne M, Shoemaker, Ashley H, Angulo, Moris et al (show 9 more authors)
(2023)
Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 108 (7).
pp. 1676-1685.
Abstract
<h4>Context</h4>Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled.<h4>Objective</h4>The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones.<h4>Methods</h4>In DESTINY PWS, a 13-week, randomized, double-blind, placebo-controlled, phase 3 trial, 127 participants with PWS aged 4 years and older with hyperphagia were randomly assigned 2:1 to diazoxide choline extended-release tablet (DCCR) or placebo.<h4>Results</h4>DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012). Two of 3 secondary end points were improved (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). In an analysis of results generated pre-COVID, the primary (HQ-CT; P = .037) and secondary end points were all improved (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant).<h4>Conclusion</h4>DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis. DCCR treatment was associated with significant improvements in body composition and clinician-reported outcomes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Prader-Willi syndrome, hyperphagia, DCCR |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 29 Sep 2023 11:08 |
| Last Modified: | 29 Sep 2023 11:08 |
| DOI: | 10.1210/clinem/dgad014 |
| Open Access URL: | https://doi.org/10.1210/clinem/dgad014 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173224 |
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