Diazoxide choline extended‐release tablet in people with Prader‐Willi syndrome: results from long‐term open‐label study

Miller, J. L. et al. (2024) Diazoxide choline extended‐release tablet in people with Prader‐Willi syndrome: results from long‐term open‐label study. Obesity, 32(2), pp. 252-261. (doi: 10.1002/oby.23928) (PMID:37919617)

Abstract

Objective: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). Methods: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. Results: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] −9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). Conclusions: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.

• Item Type: Articles
• Additional Information: Funding information: Funding for clinical trials C601 (ClinicalTrials.gov numbers NCT03440814) and C602 (NCT03714373) provided by Soleno Therapeutics.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shaikh, Dr Mohammed Guftar
• Authors: Miller, J. L., Gevers, E., Bridges, N., Yanovski, J. A., Salehi, P., Obrynba, K. S., Felner, E. I., Bird, L. M., Shoemaker, A. H., Angulo, M., Butler, M. G., Stevenson, D., Goldstone, A. P., Wilding, J., Lah, M., Shaikh, M. G., Littlejohn, E., Abuzzahab, M. J., Fleischman, A., Hirano, P., Yen, K., Cowen, N. M., and Bhatnagar, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Obesity
• Publisher: Wiley
• ISSN: 1930-7381
• ISSN (Online): 1930-739X
• Published Online: 02 November 2023
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Obesity 32(2):252-261
• Publisher Policy: Reproduced under a creative commons licence