Diazoxide Choline Extended-release Tablets in Prader-Willi Syndrome: A Randomized, Double-blind, Withdrawal Period Study

Clinical Snapshot

Key Findings

• P Value: P = 0.0022 for primary endpoint

• Effect Size: Moderate effect size for hyperphagia reduction with continued DCCR treatment

• Primary Outcome: HQ-CT total score change: placebo +7.6 (SE 1.09) vs DCCR +2.6 (SE 1.12), difference 5.0 points

• Nnt Or Sensitivity: NNT not calculable from available data; effect size suggests clinical benefit in majority of patients

• Confidence Interval: Weight difference: -1.6 kg (95% CI: -3.1, -0.1); BMI z-score difference: -0.09 (95% CI: -0.17, -0.01)

Clinical Application

Requires specialist endocrine/genetic medicine oversight; once-daily dosing enhances compliance Would require TGA approval and PBS listing consideration; aligns with RACGP rare disease management principles; specialist centers in major cities could coordinate care Children ≥4 years and adults with genetically confirmed Prader-Willi syndrome and problematic hyperphagia

Abstract

CONTEXT: The hallmark condition of Prader-Willi syndrome, a rare, genetic neurobehavioral/metabolic disorder, is life-threatening hyperphagia. OBJECTIVE: We assessed the efficacy and safety of diazoxide choline extended-release (DCCR) tablets for the treatment of hyperphagia in adults and children four years of age and older with Prader-Willi syndrome. METHODS: We conducted a 16-week, randomized withdrawal study in children and adults with Prader-Willi syndrome and hyperphagia. Participants who previously completed randomized (13-week DCCR or placebo) and open-label (2.5-4.5 years DCCR) studies were randomized 1:1 to receive once-daily DCCR or placebo. The primary endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score change from baseline to 16 weeks. Secondary endpoints included Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I); exploratory endpoints included weight and body mass index (BMI) z-score. RESULTS: Seventy-seven participants were randomized (DCCR:38; placebo:39). Statistically significant increases in HQ-CT from baseline to week 16 were observed with placebo vs DCCR [least square (LS) mean (standard error) change 7.6 (1.09)] with placebo and 2.6 (1.12) with DCCR; P = .0022. CGI scores favored DCCR but were not significantly changed. Consistent with the hyperphagia response, the placebo cohort gained more weight and increased their BMI z-score more than the DCCR cohort [LS mean weight difference (95% confidence interval) -1.6 kg (-3.1, -0.1)]; LS mean z-score difference was -0.09 (-0.17, -0.01). Adverse events were similar with both treatments, with no serious adverse events in the DCCR arm. CONCLUSION: Continued DCCR treatment was superior to placebo for hyperphagia. DCCR appears to offer meaningful therapeutic benefits for people with Prader-Willi syndrome.

References

1. 1.Miller, J. L., Bridges, N., Felner, E. I., Salehi, P., Yanovski, J. A., Stevenson, D. A., Mejia-Corletto, J., Shaikh, M. G., Abuzzahab, M. J., Fleischman, A., Kimonis, V., Shoemaker, A. H., Holland, A., Bird, L. M., Obrynba, K. S., Lah, M., Littlejohn, E., Harwood, K., Shea, H., Viskochil, D., Hirano, P., Yen, K., Ballal, S., Huang, M., Cowen, N. M., Bhatnagar, A., & Gevers, E. (2026). Diazoxide choline extended-release tablets in Prader-Willi syndrome: A randomized, double-blind, withdrawal period study. *The Journal of Clinical Endocrinology and Metabolism*. https://doi.org/10.1210/clinem/dgaf661