The Journal of clinical endocrinology and metabolism · 2026
Diazoxide Choline Extended-release Tablets in Prader-Willi Syndrome: A Randomized, Double-blind, Withdrawal Period Study.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Miller Jennifer L, Bridges Nicola, Felner Eric I, Salehi Parisa, Yanovski Jack A, Stevenson David A, Mejia-Corletto Jorge, Shaikh Mohamad G, Abuzzahab M Jennifer, Fleischman Amy, Kimonis Virginia, Shoemaker Ashley H, Holland Anthony, Bird Lynne M, Obrynba Kathryn S, Lah Melissa, Littlejohn Elizabeth, Harwood Katerina, Shea Heidi, Viskochil David, Hirano Patricia, Yen Kristen, Ballal Shaila, Huang Michael, Cowen Neil M, Bhatnagar Anish, Gevers Evelien
Аннотация
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.
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.