DESTINY PWS
Trial question
What is the effect of extended-release diazoxide choline on hyperphagia in patients with Prader-Willi syndrome?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
56.0% female
44.0% male
N = 124
124 patients (69 female, 55 male).
Inclusion criteria: patients aged ≥ 4 years with Prader-Willi syndrome and hyperphagia.
Key exclusion criteria: body weight < 20 or > 135 kg; pregnancy or lactation; any disease and/or condition which would prevent the patient from completing all study visits and assessments required by the protocol; participation in an interventional clinical study within the past 3 months.
Interventions
N=82 diazoxide choline ER (at a target dose of 3.3-5.8 mg/kg per day, titrated within 6 weeks, for 13 weeks).
N=43 placebo (matching placebo for 13 weeks).
Primary outcome
Least-square mean reduction in hyperphagia, as assessed by Hyperphagia Questionnaire for Clinical Trials, in the prespecified analysis
9.67
4.26
9.7
7.3
4.8
2.4
0.0
Diazoxide choline
ER
Placebo
Significant
increase ▲
Significantly greater reduction in least-square mean hyperphagia, as assessed by the Hyperphagia Questionnaire for Clinical Trials, in the prespecified analysis (9.67 vs. 4.26; AD 5.41 , 95% CI 1.19 to 9.63).
Secondary outcomes
No significant difference in least-square mean reduction in hyperphagia, as assessed by the Hyperphagia Questionnaire for Clinical Trials, in the intention-to-treat analysis (5.94 vs. 4.27; AD 1.67 , 95% CI -0.87 to 4.21).
Significant increase in patients regarded as minimally or much improved on Clinical Global Impression of Improvement (36.7% vs. 4.9%; AD 31.8%, 95% CI 3.21 to 60.39).
No significant difference in patients regarded as little, moderately, or very much better on Caregiver Global Impression of Change (39% vs. 28.5%; AD 10.5%, 95% CI -14.04 to 35.04).
Safety outcomes
Significant differences in hypertrichosis (35.7% vs. 14.3%, peripheral edema (20.2% vs. 9.5%), and hyperglycemia (11.9% vs. 0%).
Conclusion
In patients aged ≥ 4 years with Prader-Willi syndrome and hyperphagia, diazoxide choline ER was superior to placebo with respect to a least-square mean reduction in hyperphagia, as assessed by the Hyperphagia Questionnaire for Clinical Trials, in the prespecified analysis.
Reference
Jennifer L Miller, Evelien Gevers, Nicola Bridges et al. Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1676-1685.
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