Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb;32(2):252-261.
doi: 10.1002/oby.23928. Epub 2023 Nov 2.

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

Jennifer L Miller  1 , Evelien Gevers  2 , Nicola Bridges  3 , Jack A Yanovski  4 , Parisa Salehi  5 , Kathryn S Obrynba  6 , Eric I Felner  7 , Lynne M Bird  8 , Ashley H Shoemaker  9 , Moris Angulo  10 , Merlin G Butler  11 , David Stevenson  12 , Anthony P Goldstone  13 , John Wilding  14 , Melissa Lah  15 , M Guftar Shaikh  16 , Elizabeth Littlejohn  17 , M Jennifer Abuzzahab  18 , Amy Fleischman  19 , Patricia Hirano  20 , Kristen Yen  20 , Neil M Cowen  20 , Anish Bhatnagar  20 ; C601/C602 Investigators
Affiliations

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

Jennifer L Miller et al. Obesity (Silver Spring). 2024 Feb.

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.

Trial registration: ClinicalTrials.gov NCT03440814 NCT03714373.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
CONSORT diagram for Long-Term Treatment with DCCR
Figure 2.
Figure 2.
HQ-CT Total Score Change from Baseline with DCCR Over 52 Weeks: Primary Endpoint (Overall ITT Population, blue line) and Participants with More Severe Hyperphagia (Baseline HQ-CT > 22, green line)
Figure 3.
Figure 3.
Exposure-Response Relationship for HQ-CT Change from Baseline at 13 Weeks in C601
Figure 4.
Figure 4.
Caregiver and Clinical Global Impression of Severity at Baseline (blue bars) and Following 52 Weeks of Treatment with DCCR (green bars)
See this image and copyright information in PMC

References

    1. Lionti T, Reid SM, White SM, Rowell MM. A population-based profile of 160 Australians with Prader-Willi syndrome: trends in diagnosis, birth prevalence and birth characteristics. Am J Med Genet A 2015; 167A(2):371–378. - PubMed
    1. Gillentine MA, Lupo PJ, Stankiewicz P, Schaaf CP. An estimation of the prevalence of genomic disorders using chromosomal microarray data. J Hum Genet 2018; 63(7):795–801. - PMC - PubMed
    1. Butler MG, Miller JL, Forster JL. Prader-Willi syndrome – Clinical genetics, diagnosis and treatment approaches: An update. Curr Pediatr Rev 2019; 15(4):207–244. - PMC - PubMed
    1. Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold J-A, Kimonis V, Dykens E, Butler MG, Shuster JJ, Driscoll DJ.. Nutritional phases in Prader-Willi syndrome. Am. J. Med. Genet. Part. A 2011, 155:1040–1049. - PMC - PubMed
    1. McCandless SE. Clinical Report-Health supervision for children with Prader-Willi syndrome. Pediatrics 2011; 127:195–204. - PubMed

Associated data

LinkOut - more resources