ECE2022 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (202 abstracts)
Comparison of hyperphagia and problem behaviors in participants with prader-willi syndrome (PWS) receiving diazoxide choline extended-release (DCCR) with matched participants in PATH for PWS (PfPWS)
Evelien Gevers 1 , Theresa Strong 2,3 , Jennifer Miller 4 , Eric Felner 5 , Tony Goldstone 6 , Nicola Bridges 7 , Jack Yanovski 8 , Lynne Bird 9 , Merlin Butler 10 , Kathryn Obrynba 11 , Melissa Lah 12 , Ashley Shoemaker 13 , Jorge Mejia-Corletto 14,15 , David Stevenson 16 , John Wilding 17 , Virginia Kimonis 18 , Jennifer Abuzzahab 19 , Laura Konczal 20 , Verghese Mathew 21 , Neil Cowen 22 , Michael Woloschak 22 & Anish Bhatnagar 22
1Queen Mary University of London, Barts Health NHS Trust, London, United Kingdom; 2Foundation for Prader-Willi Research, Walnut, United States; 3PATH for PWS Investigators; 4University of Florida, Gainesville, United States; 5Emory Children’s Center, Druid Hills, United States; 6Hammersmith Hospital, London, United Kingdom; 7Chelsea and Westminster Hospital, London, United Kingdom; 8National Institutes of Health, Bethesda, United States; 9Rady Children’s Hospital - San Diego, San Diego, United States; 10Kansas University Medical Center, Kansas City, KS, United States; 11The Research Institute at Nationwide Children’s Hospital, Columbus, United States; 12Indiana University School of Medicine, Indianapolis, United States; 13Vanderbilt University, Nashville, United States; 14NYU Winthrop Hospital, Mineola, United States; 15NYU Langone Hospital-Long Island, Pediatrics, Division of Pediatric Endocrinology, Mineola,; 16Stanford University, Palo Alto, United States; 17University of Liverpool, Liverpool, United Kingdom; 18University of California Irvine, Irvine, United States; 19Children’s Minnesota, Saint Paul, United States; 20 UH Cleveland Medical Center, Cleveland, United States; 21 Hull and East Yorkshire Hospitals NHS Trust, Hull, United Kingdom; 22 Soleno Therapeutics, Inc., Redwood City, United States
Background: PWS is a rare neurodevelopmental genetic disorder characterized by hyperphagia, obesity, hormonal deficiencies, and problem behaviors for which there are no approved treatment. DCCR administration (100-525 mg/day) up to 52 weeks in participants with PWS improved hyperphagia, behavior, body composition and metabolic markers.
Objective: The objective of this study was to compare changes in hyperphagia (using Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and PWS-related behaviors (via PWS Profile Questionnaire [PWS-P]) between 114 participants enrolled in DCCR placebo-controlled, double-blind (C601, NCT03440814) and open-label extension (C602, NCT03714373) studies (sponsored by Soleno Therapeutics) and a matched sub-cohort from PfPWS sponsored by Foundation for Prader Willi Research, NCT03718416) (n=229) who did not receive experimental treatment.
Methods: C601/C602 and PfPWS studies were conducted concurrently. The creation of the PfPWS sub-cohort was conducted prospectively by an independent group prior to receiving the results from either study. Participants from both groups had genetically confirmed PWS and their caregivers completed the HQ-CT and PWS-P questionnaires prior to enrollment. Availability of participant-level data in PfPWS allowed for the creation of a propensity matched control cohort (n=195) similar to the C601/C602 study population by applying the defined inclusion criteria (age, gender, baseline HQ-CT score, baseline weight, and data collection time points).
Results: Statistically significant reductions in HQ-CT score for C601/C602 compared to PfPWS sub-cohort at Week 26 were observed for propensity-adjusted [Difference (C601/C602 – PfPWS), Adjusted Least-Square means, SE (standard error), 2-sided 95% CI=-5.7 (-7.43, -3.95)] and non-propensity-adjusted analyses [Difference=-5.9 (-7.53, -4.34)] (all P<0.001), which were sustained at Week 52 [Difference (C601/C602 - PfPWS)=-5.5 (-7.39, -3.64) for propensity-adjusted;=-5.9 (-7.65, -4.23) for non-propensity-adjusted; (all P<0.001)]. The difference in HQ-CT score between the two cohorts was consistent across age, sex, baseline HQ-CT, PWS genotype, geographical subgroups and growth hormone use. Reduction of PWS-P scores for C601/C602 were statistically significant across all domains (aggression, anxiety, rigidity/irritability, compulsivity, depression, disordered thinking) in comparison to PfPWS sub-cohort (P<0.001 for all) at Week 26 and were maintained at Week 52 (P<0.001 to 0.03).
Conclusions: These data demonstrate that improvements in hyperphagia and other PWS-related behaviors achieved by 26 weeks and maintained through 52 weeks in subjects receiving DCCR were significantly greater than in matched controls from an untreated observational cohort, in line with previous results of C601/C602 studies. This further suggests that DCCR may be an effective treatment option for individuals with PWS.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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