An Innovative Disease-Drug-Trial Framework to Guide Binge Eating Disorder Drug Development: A Case Study for Topiramate
JournalClinical and Translational Science
PublisherBlackwell Publishing Ltd
MetadataShow full item record
AbstractAs with other psychiatric disorders, development of drugs to treat binge-eating disorder (BED) has been hampered by high placebo response and dropout rates in randomized controlled trials (RCTs). Although not approved for use in BED, several RCTs have suggested that topiramate is efficacious for BED in obese individuals. Using data from a positive investigator-initiated RCT of topiramate in 61 obese individuals with BED, the objective of the present study is (i) to develop a quantitative disease-drug-trial framework to inform future BED clinical trial designs, and (ii) to determine the optimal topiramate dose to achieve therapeutic efficacy. Disease-drug-trial models were developed separately for the two efficacy measures, namely, longitudinal normalized weekly binge-eating episode frequency (BEF) and binge day frequency (BDF). Model building consisted of (i) developing a placebo effect model that describes response from the placebo group, (ii) adding a drug effect to the placebo model to describe dose-response relationships, and (iii) developing a parametric time to event model to characterize patient dropout patterns. The placebo effect on normalized BEF and BDF over time demonstrated a maximum decrease of ~ 57% by 5 weeks. Participants had a higher dropout probability if no weight loss occurred during the trial period. The identified dose-response relationship demonstrated a daily dose of 125 mg was needed to exhibit a marked reduction in weekly BEF. The developed comprehensive disease-drug-trial model will be utilized to simulate different clinical trial designs to increase the success for future BED drug development programs. Copyright 2019 The Authors.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85071951672&doi=10.1111%2fcts.12682&partnerID=40&md5=831e31479a502f7360104eea18babb26; http://hdl.handle.net/10713/10860
- A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa.
- Authors: Safer DL, Adler S, Dalai SS, Bentley JP, Toyama H, Pajarito S, Najarian T
- Issue date: 2020 Feb
- Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.
- Authors: Dalai SS, Adler S, Najarian T, Safer DL
- Issue date: 2018 Jan
- Double-blind, randomized, placebo-controlled trial of topiramate plus cognitive-behavior therapy in binge-eating disorder.
- Authors: Claudino AM, de Oliveira IR, Appolinario JC, Cordás TA, Duchesne M, Sichieri R, Bacaltchuk J
- Issue date: 2007 Sep
- Topiramate in the treatment of binge eating disorder associated with obesity: a randomized, placebo-controlled trial.
- Authors: McElroy SL, Arnold LM, Shapira NA, Keck PE Jr, Rosenthal NR, Karim MR, Kamin M, Hudson JI
- Issue date: 2003 Feb