publication . Article . Other literature type . 2015

Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial

Leffler, Daniel A.; Kelly, Ciaran P.; Green, Peter H.R.; Fedorak, Richard N.; DiMarino, Anthony; Perrow, Wendy; Rasmussen, Henrik; Wang, Chao; Bercik, Premysl; Bachir, Natalie M.; ...
Open Access
  • Published: 13 Feb 2015
  • Publisher: Elsevier BV
Abstract
Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days ( P = .017), a 31% increase in improved symptom days ( P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment ( P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness ( P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213.
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free text keywords: Gastroenterology, Hepatology, Article, Gastrointestinal agent, Internal medicine, medicine.medical_specialty, medicine, Clinical endpoint, Repeated measures design, Randomized controlled trial, law.invention, law, Gluten free, Placebo, Surgery, Gastroenterology, business.industry, business, Intention-to-treat analysis, Larazotide
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Other literature type . 2015
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