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IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial.

BACKGROUND AIMS
Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the healthcare system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy.


METHODS
We performed a multicenter, double-blind, placebo-controlled trial from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary end point was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score.


RESULTS
Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 groups (dose-response P=.02). The treatment difference was 11.9% between the 1500-mg IW-3718 and placebo groups (P=.04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500-mg IW-3718 vs placebo groups was a reduction of 17.5% (95% CI, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events.


CONCLUSIONS
In a randomized trial of patients with refractory GERD, adding 1500-mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. ClinicalTrials.gov no: NCT02637557.