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 health care 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 endpoint 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 group (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% confidence interval, 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, Number: NCT02637557).

A randomized trial of polyunsaturated fatty acids for refractory epilepsy.

OBJECTIVE: Though polyunsaturated fatty acids (PUFA) reduce seizures in several animal models, results have been inconsistent in humans. The goal of the present study was to assess the effectiveness of a PUFA supplement as adjunctive treatment for intractable focal or generalized epilepsy in humans. METHODS: Adults with uncontrolled epilepsy were randomized to either mineral oil placebo or a PUFA supplement (eicosapentanoic acid (EPA) plus docosahexanoic acid (DHA), 2.2 mg/day in a 3:2 ratio). Following a 4-week prospective baseline and 1-week titration, subjects entered a 12-week treatment period, followed by an optional 4-week open-label phase. RESULTS: Of 21 subjects (12 PUFA and 9 placebo), 0 on PUFA versus 2 on placebo had at least a 50% decrease in seizure frequency from baseline (P=0.17). Overall, seizure frequency increased 6% on PUFA and decreased 12% on placebo (P=0.21). During optional open-label administration, however, 15 of 19 subjects had fewer seizures than during baseline (P=0.02). CONCLUSIONS: Based on the randomized, blinded portion of this study, the PUFA preparation used was not superior to placebo as adjunctive treatment for intractable epilepsy. It is not known whether different doses or different EPA:DHA ratios would be effective.