Arbaclofen Placarbil Decreases Reflux With Good Tolerability in Patients With Gastroesophageal Reflux Disease (Am J Gastroenterol 2010;105:1266-1275)

Abstract

Arbaclofen placarbil (AP), previously designated as XP19986, is a novel transported prodrug of the active R-isomer of baclofen, which overcomes the pharmacokinetic limitations of racemic baclofen.1 AP is efficiently absorbed by high-capacity active transport pathways expressed throughout the gastrointestinal (GI) tract, and rapidly metabolized to release R-baclofen after the absorption. This multicenter, randomized, double-blind, crossover study comparing single doses of AP with placebo was conducted to assess the efficacy and safety of AP for decreasing meal-induced reflux episodes in patients with gastroesophageal reflux disease (GERD).2 Different patients were enrolled at each of 4 escalating AP doses: 10, 20, 40 and 60 mg. A total of 50 patients were treated and the efficacy analysis included 44 patients who completed the protocol and had technically satisfactory impedance/pH data. There was a statistically significant decrease in reflux episodes over 12 hours after treatment with AP compared with placebo (p = 0.01). The mean ± SD number of reflux episodes over 12 hours after AP treatment was 50.5 ± 27.2, with a mean reduction of 10.4 ± 23.9 episodes (17%) compared with placebo (60.9 ± 35.3). Only acid reflux episodes were statistically decreased after treatment with AP. Heartburn events associated with reflux were reduced during treatment with AP compared with placebo (12.9 ± 11.9 vs 16.7 ± 18.2, p = 0.03). AP seemed to be the most efficacious in the 60 mg dose group, and was well tolerated at all dose levels.