Arbaclofen placarbil decreases postprandial reflux in patients with gastroesophageal reflux disease.
OBJECTIVE
Arbaclofen placarbil (AP), previously designated as XP19986, is an investigational prodrug of the active R-isomer of baclofen, a gamma-aminobutyric acid agonist reflux inhibitor. The aim of this study was to assess the efficacy and safety of AP for decreasing meal-induced reflux episodes in patients with gastroesophageal reflux disease (GERD).


METHODS
We conducted a multicenter, randomized, double-blind, crossover study comparing single doses of AP with placebo. Different patients were enrolled at each of four escalating AP doses: 10, 20, 40, and 60 mg. Enrolled patients had GERD symptoms at least three times a week and 20 reflux episodes on impedance/pH monitoring over a period of 2 h. During study visits separated by periods of 3-7 days, patients received single doses of AP or placebo, followed by high-fat meals 2 and 6 h after treatment. The primary end point was the number of reflux episodes over 12 h after treatment.


RESULTS
A total of 50 patients were treated; efficacy analysis included 44 patients who received both AP and placebo and had technically satisfactory impedance/pH data. For the combined data from all dose cohorts, there was a statistically significant (P=0.01) decrease in reflux episodes over 12 h after treatment with AP compared with placebo. The mean (s.d.) number of reflux episodes over 12 h after AP treatment was 50.5 (27.2), with a mean reduction of 10.4 (23.9) episodes (17%) compared with placebo, for which a mean (s.d.) number of 60.9 (35.3) episodes was observed. Heartburn events associated with reflux were reduced during treatment with AP compared with placebo. AP seemed to be the most efficacious in the 60-mg dose group, and was well tolerated at all dose levels.


CONCLUSIONS
AP decreased reflux and associated symptoms with good tolerability in patients with GERD.
Gerson
Lauren B
LB
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California 94305-5202, USA. lgerson@stanford.edu
Huff
F Jacob
FJ
Hila
Amine
A
Hirota
William K
WK
Reilley
Sandra
S
Agrawal
Amit
A
Lal
Ritu
R
Luo
Wendy
W
Castell
Donald
D
D000328:Adult; D001418:Baclofen / Q000031:analogs & derivatives; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D050782:Esophageal pH Monitoring; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006356:Heartburn / Q000188:drug therapy; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D011355:Prodrugs / Q000627:therapeutic use*; D055815:Young Adult
D005765:Gastrointestinal Agents; D011355:Prodrugs; D001418:Baclofen; C543531:arbaclofen placarbil