Safety and Efficacy of Delayed Release Rabeprazole in 1- to 11-Month-Old Infants With Symptomatic GERD

Hussain, Sunny*; Kierkus, Jaroslaw; Hu, Peter; Hoffman, Diane; Lekich, Ray; Sloan, Sheldon; Treem, William

Journal of Pediatric Gastroenterology & Nutrition: February 2014 - Volume 58 - Issue 2 - p 226–236
doi: 10.1097/MPG.0000000000000195
Original Articles: Gastroenterology

Aim: The efficacy and safety of rabeprazole, a proton pump inhibitor, were studied in infants with gastroesophageal reflux disease (GERD).

Methods: Infants ages 1 to 11 months, with symptomatic GERD resistant to conservative therapy and/or previous exposure to acid-suppressive medications, were screened. After scoring >16 on a GERD symptom score (Infant Gastroesophageal Reflux Questionnaire-Revised [I-GERQ]), 344 infants were enrolled in a 1- to 3-week open-label (OL) phase and received rabeprazole 10 mg/day. Following caregiver-rated clinical improvement during the OL phase, patients were randomized to placebo, rabeprazole 5 mg, or rabeprazole 10 mg in the ensuing 5-week double-blind (DB) withdrawal phase. Primary endpoints evaluated from DB baseline to the end of the DB withdrawal phase included frequency of regurgitation, weight-for-age z score, and daily and weekly GERD symptom scores.

Results: Overall, 231 (86%) of the 268 randomized infants (placebo: 90; rabeprazole 5 mg: 90; rabeprazole 10 mg: 88) completed the study. Efficacy endpoints were similarly improved during the OL phase in all of the groups, and continued improving during the DB withdrawal phase with no difference between the placebo and combined rabeprazole groups. Mean decrease in frequency of regurgitation (−0.79 vs −1.20 times per day; P = 0.168), in I-GERQ-Revised scores (−3.6 [−25%] vs −3.9 points [−27%]; P = 0.960), in I-GERQ-Daily Diary scores (−1.87 [−19%] vs −1.85 [−19%]; P = 0.968), and increase in weight-for-age z scores (mean [standard deviation]: 0.11 [0.329] vs 0.14 [0.295]; P = 0.440) indicated equal improvement. Equal percentages (47%) reported adverse events in placebo and combined rabeprazole groups, with no new safety signals emerging.

Conclusions: In those infants with GERD who improved with rabeprazole during the OL phase, improvements in symptoms and weight were similar in those who continued rabeprazole and those withdrawn to placebo during a 5-week DB phase.

*WK Pediatric Gastroenterology & Research, Shreveport, LA

Instytut “Pomnik-Centrum Zdrowia Dziecka,” Warsaw, Poland

Janssen Research & Development, LLC, Raritan, NJ.

Address correspondence and reprint requests to William Treem, MD, Pediatric Center of Excellence, Janssen Research & Development, LLC, 920 US Highway 202, Raritan, NJ 08869 (e-mail: wtreem@its.jnj.com).

Received 2 January, 2013

Accepted 30 September, 2013

www.clinicaltrials.gov registration no.: NCT00992589.

This study was financially supported by Janssen Research & Development, LLC (previously known as Johnson & Johnson Pharmaceutical Research & Development, LLC) and Eisai Medical Research, Inc. The sponsor also provided a formal review of this manuscript.

This article was presented in poster form at NASPGHAN 2012, October 18–21, 2012.

P.H., S.S., W.T., and D.H. are employees of Janssen Research & Development, LLC. R.L. is a consultant to Janssen Research & Development, LLC. The other authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,