Open Label Study Evaluating Different Dosing Regimens of Rabeprazole in Gastro-esophageal Reflux Disease (GERD) Patients With Night-time Heartburn Symptoms.

Last updated: May 16, 2011
Sponsor: Janssen-Ortho Inc., Canada
Overall Status: Completed

Phase

3

Condition

Esophageal Disorders

Heartburn (Pediatric)

Heartburn

Treatment

N/A

Clinical Study ID

NCT00553449
CR005692
  • Ages > 18
  • All Genders

Study Summary

The purpose of this study is to evaluate the effect of each of the rabeprazole treatment regimens on nocturnal heartburn symptoms.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients must have had a minimum three-month history of symptomatic GERD, withheartburn as the predominant symptom, and must report nocturnal heartburn symptoms (i.e., heartburn symptoms experienced during the night-time period, between 2200 and 0600h)

  • Patients must currently be taking a proton-pump inhibitor (PPI) or histamine-2receptor antagonist (H2RA) at least four weeks prior to study admission

  • Patients must be able to read, write and understand the language of the HRQOL andproductivity assessment instruments (PAGI-SYM, PAGI-QOL, WPAI-GH) i.e., English orFrench

  • Patients must have been at least 80% compliant with their current acid suppressivetherapy, and must have completed a minimum of 11 of 14 nocturnal heartburn ratingsduring the run-in period (i.e. <=3 "missing" nocturnal heartburn ratings during the 14-day period)

  • Patients must have a total nocturnal heartburn symptom score of >4 points during the 2-week run-in period

  • 3 "missing" nocturnal heartburn ratings during the 14-day period) as recorded in thediary

  • Night-time heartburn control assessment of "very dissatisfied, dissatisfied, neitherdissatisfied nor satisfied" at the end of the 2-week run-in period.

Exclusion

Exclusion Criteria:

  • Patients currently taking rabeprazole 20mg once daily (morning or eveningadministration) or 10mg twice daily (morning and evening administration) on acontinuous basis

  • Documented evidence of GERD refractory to acid suppressive therapy (i.e.

  • no or poor clinical response to at least two treatment courses of 4-weeks durationwith a PPI)

  • Esophagitis known to be the result of systemic events (e.g. scleroderma, ingestedirritants)

  • Active GI bleeding, or presence of "alarm symptoms" (i.e., vomiting, blood in stool,anemia, dysphagia)

  • Documented history of significant pyloric stenosis or esophageal ring stricture

  • Documented evidence of esophageal or gastric varices

  • Patients with primary motility disorders, infectious or inflammatory conditions of thesmall or large intestine, malabsorption syndromes, GI obstruction, history ofgastrointestinal malignancy, definitive acid-lowering surgery or other esophageal,gastric or intestinal surgery (including vagotomy) except for simple closure ofperforation

  • Patients who are unable or unwilling to discontinue the use of prostaglandins (e.g.misoprostol), sucralfate, prokinetic agents (e.g. metoclopramide), anticholinergics,cholinergic agents or spasmolytics. Use of opiates may be continued if started atleast 2 weeks before study admission and the dosage is consistent (± 25% for totalopioid daily dose) throughout the study

  • Treatment with high-dose systemic corticosteroids (>10mg/day prednisone equivalent)and NSAIDs, including COX-2 selective inhibitors, cannot be initiated at anytimeduring the study. However, patients taking corticosteroids and NSAIDs (including ASA)before study entry may continue these medications during the study, however, they musthave been taking a stable dose (e.g. for oral medication, a consistent daily dose ± 25%) for at least 2 weeks before study admission and the dosage must be kept constantthroughout the study. Occasional, intermittent use of NSAIDs for acute, self-limitingconditions (e.g. headache relief) is acceptable during the study

  • >3 daytime episodes during any 7 consecutive days of the run-in period

  • >1 severe or very severe daytime episode (i.e., more than 1 daytime heartburn episoderated >=3) during any 7 consecutive days of the run-in period

  • Maximum total daytime heartburn score >5 during any 7 consecutive days of the run-inperiod.

Study Design

Total Participants: 48
Study Start date:
July 01, 2004
Estimated Completion Date:
September 30, 2005

Study Description

There is limited data regarding the estimate of patients who experience nocturnal symptoms despite adequate daytime heartburn control, the incidence and severity of nocturnal heartburn episodes after a minimum of 4 weeks of acid suppressive therapy with a Proton-pump inhibitor (PPI) or Histamine -2-receptor antagonist (H2RA), and the effect of instituting rabeprazole therapy after failure to control nocturnal heartburn symptoms with other acid suppressive therapy. This is a multicentre, randomised (study medication is assigned by chance), controlled, parallel-group, open-label study in GERD patients. Patients will be screened and enter a 2-week run-in phase to document heartburn symptoms while on their current therapy, during which they will complete a daily diary of symptoms and antacid use. Patients who have troublesome nocturnal heartburn episodes, but adequate daytime heartburn symptom control (as defined) will enter an 8-week treatment phase where they are randomised to one of the rabeprazole regimens: 20mg once daily in the evening (dose administered 30minutes prior to the evening meal; "QPM" regimen), 10mg twice daily (dose administered 30minutes prior to the morning and evening meals; "BID/twice daily" regimen) or 20mg once daily in the morning (dose administered 30minutes prior to the morning meal; "QAM/every morning" regimen), plus antacids as required. The study hypothesis is that after failure to control night-time heartburn symptoms with other acid suppressive therapy, instituting rabeprazole will have a beneficial effect. Safety assessments include: physical examination and pregnancy test at screening, vital signs and weight at randomization and final visit, adverse event and concomitant medication reporting at every visit. Rabeprazole 20mg once daily in the evening: one rabeprazole 20mg tablet daily in the evening, 30-60 minutes before dinner for 56 days OR Rabeprazole 10mg twice daily: one rabeprazole 10mg tablet in the morning, 30-60 minutes before breakfast, and one rabeprazole 10mg tablet 30-60 minutes before dinner for 56 days. OR Rabeprazole 20mg once daily in the morning: one rabeprazole 20mg tablet daily in the morning, 30-60 minutes before breakfast for 56 days.