Gastroesophageal Reflux Disease
Conditions
Keywords
non-erosive symptomatic GERD, GERD
Brief summary
The purpose of this study to determine the efficacy of 20 mg of rabeprazole given as a maintenance intermittent therapy following acute treatment for Symptomatic Gastroesophageal Reflux Disease (s-GERD).
Interventions
rabeprazole sodium tablet 20 mg once daily
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female patients, 18 to 65 years of age. 2. If female, not of childbearing potential by reason of surgery, radiation or menopause, or of childbearing potential, but using an approved method of contraception since the last menstrual period, for example, intrauterine device (IUD), implant, double barrier method, or oral contraceptives for at least one cycle. Females of childbearing potential must have a negative urine pregnancy test before medication is dispensed. 3. Patients must report a minimum three-month history of GERD symptoms. GERD symptoms are defined as heartburn with or without regurgitation or other associated GERD symptoms. 4. Patients must have at least 4 days with heartburn per week in each of the 2 weeks prior to Screening. 5. Patients must have no esophagitis, with no proton pump inhibitors (PPIs, prescription or OTC), H2 blockers (prescription or OTC) or prokinetics within 14 days, prior to the endoscopy. Key
Exclusion criteria
1. Evidence of significant hepatic, renal, respiratory, endocrine, hematologic, neurologic, psychiatric or cardiovascular system abnormalities, unless the Sponsor and Investigator agree that the nature and severity of any abnormality is unlikely to interfere with the conduct of the study, the interpretation of study results, or the health of the patient during the study. 2. Females must not be pregnant, lactating or have a positive urine eta human chorionic gonadotropin (B-hCG) laboratory result. 3. Patients with a history of allergy or sensitivity to proton pump inhibitors or to their inactive ingredients. 4. Patients with known gastric ulcer, duodenal ulcer, infectious or inflammatory conditions of the small or large intestine, malabsorption syndromes, obstruction, a history of gastrointestinal malignancy, or prior gastric or intestinal surgery (including vagotomy). 5. Patients who have a history of Barrett's esophagus, esophageal stricture, or pyloric stenosis. 6. Patients with a history of endoscopically-proven esophagitis any time in the past. 7. Patients who have taken proton pump inhibitors (PPIs, prescription or OTC), H2 blockers (prescription or OTC) or prokinetics within 14 days, prior to Screening endoscopy, or any of these medications within 7 days prior to the single-blind placebo run-in period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population). | 6 months double-blind maintenance phase | The percentage of heartburn-free days during the 6-month Maintenance Treatment Phase in patients treated with rabeprazole 20 mg compared to patients who received placebo in the ITT Population. Heartburn-free day was defined as no heartburn in both the daytime and nighttime period on a given day. Note a total 388 subjects were enrolled at the beginning of Acute Phase and 200 subjects were enrolled into the double-blind 6-month maintenance treatment phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percent of Heartburn-free Daytime Period During the 6-month Maintenance Treatment Phase | 6-month maintenance phase | The percentage of heartburn-free daytime period is presented cumulatively including all data collected during the 6-month Maintenance Phase |
| The Percent of Heartburn-free Nighttime Period During the 6-month Maintenance Treatment Phase | 6-month maintenance phase | The percentage of heartburn-free nighttime period is presented cumulatively including all data collected during the 6-month |
Countries
United States
Participant flow
Recruitment details
This study was recruited at 47 centers in the US during the period of 7-Oct-2004 and 12-Dec-2005.
Pre-assignment details
After enrollment and before randomization (treatment assignment), there was a 2-week placebo run-in phase followed by a 4-week open-label Acute Phase during which subjects were treated with rabeprazole 20 mg once daily for the treatment of heartburn. Note the below participant flow is based on Safety Population (total 200 subjects).
Participants by arm
| Arm | Count |
|---|---|
| Rabeprazole 20 mg Orally, once daily for 7 to 14-day courses intermittently during the 6-month Maintenance Treatment Phase (ITT population). | 96 |
| Placebo Orally, once daily for 7 to 14-day courses intermittently during the 6-month Maintenance Treatment Phase (ITT population). | 91 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lack of Efficacy | 6 | 33 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Medication Noncompliance | 1 | 1 |
| Overall Study | Other | 3 | 5 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | Rabeprazole 20 mg |
|---|---|---|---|
| Age Continuous | 46.6 years STANDARD_DEVIATION 11.69 | 46.3 years STANDARD_DEVIATION 11.66 | 46.0 years STANDARD_DEVIATION 11.67 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 19 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 28 Participants | 12 Participants |
| Race (NIH/OMB) White | 64 Participants | 138 Participants | 74 Participants |
| Sex: Female, Male Female | 59 Participants | 123 Participants | 64 Participants |
| Sex: Female, Male Male | 32 Participants | 64 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / — | 36 / — |
| serious Total, serious adverse events | 2 / — | 2 / — |
Outcome results
Primary
The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population).
The percentage of heartburn-free days during the 6-month Maintenance Treatment Phase in patients treated with rabeprazole 20 mg compared to patients who received placebo in the ITT Population. Heartburn-free day was defined as no heartburn in both the daytime and nighttime period on a given day. Note a total 388 subjects were enrolled at the beginning of Acute Phase and 200 subjects were enrolled into the double-blind 6-month maintenance treatment phase.
Time frame: 6 months double-blind maintenance phase
Population: Intent-to-treat (ITT) population, total 187 subjects, was used for efficacy analyses. Safety population (total 200 subjects) was used for safety analysis and participant flow.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rabeprazole 20 mg | The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population). | 82.58 Percentage of Days | Standard Deviation 14.39 |
| Placebo | The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population). | 62.17 Percentage of Days | Standard Deviation 29.93 |
Comparison: Efficacy analyses were based on the intent-to-treat (ITT) population, which was comprised of all patients in the safety-evaluable population who had a baseline and ≥1 post-randomization primary efficacy endpoint evaluation and who had received ≥1 dose of study medication during the maintenance phase.p-value: <0.0001t-test, 2 sided
Secondary
The Percent of Heartburn-free Daytime Period During the 6-month Maintenance Treatment Phase
The percentage of heartburn-free daytime period is presented cumulatively including all data collected during the 6-month Maintenance Phase
Time frame: 6-month maintenance phase
Secondary
The Percent of Heartburn-free Nighttime Period During the 6-month Maintenance Treatment Phase
The percentage of heartburn-free nighttime period is presented cumulatively including all data collected during the 6-month
Time frame: 6-month maintenance phase