Gastroesophageal Reflux Disease (GERD)
Conditions
Keywords
Gastroesophageal, Reflux, Disease, GERD
Brief summary
The purpose of this study is to compare the efficacy of rabeprazole extended release 50 mg (once daily) versus ranitidine 150 mg (twice daily) in the maintenance of complete healing in subjects with healed erosive gastroesophageal reflux disease (eGERD).
Detailed description
This is a multicenter, randomized, double-blind, double-dummy, parallel-group study. Subjects who meet all eligibility criteria will be randomly assigned to 1 of 2 treatment groups, rabeprazole extended release 50 mg (once daily) or ranitidine 150 mg (twice daily). Please note that this study is not a duplicate of E3810-G000-305; this is a separate study being conducted along with -305.
Interventions
DRUGRabeprazole ER
50 mg capsule, taken orally, once daily for 26 weeks.
DRUGRanitidine
150 mg capsule, taken orally, twice daily for 26 weeks.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
KEY INCLUSION CRITERIA: 1\. Prior completion of Study E3810-G000-302 or -303. Subjects will need to have healed erosive esophagitis (absence of esophageal mucosal breaks or erosions) confirmed by EGD and sustained resolution of heartburn at Visit 4 or 5 of Study E3810-G000-302 or -303. KEY
Exclusion criteria
1. Esophageal motility disorders (achalasia, scleroderma, or esophageal spasm). 2. Barrett's esophagus or esophageal stricture. 3. Use of prescription or non-prescription proton pump inhibitors (PPIs), histamine receptor antagonists (H2RA), antacids, sucralfate, misoprostol, prokinetics or drugs with significant anticholinergic effects throughout the study. 4. Subjects who require chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), oral steroids (\>= 20 mg/day prednisone or equivalent), or aspirin (-\>; 325 mg/day). 5. Significant hepatic, renal, respiratory, endocrine, hematologic, neurologic, psychiatric, or cardiovascular system abnormalities that would be likely to interfere with the conduct of the study, the interpretation of study results, or the health of the subject during the study. 6. Any condition that would make the subject, in the opinion of the Investigator or Sponsor, unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Maintenance of Complete Healing of eGERD at Week 26 | Baseline to Week 26 | eGERD (erosive gastroesophageal reflux disease) healing measured by the Time-to-Relapse of Oesophageal Erosions using an Esophagogastroduodenoscopy (EGD). Lesions were identified and graded using the following Los Angeles (LA) classification of Oesophagitis: Not Present: No breaks (erosions) in the oesophageal mucosa (however, edema, erythema, or friability may be present). Grade A: One or more mucosal breaks not more than 5mm in maximum length. Grade B: One or more mucosal breaks more than 5mm in maximum length, but not continuous between the tops of 2 mucosal folds. Grade C: Mucosal breaks continuous between the tops of 2 or more mucosal folds, but involving less than 75% of the esophageal circumference. Grade D: Mucosal breaks involving at least 75% of the esophageal circumference. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | Baseline to Week 26 | Heartburn or other GERD-associated symptoms (regurgitation, epigastric or chest pain, dysphagia, belching, bloating, early satiety, other) was based on a 4-point Likert scale that included the following: None (No symptoms); Mild (Awareness of symptoms but easily tolerated); Moderate (Discomforting symptom sufficient to cause interference with normal activities including sleep); Severe (Incapacitating symptom, inability to perform normal activities). |
Countries
United States
Participant flow
Recruitment details
Participants were eligible for this study if they had completed one of the healing studies (E3810-G000-302 or E3810-G000-303), had no evidence of oesophageal erosions, had sustained heartburn resolution, and had no record of any serious adverse event (SAE) related to study medication during the healing study.
Pre-assignment details
Out of 240 participants who were randomized in this study, 237 participants received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| RAN 150mg BID Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks. | 60 |
| RAB ER 50mg QD Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks. | 177 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lack of Efficacy | 5 | 4 |
| Overall Study | Lost to Follow-up | 6 | 9 |
| Overall Study | Other | 6 | 18 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | RAN 150mg BID | RAB ER 50mg QD | Total |
|---|---|---|---|
| Age, Customized | 47.5 Years STANDARD_DEVIATION 13.55 | 47.5 Years STANDARD_DEVIATION 12.06 | 47.5 Years STANDARD_DEVIATION 12.43 |
| Sex: Female, Male Female | 28 Participants | 88 Participants | 116 Participants |
| Sex: Female, Male Male | 32 Participants | 89 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 56 | 42 / 170 |
| serious Total, serious adverse events | 1 / 56 | 3 / 170 |
Outcome results
Primary
Percentage of Participants With Maintenance of Complete Healing of eGERD at Week 26
eGERD (erosive gastroesophageal reflux disease) healing measured by the Time-to-Relapse of Oesophageal Erosions using an Esophagogastroduodenoscopy (EGD). Lesions were identified and graded using the following Los Angeles (LA) classification of Oesophagitis: Not Present: No breaks (erosions) in the oesophageal mucosa (however, edema, erythema, or friability may be present). Grade A: One or more mucosal breaks not more than 5mm in maximum length. Grade B: One or more mucosal breaks more than 5mm in maximum length, but not continuous between the tops of 2 mucosal folds. Grade C: Mucosal breaks continuous between the tops of 2 or more mucosal folds, but involving less than 75% of the esophageal circumference. Grade D: Mucosal breaks involving at least 75% of the esophageal circumference.
Time frame: Baseline to Week 26
Population: Intent-to-Treat (ITT) Population - all randomized subjects who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAN 150mg BID | Percentage of Participants With Maintenance of Complete Healing of eGERD at Week 26 | 31.7 Percentage of Participants |
| RAB ER 50mg QD | Percentage of Participants With Maintenance of Complete Healing of eGERD at Week 26 | 88.4 Percentage of Participants |
Secondary
Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26
Heartburn or other GERD-associated symptoms (regurgitation, epigastric or chest pain, dysphagia, belching, bloating, early satiety, other) was based on a 4-point Likert scale that included the following: None (No symptoms); Mild (Awareness of symptoms but easily tolerated); Moderate (Discomforting symptom sufficient to cause interference with normal activities including sleep); Severe (Incapacitating symptom, inability to perform normal activities).
Time frame: Baseline to Week 26
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RAN 150mg BID | Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | Yes | 8.3 Percentage of Participants |
| RAN 150mg BID | Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | No | 16.7 Percentage of Participants |
| RAN 150mg BID | Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | Missing | 75 Percentage of Participants |
| RAB ER 50mg QD | Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | Yes | 53.7 Percentage of Participants |
| RAB ER 50mg QD | Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | No | 17.5 Percentage of Participants |
| RAB ER 50mg QD | Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 | Missing | 28.8 Percentage of Participants |