Gastroesophageal Reflux Disease (GERD)
Conditions
Keywords
GERD, erosive GERD, erosive esophagitis
Brief summary
The purpose of this study is to investigate the efficacy and safety of Rabeprazole (RAB) Extended-Release (ER) 50 mg versus Esomeprazole (ESO) 40 mg in subjects with erosive gastroesophageal reflux disease (eGERD).
Detailed description
This is a multicenter, randomized, double-blind, double-dummy, parallel-group study. Subjects who meet all the inclusion/exclusion criteria will be randomly assigned to 1 of 2 treatment groups, Rabeprazole Extended-Release (RAB ER) 50 mg or Esomeprazole (ESO) 40 mg for the treatment of mild to moderate erosive Gastroesophageal Reflux Disease (GERD).
Interventions
DRUGRabeprazole sodium
Rabeprazole ER 50 mg capsule, once daily for 4-8 weeks.
DRUGEsomeprazole
Esomeprazole 40 mg capsule, once daily for 4-8 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. Male or female, ages 18 to 75 years. 2. History of gastroesophageal reflux disease (GERD) symptoms for at least 3 months immediately before screening. 3. Heartburn for at least 2 days a week for at least 1 month before screening. 4. Esophageal erosions of Los Angeles (LA) Grades A or B based on EGD taken within 14 days prior to enrollment. 5. Subjects who are H. pylori negative based on a screening test. 6. Females should be either of non-childbearing potential or of childbearing potential. Females of childbearing potential must have negative pregnancy tests prior to randomization. Female subjects of childbearing potential must agree to use medically acceptable methods of contraception. 7. Subjects must be able to read, write, and understand the language of the symptom diary. KEY
Exclusion criteria
1. Current or a history of esophageal motility disorders. 2. Current or a history of Barrett's esophagus. Current esophageal strictures or esophagitis (known or suspected to be due to etiology other than GERD such as infection or medications). 3. Current or a history of Zollinger-Ellison syndrome and other acid hypersecretory conditions, or current gastric or duodenal ulcer. 4. Current or a history of cancer, with the exception of fully excised skin basal cell carcinoma. 5. Inflammatory bowel disease. 6. Unstable diabetes mellitus. 7. History of esophageal, gastric and duodenal surgery except simple suturing of an ulcer. 8. Subjects who require daily use of nonsteroidal anti-inflammatory drugs (NSAIDs), oral steroids (\>=20 mg/day prednisone or equivalent), or aspirin (\> 325 mg/day).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | Baseline and Week 8 | Healing at Week 4 or 8 were based on improvement of eGERD of the Los Angeles (LA) classification of esophagitis Grade A or B from Baseline. Classifications include: Not Present: No breaks (erosions) in the esophageal 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. Gread D: Mucosal breaks involving at least 75% of the esophageal circumference. |
| Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | Baseline and Week 4 | Healing at Week 4 or 8 were based on improvement of eGERD of the LA classification of esophagitis Grade A or B from Baseline. Classifications include: Not Present: No breaks (erosions) in the esophageal 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. Gread D: Mucosal breaks involving at least 75% of the esophageal circumference. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | Week 4 | During the first 4 weeks of the Double-blind Phase, participants were to record heartburn in a daily diary. Participant daily symptoms for the assessment of heartburn was based on a commonly used 4-point Likert scale of none, mild, moderate and severe. A participant was considered achieving sustained resolution of heartburn if the participant had maintained at least 7 consecutive heartburn-free days. |
Countries
United States
Participant flow
Pre-assignment details
Out of 1397 participants who were randomized, 1380 participants received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| ESO 40 mg ESO 40 mg capsule concurrently with placebo (identical in appearance to the RAB ER 50 mg capsule), once daily for 4 to 8 weeks. | 681 |
| RAB ER 50 mg RAB ER 50 mg capsule concurrently with placebo (identical in appearance to the ESO 40 mg capsule), once daily for 4 to 8 weeks. | 697 |
| Total | 1,378 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 11 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 25 | 23 |
| Overall Study | Other | 7 | 8 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 7 |
| Overall Study | Withdrawal of consent | 8 | 14 |
Baseline characteristics
| Characteristic | ESO 40 mg | RAB ER 50 mg | Total |
|---|---|---|---|
| Age, Continuous | 46.6 Years STANDARD_DEVIATION 13.16 | 47 Years STANDARD_DEVIATION 13.02 | 46.8 Years STANDARD_DEVIATION 13.08 |
| Sex: Female, Male Female | 351 Participants | 379 Participants | 730 Participants |
| Sex: Female, Male Male | 330 Participants | 318 Participants | 648 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 676 | 0 / 685 |
| serious Total, serious adverse events | 6 / 676 | 3 / 685 |
Outcome results
Primary
Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks
Healing at Week 4 or 8 were based on improvement of eGERD of the LA classification of esophagitis Grade A or B from Baseline. Classifications include: Not Present: No breaks (erosions) in the esophageal 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. Gread D: Mucosal breaks involving at least 75% of the esophageal circumference.
Time frame: Baseline and Week 4
Population: The analysis was performed using the ITT population, defined as all randomized subjects who received at least 1 dose of study drug, minus two participants from one site who were excluded from the ITT Population per an agreement with the FDA due to concerns of possible misconduct.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESO 40 mg | Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | Yes | 75.3 Percentage of Participants |
| ESO 40 mg | Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | No | 21 Percentage of Participants |
| ESO 40 mg | Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | Missing | 3.7 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | Yes | 75.9 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | No | 19.1 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks | Missing | 5 Percentage of Participants |
Primary
Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks
Healing at Week 4 or 8 were based on improvement of eGERD of the Los Angeles (LA) classification of esophagitis Grade A or B from Baseline. Classifications include: Not Present: No breaks (erosions) in the esophageal 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. Gread D: Mucosal breaks involving at least 75% of the esophageal circumference.
Time frame: Baseline and Week 8
Population: The analysis was performed using the Intent-to-Treat (ITT) population, defined as all randomized subjects who received at least 1 dose of study drug, minus two participants from one site who were excluded from the ITT Population per an agreement with the FDA due to concerns of possible misconduct.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESO 40 mg | Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | Yes | 87.8 Percentage of Participants |
| ESO 40 mg | Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | No | 6.3 Percentage of Participants |
| ESO 40 mg | Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | Missing | 5.9 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | Yes | 88.2 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | No | 5.9 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks | Missing | 5.9 Percentage of Participants |
Secondary
Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4
During the first 4 weeks of the Double-blind Phase, participants were to record heartburn in a daily diary. Participant daily symptoms for the assessment of heartburn was based on a commonly used 4-point Likert scale of none, mild, moderate and severe. A participant was considered achieving sustained resolution of heartburn if the participant had maintained at least 7 consecutive heartburn-free days.
Time frame: Week 4
Population: The analysis was performed using the ITT population, defined as all randomized subjects who received at least 1 dose of study drug, minus two participants from one site who were excluded from the ITT Population per an agreement with the FDA due to concerns of possible misconduct.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESO 40 mg | Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | Yes | 38.5 Percentage of Participants |
| ESO 40 mg | Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | No | 50.8 Percentage of Participants |
| ESO 40 mg | Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | Missing | 10.7 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | Yes | 41.9 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | No | 47.1 Percentage of Participants |
| RAB ER 50 mg | Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 | Missing | 11 Percentage of Participants |