A Phase 3 interventional study of Rabeprazole and Rabeprazole in Gastroesophageal Reflux Disease, sponsored by Eisai Co., Ltd.. Completed at 61 sites in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2023-06-22.
Sponsored by Eisai Co., Ltd. · Phase 3, Interventional, and Treatment
The purpose of this study is to assess the efficacy and safety of rabeprazole 10mg once and twice daily in maintenance therapy for PPI resistant gastroesophageal reflux disease patients.
This is randomized, multicenter, parallel-group, double-blind trial that investigates the efficacy and safety of rabeprazole 10mg twice daily over a period of 52 weeks. The 8-week Treatment Period (unblinded) was followed by a 52-week Maintenance Period (blinded). Participants with cure (modified Los Angeles Classification Grade N or Grade M) at the final endoscopy of the Treatment Period were entered into the Maintenance Period. Participants without cure were discontinued from the study. The participants in the Treatment Period were randomized to take Arm C or Arm D at a ratio of 1:1. The non-recurrence rate as endoscopically confirmed at 52 weeks shall be the primary end point, and this shall be examined through a randomized, multicenter, parallel-group, double-blind trial that investigates the efficacy and safety of rabeprazole 10mg twice daily over a period of 52 weeks.
1,067 studies on the registry are indexed under Gastroesophageal Reflux; 188 are open to participants now.
This study's enrollment of 517 is above the median of 72 across 712 interventional studies indexed under Gastroesophageal Reflux.
Browse Gastroesophageal Reflux studies →Eisai Co., Ltd. is the lead sponsor of 149 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Subjects fulfilling all of the below criteria shall be eligible for the study:
Exclusion Criteria:
Subjects fulfilling any of the following criteria shall be excluded from the study:
Drug: Rabeprazole
Drug: Rabeprazole
Drug: Rabeprazole
Drug: Rabeprazole
Rabeprazole 10 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Also known as: E3810
Rabeprazole 20 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Also known as: E3810
Rabeprazole 10 mg or 20 mg were administered orally twice daily during the treatment period (unblinded), and 10 mg was administered once daily during the maintenance period (double-blind).
Also known as: E3810
Rabeprazole 10 or 20 mg were administered orally twice daily during the treatment period (unblinded), and 10 mg was administered twice daily during the maintenance period (double-blind).
Also known as: E3810
Rate of Non-recurrence at Week 52
The non-recurrence rate (at 52 weeks) was determined by the endoscopy central review panel who were blinded to the investigator's assessment, based on the modified Los Angeles Classification using endoscopy photos were submitted by each of the institutions. Participants showing Grade A or above based on the modified Los Angeles Classification were included as a recurrence.
Time frame: Week 52
Rate of Non-recurrence at Weeks 12 and 24
The non-recurrence rate (up to 52 weeks) was determined by the endoscopy central review panel who were blinded to the investigator's assessment, based on the modified Los Angeles Classification using endoscopy photos were submitted by each of the institutions. Participants showing Grade A or above based on the modified Los Angeles Classification were included as a recurrence. The 95% CI was calculated by normal approximation.
Time frame: Weeks 12 and 24
Cumulative Non-recurrence Rate at Week 52
Non-recurrence rate at Week 52 was estimated using the Kaplan-Meier method.
Time frame: Week 52
Percentage of Participants With Heartburn (Daytime / Nighttime) During the Maintenance Therapy Period
A comparison of the rabeprazole 10 mg once daily group and the rabeprazole 10 mg twice daily group was performed for participants who did not exhibit daytime or nighttime heartburn at Week 0 of the Maintenance Therapy Period. Heartburn is a burning sensation in the stomach or lower chest; it is worsened by bending or pressure on the abdomen. Heartburn frequency was rated from 0-day (no) to 7-day (always) and severity was graded on a 3-point scale (mild, moderate, severe). Heartburn was evaluated in the daytime (from wake-up time to time for bed) and nighttime (from time for bed to wake-up time).
Time frame: From Week 4 up to Week 52
Frequency of Heartburn (Daytime / Nighttime) During the Maintenance Therapy Period
A comparison of rabeprazole 10 mg once daily group and the rabeprazole 10 mg twice daily group shall be performed for participants who did not exhibit daytime or nighttime heartburn at 0 weeks of the maintenance therapy period. Daytime and nighttime heartburn, and nighttime sleep disorders shall likewise be compared. For the participants who had recurrence, values at the final evaluation were imputed using a last observation carried forward (LOCF) method.
Time frame: From Week 4 up to Week 52
Severity of Heartburn (Daytime / Nighttime) During the Maintenance Therapy Period
A comparison of the rabeprazole (10 mg once daily group) and the rabeprazole (10 mg twice daily group) was performed for participants who did not exhibit daytime or nighttime heartburn at Week 0 of the Maintenance Therapy Period. The presence or absence of heartburn was assessed by the investigators during medical interviews. The heartburn incidence during each of the 7-day periods immediately before visiting the hospital was assessed on a scale of five stages based on the number of days with symptoms: 0 (no symptoms), 1 to 2 (occasional symptoms), 3 to 4 (sometimes had symptoms), 5 to 6 (often had symptoms), and 7 (always had symptoms). The incidence was tabulated by an analysis classifying the states into two groups: "no symptom group" (0 days with symptoms) and "with symptoms group" (1 day or more with symptoms). The severity of heartburn was as below: Mild (feel heartburn but tolerable), Moderate (feel heartburn and hard), and Severe (feel heartburn and terrible).
Time frame: From Week 4 up to Week 52
Percentage of Participants With Sleep Disorders During the Maintenance Therapy Period
Sleep disorders were defined as the condition of lack of dead sleep and arousal during sleep arising from heartburn or acid reflux. Sleep disorders during each of the 7-day periods immediately before visiting the hospital were assessed. Evaluation of sleep disorders arising from heartburn or acid reflux included recording if sleep-inducing drugs were being taken before enrollment; their type, method of use, and dosage. It was requested that no changes in sleep-inducing drug be made after enrollment. Sleep disorders were rated from 0-day (no) to 7-day (always). The incidence of sleep disorder was tabulated by an analysis classifying the stages into two groups: "No" (0 days with sleep disorder) and "Yes" (1 or more days with sleep disorder). Heartburn was evaluated prior to 7 days of each visit.
Time frame: From Week 4 up to Week 52
Frequency of Sleep Disorders During the Maintenance Therapy Period
Sleep disorders were defined as the condition of lack of dead sleep and arousal during sleep arising from heartburn or acid reflux. Evaluation of sleep disorders arising from heartburn or acid reflux included recording if sleep-inducing drugs were being taken before enrollment; their type, method of use, and dosage. It was requested that no changes in sleep-inducing drug be made after enrollment. Sleep disorders were rated from 0-day (no) to 7-day (always). Heartburn was evaluated prior to 7 days of each visit.
Time frame: From Week 4 up to Week 52
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Safety was assessed by monitoring and recording all adverse events (AEs) and SAEs, regular monitoring of hematology, clinical chemistry, urine values, and regular measurement of vital signs. All AEs were graded on a 3-point scale; 1) mild was defined as discomfort that did not interfere with normal daily activities, 2) moderate was defined as discomfort that interfered with normal activities, and 3) severe was defined as discomfort that interfered with the ability to work or normal daily activities were impossible. SAEs were medical events that led to death, were life-threatening, required hospitalization or prolongation of hospitalization, caused persistent disability, or resulted in a congenital abnormality. TEAEs were AEs with an onset date on or after the first dose of study drug and up to 30 days after receiving the last dose of study drug. Treatment-related AEs were medical events that were considered by the investigator to be possibly or probably related to rabeprazole.
Time frame: From date of first dose up to 30 days after the last dose of study drug, up to approximately 1 year 3 months (Treatment Period; 8 weeks, Maintenance Therapy Period; 52 weeks, and Follow-up Period; 30 days)
| Milestone | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|---|---|
| Started | 437 | 80 | 0 | 0 |
| Completed | 305 | 54 | 0 | 0 |
| Not completed | 132 | 26 | 0 | 0 |
| Withdrew: Withdrawal by subject | 11 | 0 | 0 | 0 |
| Withdrew: Adverse event | 5 | 2 | 0 | 0 |
| Withdrew: Pregnancy | 1 | 0 | 0 | 0 |
| Withdrew: Other | 115 | 24 | 0 | 0 |
| Milestone | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|---|---|
| Started | 0 | 0 | 178 | 181 |
| Completed | 0 | 0 | 163 | 161 |
| Not completed | 0 | 0 | 15 | 20 |
| Withdrew: Adverse event | 0 | 0 | 3 | 7 |
| Withdrew: Withdrawal by subject | 0 | 0 | 5 | 4 |
| Withdrew: Pregnancy | 0 | 0 | 0 | 1 |
| Withdrew: Other | 0 | 0 | 7 | 8 |
The non-recurrence rate (at 52 weeks) was determined by the endoscopy central review panel who were blinded to the investigator's assessment, based on the modified Los Angeles Classification using endoscopy photos were submitted by each of the institutions. Participants showing Grade A or above based on the modified Los Angeles Classification were included as a recurrence.
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| Non-recurrence | 44.8 (37.2 to 52.4) | 73.9 (67.1 to 80.7) |
| Recurrence | 55.2 (NA to NA) | 26.1 (NA to NA) |
The non-recurrence rate (up to 52 weeks) was determined by the endoscopy central review panel who were blinded to the investigator's assessment, based on the modified Los Angeles Classification using endoscopy photos were submitted by each of the institutions. Participants showing Grade A or above based on the modified Los Angeles Classification were included as a recurrence. The 95% CI was calculated by normal approximation.
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| Week 12, Non-recurrence | 62.5 (55.2 to 69.8) | 92.4 (88.4 to 96.4) |
| Week 12, Recurrence | 37.5 (NA to NA) | 7.6 (NA to NA) |
| Week 24, Non-recurrence | 55.8 (48.2 to 63.3) | 85.1 (79.7 to 90.5) |
| Week 24, Recurrence | 44.2 (NA to NA) | 14.9 (NA to NA) |
Non-recurrence rate at Week 52 was estimated using the Kaplan-Meier method.
| Percentage of non-recurrence | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| Cumulative Non-recurrence Rate at Week 52 | 41.5 (33.0 to 49.8) | 71.4 (62.8 to 78.4) |
A comparison of the rabeprazole 10 mg once daily group and the rabeprazole 10 mg twice daily group was performed for participants who did not exhibit daytime or nighttime heartburn at Week 0 of the Maintenance Therapy Period. Heartburn is a burning sensation in the stomach or lower chest; it is worsened by bending or pressure on the abdomen. Heartburn frequency was rated from 0-day (no) to 7-day (always) and severity was graded on a 3-point scale (mild, moderate, severe). Heartburn was evaluated in the daytime (from wake-up time to time for bed) and nighttime (from time for bed to wake-up time).
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| Heartburn (yes) | 23.2 | 8.0 |
| Heartburn (no) | 76.8 | 92.0 |
A comparison of rabeprazole 10 mg once daily group and the rabeprazole 10 mg twice daily group shall be performed for participants who did not exhibit daytime or nighttime heartburn at 0 weeks of the maintenance therapy period. Daytime and nighttime heartburn, and nighttime sleep disorders shall likewise be compared. For the participants who had recurrence, values at the final evaluation were imputed using a last observation carried forward (LOCF) method.
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| 0 Days (no symptoms) | 85.2 | 85.1 |
| 1 to 2 Days (occasional symptoms) | 12.3 | 11.2 |
| 3 to 4 Days (sometimes had symptoms) | 1.9 | 0.6 |
| 5 to 6 Days (often had symptoms) | 0.0 | 1.9 |
| 7 Days (always had symptoms) | 0.6 | 1.2 |
A comparison of the rabeprazole (10 mg once daily group) and the rabeprazole (10 mg twice daily group) was performed for participants who did not exhibit daytime or nighttime heartburn at Week 0 of the Maintenance Therapy Period. The presence or absence of heartburn was assessed by the investigators during medical interviews. The heartburn incidence during each of the 7-day periods immediately before visiting the hospital was assessed on a scale of five stages based on the number of days with symptoms: 0 (no symptoms), 1 to 2 (occasional symptoms), 3 to 4 (sometimes had symptoms), 5 to 6 (often had symptoms), and 7 (always had symptoms). The incidence was tabulated by an analysis classifying the states into two groups: "no symptom group" (0 days with symptoms) and "with symptoms group" (1 day or more with symptoms). The severity of heartburn was as below: Mild (feel heartburn but tolerable), Moderate (feel heartburn and hard), and Severe (feel heartburn and terrible).
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| None | 85.2 | 85.1 |
| Mild | 14.8 | 14.3 |
| Moderate | 0.0 | 0.6 |
| Severe | 0.0 | 0.0 |
Sleep disorders were defined as the condition of lack of dead sleep and arousal during sleep arising from heartburn or acid reflux. Sleep disorders during each of the 7-day periods immediately before visiting the hospital were assessed. Evaluation of sleep disorders arising from heartburn or acid reflux included recording if sleep-inducing drugs were being taken before enrollment; their type, method of use, and dosage. It was requested that no changes in sleep-inducing drug be made after enrollment. Sleep disorders were rated from 0-day (no) to 7-day (always). The incidence of sleep disorder was tabulated by an analysis classifying the stages into two groups: "No" (0 days with sleep disorder) and "Yes" (1 or more days with sleep disorder). Heartburn was evaluated prior to 7 days of each visit.
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| Sleep disorders from heartburn/acid reflux (yes) | 2.5 | 2.5 |
| Sleep disorders from heartburn/acid reflux (no) | 97.5 | 97.5 |
Sleep disorders were defined as the condition of lack of dead sleep and arousal during sleep arising from heartburn or acid reflux. Evaluation of sleep disorders arising from heartburn or acid reflux included recording if sleep-inducing drugs were being taken before enrollment; their type, method of use, and dosage. It was requested that no changes in sleep-inducing drug be made after enrollment. Sleep disorders were rated from 0-day (no) to 7-day (always). Heartburn was evaluated prior to 7 days of each visit.
| Percentage of participants | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|
| 0 Day (none) | 96.9 | 98.1 |
| 1 to 2 Days (occasional symptoms) | 2.5 | 0.6 |
| 3 to 4 Days (sometimes had symptoms) | 0.6 | 0.0 |
| 5 to 6 Days (often had symptoms) | 0.0 | 0.6 |
| 7 Days (always had symptoms) | 0.0 | 0.6 |
Safety was assessed by monitoring and recording all adverse events (AEs) and SAEs, regular monitoring of hematology, clinical chemistry, urine values, and regular measurement of vital signs. All AEs were graded on a 3-point scale; 1) mild was defined as discomfort that did not interfere with normal daily activities, 2) moderate was defined as discomfort that interfered with normal activities, and 3) severe was defined as discomfort that interfered with the ability to work or normal daily activities were impossible. SAEs were medical events that led to death, were life-threatening, required hospitalization or prolongation of hospitalization, caused persistent disability, or resulted in a congenital abnormality. TEAEs were AEs with an onset date on or after the first dose of study drug and up to 30 days after receiving the last dose of study drug. Treatment-related AEs were medical events that were considered by the investigator to be possibly or probably related to rabeprazole.
| Participants | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once daiArm C | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|---|---|
| TEAEs | 111 | 21 | 111 | 125 |
| Treatment-related TEAEs | 20 | 1 | 7 | 11 |
| Severe TEAEs | 2 | 1 | 4 | 3 |
| Serious TEAEs | 6 | 4 | 11 | 17 |
Collected over From date of first dose up to 30 days after the last dose of study drug, up to approximately 1 year 3 months (Treatment Period; 8 weeks, Maintenance Therapy Period; 52 weeks, and Follow-up Period; 30 days). Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Rabeprazole: 10 mg Twice Daily | 0/437 (0%) | 6/437 (1.4%) | 63/437 (14.4%) |
| Rabeprazole: 20 mg Twice Daily | 0/80 (0%) | 4/80 (5%) | 12/80 (15%) |
| Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | 1/178 (0.6%) | 11/178 (6.2%) | 75/178 (42.1%) |
| Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily | 0/181 (0%) | 17/181 (9.4%) | 87/181 (48.1%) |
| Event | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|---|---|
| Diverticulum intestinal haemorrhagicGastrointestinal disorders | 0/437 | 1/80 | 0/178 | 0/181 |
| Femoral neck fractureInjury, poisoning and procedural complications | 0/437 | 1/80 | 0/178 | 0/181 |
| Small intestine carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/437 | 1/80 | 0/178 | 0/181 |
| Pneumonia aspirationRespiratory, thoracic and mediastinal disorders | 0/437 | 1/80 | 0/178 | 0/181 |
| Inguinal herniaGastrointestinal disorders | 0/437 | 0/80 | 1/178 | 1/181 |
| Oesophageal ulcerGastrointestinal disorders | 0/437 | 0/80 | 1/178 | 0/181 |
| Large intestine polypGastrointestinal disorders | 0/437 | 0/80 | 1/178 | 0/181 |
| DrowningGeneral disorders | 0/437 | 0/80 | 1/178 | 0/181 |
| SepsisInfections and infestations | 0/437 | 0/80 | 1/178 | 0/181 |
| Infectious pleural effusionInfections and infestations | 0/437 | 0/80 | 1/178 | 0/181 |
| Event | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily | Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily |
|---|---|---|---|---|
| NasopharyngitisInfections and infestations | 25/437 | 5/80 | 32/178 | 33/181 |
| DiarrhoeaGastrointestinal disorders | 4/437 | 0/80 | 3/178 | 10/181 |
| Upper respiratory tract infectionInfections and infestations | 3/437 | 2/80 | 9/178 | 10/181 |
| Back painMusculoskeletal and connective tissue disorders | 6/437 | 0/80 | 4/178 | 9/181 |
| PharyngitisInfections and infestations | 4/437 | 0/80 | 5/178 | 8/181 |
| EczemaSkin and subcutaneous tissue disorders | 1/437 | 0/80 | 6/178 | 8/181 |
| Dental cariesGastrointestinal disorders | 0/437 | 1/80 | 7/178 | 3/181 |
| Abdominal pain upperGastrointestinal disorders | 1/437 | 0/80 | 3/178 | 6/181 |
| ContusionInjury, poisoning and procedural complications | 3/437 | 0/80 | 4/178 | 6/181 |
| InfluenzaInfections and infestations | 2/437 | 0/80 | 5/178 | 4/181 |
| Age, Continuous(Years) | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Total |
|---|---|---|---|
| Mean | 64.0 ± 13.1 | 70.2 ± 12.7 | 64.6 ± 13.6 |
| Sex/Gender, Customized(Participants) | Rabeprazole: 10 mg Twice Daily | Rabeprazole: 20 mg Twice Daily | Total |
|---|---|---|---|
| Male | 282 | 31 | 313 |
| Female | 155 | 49 | 204 |
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Eisai Co., Ltd.