Maintenance Intermittent Therapy for Symptomatic GERD Patients
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: Rabeprazole 20 mg
rabeprazole sodium tablet 20 mg once daily
Other Names:
|
| Experimental: Rabeprazole 20 mg
|
Drug: Rabeprazole 20 mg
rabeprazole sodium tablet 20 mg once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Male or female patients, 18 to 65 years of age.
-
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.
-
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.
-
Patients must have at least 4 days with heartburn per week in each of the 2 weeks prior to Screening.
-
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:
-
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.
-
Females must not be pregnant, lactating or have a positive urine eta human chorionic gonadotropin (B-hCG) laboratory result.
-
Patients with a history of allergy or sensitivity to proton pump inhibitors or to their inactive ingredients.
-
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).
-
Patients who have a history of Barrett's esophagus, esophageal stricture, or pyloric stenosis.
-
Patients with a history of endoscopically-proven esophagitis any time in the past.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Quality Care Medical Center Inc. | Vista | California | United States | 92085 |
Sponsors and Collaborators
- Eisai Inc.
Investigators
- Study Director: Yufang Lu, Eisai Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E3810-A001-203
Study Results
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 Detail | 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). |
| Arm/Group Title | Rabeprazole 20 mg | Placebo |
|---|---|---|
| Arm/Group Description | Orally, once daily for 7- to 14-day courses intermittently during the 6-month Double-blind Maintenance Treatment Phase. | Orally, once daily for 7- to 14-day courses intermittently during the 6-month Double-blind Maintenance Treatment Phase. |
| Period Title: Overall Study | ||
| STARTED | 103 | 97 |
| COMPLETED | 73 | 35 |
| NOT COMPLETED | 30 | 62 |
Baseline Characteristics
| Arm/Group Title | Rabeprazole 20 mg | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Orally, once daily for 7 to 14-day courses intermittently during the 6-month Maintenance Treatment Phase (ITT population). | Orally, once daily for 7 to 14-day courses intermittently during the 6-month Maintenance Treatment Phase (ITT population). | Total of all reporting groups |
| Overall Participants | 96 | 91 | 187 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
46.0
(11.67)
|
46.6
(11.69)
|
46.3
(11.66)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
64
66.7%
|
59
64.8%
|
123
65.8%
|
| Male |
32
33.3%
|
32
35.2%
|
64
34.2%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
1.1%
|
1
0.5%
|
| Asian |
1
1%
|
0
0%
|
1
0.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
9
9.4%
|
10
11%
|
19
10.2%
|
| White |
74
77.1%
|
64
70.3%
|
138
73.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
12
12.5%
|
16
17.6%
|
28
15%
|
Outcome Measures
| Title | The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population). |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Rabeprazole 20 mg | Placebo |
|---|---|---|
| Arm/Group Description | Orally, once daily for 7 to 14-day courses intermittently during the 6-month Maintenance Treatment Phase (ITT population). | Orally, once daily for 7 to 14-day courses intermittently during the 6-month Maintenance Treatment Phase (ITT population). |
| Measure Participants | 96 | 91 |
| Mean (Standard Deviation) [Percentage of Days] |
82.58
(14.39)
|
62.17
(29.93)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Rabeprazole 20 mg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | p-value was adjusted for multiple comparisons. | |
| Method | t-test, 2 sided | |
| Comments | The primary analysis was on the ITT population using all observed data collected from Day 1 of the maintenance phase until the endpoint. | |
| Title | The Percent of Heartburn-free Daytime Period During the 6-month Maintenance Treatment Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | The Percent of Heartburn-free Nighttime Period During the 6-month Maintenance Treatment Phase |
|---|---|
| Description | The percentage of heartburn-free nighttime period is presented cumulatively including all data collected during the 6-month |
| Time Frame | 6-month maintenance phase |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 6 month maintenance phase | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population (total 200 subjects) was used for safety analysis and participant flow. | |||
| Arm/Group Title | Rabeprazole 20 mg | Placebo | ||
| Arm/Group Description | Orally, once daily for 7- to 14-day courses intermittently during the 6-month Double-blind Maintenance Treatment Phase. | Orally, once daily for 7- to 14-day courses intermittently during the 6-month Double-blind Maintenance Treatment Phase. | ||
All Cause Mortality |
||||
| Rabeprazole 20 mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Rabeprazole 20 mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/ (NaN) | 2/ (NaN) | ||
| Gastrointestinal disorders | ||||
| Gallstone pancreatitis | 0/103 (0%) | 0 | 1/97 (1%) | 1 |
| General disorders | ||||
| Chest pain | 1/103 (1%) | 1 | 0/97 (0%) | 0 |
| Infections and infestations | ||||
| Pneumonia | 0/103 (0%) | 0 | 1/97 (1%) | 1 |
| Nervous system disorders | ||||
| Schizoaffective disorder/depression | 1/103 (1%) | 1 | 0/97 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Rabeprazole 20 mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/ (NaN) | 36/ (NaN) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 7/103 (6.8%) | 1/97 (1%) | ||
| Erosive gastritis | 2/103 (1.9%) | 4/97 (4.1%) | ||
| Hiatus hernia | 6/103 (5.8%) | 4/97 (4.1%) | ||
| Nausea | 5/103 (4.9%) | 3/97 (3.1%) | ||
| Esophageal erosion | 2/103 (1.9%) | 6/97 (6.2%) | ||
| Esophagitis | 4/103 (3.9%) | 5/97 (5.2%) | ||
| Infections and infestations | ||||
| Viral gastroenteritis | 0/103 (0%) | 4/97 (4.1%) | ||
| Sinusitis | 2/103 (1.9%) | 4/97 (4.1%) | ||
| Nervous system disorders | ||||
| Headache | 5/103 (4.9%) | 3/97 (3.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/103 (4.9%) | 2/97 (2.1%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Yufang Lu, Study Director |
|---|---|
| Organization | Eisai Medical Research Inc. |
| Phone | 201-403-2500 |
- E3810-A001-203