A Double-blind Comparative Study of the Efficacy and Safety of E3810 10mg Once and Twice Daily in Maintenance Therapy for PPI Resistant Gastroesophageal Reflux Disease Patients

June 16, 2023 updated by: Eisai Co., Ltd.
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
517

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Akita, Japan
      • Fukuoka, Japan
      • Hiroshima, Japan
      • Kochi, Japan
      • Kyoto, Japan
      • Nagasaki, Japan
      • Oita, Japan
      • Osaka, Japan
      • Saga, Japan
      • Saitama, Japan
      • Yamagata, Japan
    • Aichi
      • Nagoya, Aichi, Japan
    • Chiba
      • Inzai, Chiba, Japan
      • Kamagaya, Chiba, Japan
    • Ehime
      • Matsuyama, Ehime, Japan
    • Fukuoka
      • Kitakyushu, Fukuoka, Japan
      • Onga, Fukuoka, Japan
    • Fukushima
      • Koriyama, Fukushima, Japan
    • Gunma
      • Annaka, Gunma, Japan
    • Hiroshima
      • Fukuyama, Hiroshima, Japan
    • Hokkaido
      • Asahikawa, Hokkaido, Japan
      • Ishikari, Hokkaido, Japan
      • Sapporo, Hokkaido, Japan
    • Hyogo
      • Amagasaki, Hyogo, Japan
      • Kobe, Hyogo, Japan
      • Nishinomiya, Hyogo, Japan
    • Ibaraki
      • Furukawa, Ibaraki, Japan
      • Tsuchiura, Ibaraki, Japan
    • Kagawa
      • Takamatsu, Kagawa, Japan
    • Kagoshima
      • Ichikikushikino-shi, Kagoshima, Japan
    • Kanagawa
      • Kamakura, Kanagawa, Japan
      • Kawasaki, Kanagawa, Japan
      • Yokohama, Kanagawa, Japan
    • Miyagi
      • Sendai, Miyagi, Japan
    • Nagano
      • Suwa, Nagano, Japan
    • Oita
      • Beppu, Oita, Japan
    • Osaka
      • Fujiidera, Osaka, Japan
      • Hirakata, Osaka, Japan
      • Kishiwada, Osaka, Japan
      • Takatsuki, Osaka, Japan
    • Saga
      • Karatsu, Saga, Japan
      • Ureshino, Saga, Japan
    • Saitama
      • Ageo, Saitama, Japan
      • Hiki, Saitama, Japan
      • Toda, Saitama, Japan
      • Wako, Saitama, Japan
    • Shimane
      • Izumo, Shimane, Japan
    • Shizuoka
      • Fujieda, Shizuoka, Japan
      • Hamamatsu, Shizuoka, Japan
    • Tochigi
      • Ōtawara, Tochigi, Japan
    • Tokyo
      • Adachi, Tokyo, Japan
      • Bunkyo, Tokyo, Japan
      • Chuo, Tokyo, Japan
      • Koto, Tokyo, Japan
      • Minato, Tokyo, Japan
      • Nerima, Tokyo, Japan
      • Ota, Tokyo, Japan
      • Setagaya, Tokyo, Japan
      • Shibuya, Tokyo, Japan
      • Shinagawa, Tokyo, Japan
      • Toshima, Tokyo, Japan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects fulfilling all of the below criteria shall be eligible for the study:

  1. Patients diagnosed with gastroesophageal reflux disease who are shown through endoscopic examination to have mucosal lesions (erosions, ulcers)
  2. Patients shown through endoscopy not to have recovered despite administration of PPI once daily for eight weeks.
  3. Patients over 20 years of age who have freely given their informed consent in writing to participation in the study.
  4. Patients who, having received a full explanation of the matters that must be adhered to during the study, intend to adhere to their requirements, and are capable of doing so.

Exclusion Criteria:

Subjects fulfilling any of the following criteria shall be excluded from the study:

  1. Patients considered candidates for surgical treatment of the upper gastrointestinal tract due to perforation, esophageal stricture, pyloric stenosis, esophageal varices, etc.
  2. Patients with Zollinger-Ellison syndrome.
  3. Patients with gastrointestinal hemorrhage.
  4. Patients with serious cardiovascular disease, cerebrovascular disease, hematological disorders, renal disease, liver disease, malignant tumors, etc.
  5. Patients with long segment Barrett's esophagus.
  6. Patients with open gastric or duodenal ulcers.
  7. Patients with drug allergies or a past history of drug allergies to PPI.
  8. Patients who are taking other drugs under development, or have done so within 12 weeks prior to enrollment.
  9. Patients who are, or may be pregnant, patients who wish to become pregnant during the study period, patients who are breastfeeding, and patients or their partners who do not wish to use reliable contraceptive measures.
  10. Patients with a history of dependence on or abuse of drugs or alcohol within the past two years.
  11. Other patients deemed unsuitable for inclusion in the study by the principal investigator or sub-investigators.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A
Drug: Rabeprazole
Rabeprazole 10 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
Rabeprazole 20 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Experimental: Arm B
Drug: Rabeprazole
Rabeprazole 10 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
Rabeprazole 20 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Experimental: Arm C
Drug: Rabeprazole
Rabeprazole 10 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
Rabeprazole 20 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Experimental: Arm D
Drug: Rabeprazole
Rabeprazole 10 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
Rabeprazole 20 mg was administered orally twice daily during the treatment period for 8 weeks (unblinded).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810
Drug: Rabeprazole
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).
Other Names:
  • E3810

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of Non-recurrence at Week 52
Time Frame: 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.
Week 52

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of Non-recurrence at Weeks 12 and 24
Time Frame: 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.
Weeks 12 and 24
Cumulative Non-recurrence Rate at Week 52
Time Frame: Week 52
Non-recurrence rate at Week 52 was estimated using the Kaplan-Meier method.
Week 52
Percentage of Participants With Heartburn (Daytime / Nighttime) During the Maintenance Therapy Period
Time Frame: From Week 4 up to Week 52
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).
From Week 4 up to Week 52
Frequency of Heartburn (Daytime / Nighttime) During the Maintenance Therapy Period
Time Frame: From Week 4 up to Week 52
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.
From Week 4 up to Week 52
Severity of Heartburn (Daytime / Nighttime) During the Maintenance Therapy Period
Time Frame: From Week 4 up to Week 52
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).
From Week 4 up to Week 52
Percentage of Participants With Sleep Disorders During the Maintenance Therapy Period
Time Frame: From Week 4 up to Week 52
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.
From Week 4 up to Week 52
Frequency of Sleep Disorders During the Maintenance Therapy Period
Time Frame: From Week 4 up to Week 52
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.
From Week 4 up to Week 52
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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)
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.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 9, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 16, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E3810-J081-311

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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