Trial Outcomes & Findings for Rabeprazole Extended-Release 50 mg Versus Esomeprazole 40 mg for Healing and Symptomatic Relief of Mild to Moderate Erosive Gastroesophageal Reflux Disease (GERD) (NCT NCT00658632)

Last Updated: 2016-05-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1397 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2016-05-04

Participant Flow

Out of 1397 participants who were randomized, 1380 participants received study treatment.

Participant milestones

Participant milestones
Measure	Esomeprazole (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.	Rabeprazole (RAB) Extended Release (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.
Overall Study STARTED	682	698
Overall Study COMPLETED	618	633
Overall Study NOT COMPLETED	64	65

Reasons for withdrawal

Reasons for withdrawal
Measure	Esomeprazole (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.	Rabeprazole (RAB) Extended Release (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.
Overall Study Adverse Event	13	11
Overall Study Lost to Follow-up	25	23
Overall Study Withdrawal by Subject	10	7
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal of consent	8	14
Overall Study Pregnancy	1	1
Overall Study Other	7	8

Baseline Characteristics

Rabeprazole Extended-Release 50 mg Versus Esomeprazole 40 mg for Healing and Symptomatic Relief of Mild to Moderate Erosive Gastroesophageal Reflux Disease (GERD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ESO 40 mg n=681 Participants ESO 40 mg capsule concurrently with placebo (identical in appearance to the RAB ER 50 mg capsule), once daily for 4 to 8 weeks.	RAB ER 50 mg n=697 Participants RAB ER 50 mg capsule concurrently with placebo (identical in appearance to the ESO 40 mg capsule), once daily for 4 to 8 weeks.	Total n=1378 Participants Total of all reporting groups
Age, Continuous	46.6 Years STANDARD_DEVIATION 13.16 • n=99 Participants	47 Years STANDARD_DEVIATION 13.02 • n=107 Participants	46.8 Years STANDARD_DEVIATION 13.08 • n=206 Participants
Sex: Female, Male Female	351 Participants n=99 Participants	379 Participants n=107 Participants	730 Participants n=206 Participants
Sex: Female, Male Male	330 Participants n=99 Participants	318 Participants n=107 Participants	648 Participants n=206 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	ESO 40 mg n=681 Participants ESO 40 mg capsule concurrently with placebo (identical in appearance to the RAB ER 50 mg capsule), once daily for 4 to 8 weeks.	RAB ER 50 mg n=697 Participants RAB ER 50 mg capsule concurrently with placebo (identical in appearance to the ESO 40 mg capsule), once daily for 4 to 8 weeks.
Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks Yes	87.8 Percentage of Participants	88.2 Percentage of Participants
Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks No	6.3 Percentage of Participants	5.9 Percentage of Participants
Percentage of Participants With Erosive Gastroesophageal Reflux Disease (eGERD) Who Achieved Endoscopically-confirmed Healing by 8 Weeks Missing	5.9 Percentage of Participants	5.9 Percentage of Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	ESO 40 mg n=681 Participants ESO 40 mg capsule concurrently with placebo (identical in appearance to the RAB ER 50 mg capsule), once daily for 4 to 8 weeks.	RAB ER 50 mg n=697 Participants RAB ER 50 mg capsule concurrently with placebo (identical in appearance to the ESO 40 mg capsule), once daily for 4 to 8 weeks.
Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks Yes	75.3 Percentage of Participants	75.9 Percentage of Participants
Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks No	21 Percentage of Participants	19.1 Percentage of Participants
Percentage of Participants With eGERD Who Achieved Endoscopically-confirmed Healing by 4 Weeks Missing	3.7 Percentage of Participants	5 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	ESO 40 mg n=681 Participants ESO 40 mg capsule concurrently with placebo (identical in appearance to the RAB ER 50 mg capsule), once daily for 4 to 8 weeks.	RAB ER 50 mg n=697 Participants RAB ER 50 mg capsule concurrently with placebo (identical in appearance to the ESO 40 mg capsule), once daily for 4 to 8 weeks.
Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 Yes	38.5 Percentage of Participants	41.9 Percentage of Participants
Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 No	50.8 Percentage of Participants	47.1 Percentage of Participants
Percentage of Participants Who Achieved Diary-recorded Sustained Resolution of Heartburn by Week 4 Missing	10.7 Percentage of Participants	11 Percentage of Participants

Adverse Events

ESO 40 mg

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

RAB ER 50 mg

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ESO 40 mg n=676 participants at risk ESO 40 mg capsule concurrently with placebo (identical in appearance to the RAB ER 50 mg capsule), once daily for 4 to 8 weeks.	RAB ER 50 mg n=685 participants at risk RAB ER 50 mg capsule concurrently with placebo (identical in appearance to the ESO 40 mg capsule), once daily for 4 to 8 weeks.
Cardiac disorders Acute coronary syndrome	0.00% 0/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.15% 1/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Cardiac disorders Acute myocardial infarction	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Gastrointestinal disorders Crohn's disease	0.00% 0/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.15% 1/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Infections and infestations Gastroenteritis	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.15% 1/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectosigmoid cancer	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Nervous system disorders Headache	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Renal and urinary disorders Renal failure acute	0.00% 0/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.15% 1/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Respiratory, thoracic and mediastinal disorders Asthma	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.15% 1/676 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.	0.00% 0/685 • For each participant, from the time of administration of the first dose of study drug up to 30 days after the administration of the last dose of study drug or up to resolution of adverse event or up to approximately 10 weeks. Data are presented as number of participants with treatment emergent adverse events. The analysis was performed using the Safety Analysis Set (SAS), defined as all subjects who received at least 1 dose of study drug and had a postbaseline safety assessment.

Other adverse events

Adverse event data not reported

Additional Information

Eisai Medical Services

Eisai Inc.

Phone: 888-422-4743

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place