Trial Outcomes & Findings for Rabeprazole Extended-Release 50 mg vs. Ranitidine 150 mg for Maintenance of Healed Erosive Gastroesophageal Reflux Disease (GERD) (NCT NCT00838526)

Last Updated: 2022-04-25

Results Overview

eGERD (erosive gastroesophageal reflux disease) healing measured by the Time-to-Relapse of Oesophageal Erosions using an Esophagogastroduodenoscopy (EGD). Lesions were identified and graded using the following Los Angeles (LA) classification of Oesophagitis: 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. Grade D: Mucosal breaks involving at least 75% of the esophageal circumference.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

240 participants

Primary outcome timeframe

Baseline to Week 26

Results posted on

2022-04-25

Participant Flow

Participants were eligible for this study if they had completed one of the healing studies (E3810-G000-301 or E3810-G000-303), had no evidence of oesophageal erosions, had sustained heartburn resolution, and had no record of any serious adverse event (SAE) related to study medication during the healing study.

Out of the 240 participants who were randomized in this study, 235 participants received study treatment.

Participant milestones

Participant milestones
Measure	RAN 150mg BID Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Overall Study STARTED	59	176
Overall Study COMPLETED	35	137
Overall Study NOT COMPLETED	24	39

Reasons for withdrawal

Reasons for withdrawal
Measure	RAN 150mg BID Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Overall Study Adverse Event	3	12
Overall Study Lost to Follow-up	4	12
Overall Study Withdrawal by Subject	4	5
Overall Study Lack of Efficacy	2	3
Overall Study Other	11	7

Baseline Characteristics

Rabeprazole Extended-Release 50 mg vs. Ranitidine 150 mg for Maintenance of Healed Erosive Gastroesophageal Reflux Disease (GERD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RAN 150mg BID n=59 Participants Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD n=176 Participants Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.	Total n=235 Participants Total of all reporting groups
Age, Customized	46.7 Years STANDARD_DEVIATION 12.15 • n=5 Participants	46.4 Years STANDARD_DEVIATION 12.83 • n=7 Participants	46.5 Years STANDARD_DEVIATION 12.64 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	81 Participants n=7 Participants	108 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	95 Participants n=7 Participants	127 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 26

Population: Intent-to-Treat (ITT) Population - all randomized subjects who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	RAN 150mg BID n=59 Participants Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD n=176 Participants Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Percentage of Participants With Maintenance of Complete Healing of eGERD at Week 26	32.9 Percentage of Participants	84.9 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: ITT

Heartburn or other GERD-associated symptoms (regurgitation, epigastric or chest pain, dysphagia, belching, bloating, early satiety, other) was based on a 4-point Likert scale that included the following: None (No symptoms); Mild (Awareness of symptoms but easily tolerated); Moderate (Discomforting symptom sufficient to cause interference with normal activities including sleep); Severe (Incapacitating symptom, inability to perform normal activities).

Outcome measures

Outcome measures
Measure	RAN 150mg BID n=59 Participants Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD n=176 Participants Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 Yes	8.5 Percentage of Participants	57.4 Percentage of Participants
Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 No	25.4 Percentage of Participants	18.8 Percentage of Participants
Percentage of Participants With Investigator-recorded Sustained Resolution of Heartburn at Week 26 Missing	66.1 Percentage of Participants	23.9 Percentage of Participants

SECONDARY outcome

Timeframe: From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks.

Population: The safety population included all randomized participants who received at least one dose of study drug and had at least one post-baseline safety assessment. Analyses of the safety population was based on the actual treatment participants received.

An adverse event (AE) was any untoward medical occurrence in a participant administered an investigational product. A treatment emergent AE (TEAE) was any AE beginning on or after the confirmed date of first dose of study medication, up to and including 7 days after the last dose of study medication. A TEAE was considered related to study treatment if a causal relationship between the study treatment and the AE was a reasonable possibility. AEs were graded as severe if they were incapacitating, with inability to work or to perform normal daily activity. Serious AEs (SAEs) were events that resulted in death, were life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or were a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	RAN 150mg BID n=59 Participants Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD n=173 Participants Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Percentage of Participants With Adverse Events by Category Treatment-related SAE	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Adverse Events by Category Any TEAE	47.5 Percentage of participants	64.2 Percentage of participants
Percentage of Participants With Adverse Events by Category Treatment-related TEAE	8.5 Percentage of participants	14.5 Percentage of participants
Percentage of Participants With Adverse Events by Category Severe TEAE	3.4 Percentage of participants	8.1 Percentage of participants
Percentage of Participants With Adverse Events by Category Severe, treatment-related TEAE	1.7 Percentage of participants	0.6 Percentage of participants
Percentage of Participants With Adverse Events by Category Death	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Adverse Events by Category Other SAE	1.7 Percentage of participants	6.4 Percentage of participants
Percentage of Participants With Adverse Events by Category TEAEs leading to discontinuation of treatment	6.8 Percentage of participants	6.9 Percentage of participants

Adverse Events

RAN 150mg BID

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

RAB ER 50mg QD

Serious events: 10 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	RAN 150mg BID n=59 participants at risk Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD n=173 participants at risk Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Gastrointestinal disorders Gastritis	1.7% 1/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	7.5% 13/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Infections and infestations Sinusitis	1.7% 1/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	6.4% 11/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Gastrointestinal disorders Hiatus hernia	3.4% 2/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	5.8% 10/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Gastrointestinal disorders Nausea	6.8% 4/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	5.2% 9/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.

Additional Information

Eisai Medical Information, Eisai

Eisai Inc.

Phone: +1 888 274 2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	RAN 150mg BID n=59 participants at risk Morning dose included 1 x Placebo to match RAB (Rabeprazole) ER (Extended Release) 50mg capsule and 1 x RAN (Ranitidine) 150mg capsule. Evening dose included 1 x RAN 150mg capsule. Received study drug orally daily for 26 weeks.	RAB ER 50mg QD n=173 participants at risk Morning dose included 1 x RAB ER 50mg capsule and 1 x Placebo to match RAN 150mg capsule. Evening dose included 1 x Placebo to match RAN 150mg capsule. Received study drug orally daily for 26 weeks.
Cardiac disorders Angina pectoris	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Cardiac disorders Intracardiac thrombus	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Gastrointestinal disorders Abdominal hernia	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Gastrointestinal disorders Abdominal mass	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Gastrointestinal disorders Abdominal pain	1.7% 1/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.00% 0/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
General disorders Fatigue	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	1.2% 2/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Hepatobiliary disorders Cholelithiasis	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Investigations Blood glucose decreased	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Nervous system disorders Presyncope	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Nervous system disorders Thrombotic stroke	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Renal and urinary disorders Renal mass	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/59 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.	0.58% 1/173 • From the time of administration of the first dose of study drug up to a maximum of approximately 30 weeks. Data are presented as number of participants with treatment emergent AEs (serious and non-serious). The analysis was performed using the safety population, defined as all participants who received at least 1 dose of study drug and had a postbaseline safety assessment. All-cause mortality was reported for all participants randomized.