Trial Outcomes & Findings for Post-marketing Clinical Study of Rebamipide in Patients With Gastric Ulcer (NCT NCT00233389)

Last Updated: 2021-06-04

Results Overview

The percentage of subjects in the analysis set in whom endoscopic assessment of gastric ulcer stage (Sakita-Miwa Classification: A1, A2, H1, H2, S1, or S2) at 8 weeks after trial treatment (H. pylori eradication therapy + IMP) was judged as healed (S1 or S2) was calculated and evaluated by group.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

301 participants

Primary outcome timeframe

Week 8

Results posted on

2021-06-04

Participant Flow

Following the eradication therapy period, 154 subjects in the rebamipide group and 147 subjects in the placebo group, excluding withdrawals during the eradication therapy period, received the investigational medicinal product (IMP) (rebamipide or placebo) for the treatment of gastric ulcer.

Participant milestones

Participant milestones
Measure	Rebamipide Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Placebo Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Overall Study STARTED	154	147
Overall Study COMPLETED	136	131
Overall Study NOT COMPLETED	18	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Rebamipide Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Placebo Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Overall Study Adverse Event	5	5
Overall Study Lack of Efficacy	11	8
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Post-marketing Clinical Study of Rebamipide in Patients With Gastric Ulcer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rebamipide n=154 Participants Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Placebo n=147 Participants Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.	Total n=301 Participants Total of all reporting groups
Age, Customized 20-39 years	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Age, Customized 40-59 years	99 Participants n=5 Participants	84 Participants n=7 Participants	183 Participants n=5 Participants
Age, Customized >=60 years	34 Participants n=5 Participants	44 Participants n=7 Participants	78 Participants n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	48 Participants n=7 Participants	100 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	99 Participants n=7 Participants	201 Participants n=5 Participants
Region of Enrollment Japan	154 Participants n=5 Participants	147 Participants n=7 Participants	301 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Full Efficacy Analysis Set: Subjects who received H. pylori eradication therapy as specified and at least one dose of the IMP.

Outcome measures

Outcome measures
Measure	Rebamipide n=154 Participants Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Placebo n=147 Participants Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Gastric Ulcer Healing Rate (Number of Subjects Whose Gastric Ulcer Was Healed/Number of Subjects Evaluated x 100) at Week 8	70.13 percentage of participants Interval 62.9 to 77.36	60.54 percentage of participants Interval 52.64 to 68.45

Adverse Events

Rebamipide

Serious events: 2 serious events

Other events: 85 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rebamipide n=154 participants at risk Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Placebo n=147 participants at risk Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Blood and lymphatic system disorders Agranulocytosis	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Blood and lymphatic system disorders Thrombocytopenia	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Nervous system disorders Cerebellar haemorrhage	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Constipation	0.00% 0/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.

Other adverse events

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Rebamipide n=154 participants at risk Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Placebo n=147 participants at risk Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Gastrointestinal disorders Cheilitis	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Constipation	3.2% 5/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Diarrhoea	17.5% 27/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	18.4% 27/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Faeces hard	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Gastric ulcer	3.2% 5/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Glossitis	0.00% 0/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	2.0% 3/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Gastrointestinal disorders Reflux oesophagitis	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
General disorders Pyrexia	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Infections and infestations Nasopharyngitis	10.4% 16/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	10.2% 15/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Injury, poisoning and procedural complications Joint sprain	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Investigations Blood urea increased	0.00% 0/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Investigations Gamma-glutamyltransferase increased	1.9% 3/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Investigations White blood cell count decreased	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Investigations White blood cell count increased	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Musculoskeletal and connective tissue disorders Arthralgia	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Musculoskeletal and connective tissue disorders Back pain	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Nervous system disorders Dizziness	0.00% 0/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Nervous system disorders Dysgeusia	9.1% 14/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	7.5% 11/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Nervous system disorders Headache	4.5% 7/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.3% 2/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.00% 0/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	2.6% 4/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	1.4% 2/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Skin and subcutaneous tissue disorders Pruritus	0.65% 1/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	2.0% 3/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.
Skin and subcutaneous tissue disorders Urticaria	1.9% 3/154 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.	0.68% 1/147 • Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal. Safety analysis set included all subjects who received the IMP at least once and from whom data on at least 1 safety endpoint were obtained after the start of IMP.