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

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00233389
• Collaborator: (none)
• Enrollment: 301
• Location: 1
• Actual Duration (Months): 16.3
• Patients Per Site Per Month: 18.4

Study Details

Study Description

Brief Summary

To examine the efficacy of continued administration of rebamipide following bacteria eradication therapy in patients with H. pylori-positive active gastric ulcer in a placebo-controlled, double-blind study

Condition or Disease	Intervention/Treatment	Phase
Stomach Ulcer	Drug: Rebamipide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 301 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Post-marketing Clinical Study of Rebamipide to Investigate the Gastric Ulcer Healing Effect of Continued Dosing Following Helicobacter Pylori Eradication Therapy
• Actual Study Start Date: Apr 30, 2004
• Actual Primary Completion Date: Sep 1, 2005
• Actual Study Completion Date: Sep 9, 2005

Outcome Measures

Primary Outcome Measures

1. Gastric Ulcer Healing Rate (Number of Subjects Whose Gastric Ulcer Was Healed/Number of Subjects Evaluated x 100) at Week 8 [Week 8]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients aged 20 years or older at time of consent

2. 1. pylori-positive patients meeting both of the following criteria:• Assessed as H. pylori-positive by rapid urease test and/or 13C-urea breath test at pre-study examination, • Assessed as H. pylori-antibody-positive by urine-based test after obtaining informed consent

3. Patients endoscopically diagnosed with gastric ulcer meeting the following criteria:• Active (A1- or A2-stage by Sakita/Miwa classification）, • Solitary, • Longitudinal diameter: ->5 mm

4. Patients who have not received proton pump inhibitors (PPIs), antibacterial agents, or antiprotozoal agents within 1 week prior to endoscopy

Exclusion Criteria:

1. Patients who have previously received H. pylori eradication therapy

2. Patients with acute gastric ulcer

3. Patients with linear ulcer

4. Patients with complication of duodenal ulcer (excluding cicatrix)

5. Patients who have undergone upper-GI tract or vagal nerve resection

6. Patients who are unsuitable for pharmacotherapy, e.g., with perforation or pyloric stenosis

7. Patients with gastric ulcer considered likely to induce massive hemorrhage (e.g., with obviously exposed blood vessels at lesion sites)

8. Patients with a history of amoxicillin shock

9. Patients with infectious mononucleosis

10. Patients with severe renal disorders

11. Patients with a history of hypersensitivity to penicillins, clarithromycin, lansoprazole, or rebamipide

12. Patients who have been treated with drugs contraindicated to clarithromycin, such as terfenadine, cisapride, and pimozide

13. Patients who are pregnant, possibly pregnant, lactating, or who desire to become pregnant during the study

14. Patients who are otherwise judged inappropriate for inclusion in the study by the investigator or subinvestigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Otsuka Pharmaceutical Co., Ltd.	Tokyo		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Katsuhisa Saito, Division of New Product Evaluation and Development

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00233389
• Other Study ID Numbers: C03700-003; JapicCTI-050035
• First Posted: Oct 5, 2005
• Last Update Posted: Jun 4, 2021
• Last Verified: May 1, 2021

• Additional relevant MeSH terms: Stomach Ulcer; Ulcer; Rebamipide

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Rebamipide	Placebo
Arm/Group Description	Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Period Title: Overall Study
STARTED	154	147
COMPLETED	136	131
NOT COMPLETED	18	16

Baseline Characteristics

Arm/Group Title	Rebamipide	Placebo	Total
Arm/Group Description	Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.	Total of all reporting groups
Overall Participants	154	147	301
Age, Customized (Count of Participants)
20-39 years	21 13.6%	19 12.9%	40 13.3%
40-59 years	99 64.3%	84 57.1%	183 60.8%
>=60 years	34 22.1%	44 29.9%	78 25.9%
Sex: Female, Male (Count of Participants)
Female	52 33.8%	48 32.7%	100 33.2%
Male	102 66.2%	99 67.3%	201 66.8%
Region of Enrollment (Count of Participants)
Japan	154 100%	147 100%	301 100%

Outcome Measures

1. Primary Outcome

Title	Gastric Ulcer Healing Rate (Number of Subjects Whose Gastric Ulcer Was Healed/Number of Subjects Evaluated x 100) at Week 8
Description	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.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rebamipide	Placebo
Arm/Group Description	Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.	Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
Measure Participants	154	147
Number (95% Confidence Interval) [percentage of participants]	70.13 45.5%	60.54 41.2%

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from the start of IMP administration to 7 weeks or withdrawal.
Adverse Event Reporting Description	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.
Arm/Group Title	Rebamipide		Placebo
Arm/Group Description	Following 1 week of H. pylori eradication therapy, a rebamipide 100 mg tablet was administered orally three times a day for 7 weeks.		Following 1 week of H. pylori eradication therapy, a placebo tablet was administered orally three times a day for 7 weeks.
All Cause Mortality
	Rebamipide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/154 (0%)		0/147 (0%)
Serious Adverse Events
	Rebamipide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/154 (1.3%)		1/147 (0.7%)
Blood and lymphatic system disorders
Agranulocytosis	1/154 (0.6%)		0/147 (0%)
Thrombocytopenia	1/154 (0.6%)		0/147 (0%)
Gastrointestinal disorders
Constipation	0/154 (0%)		1/147 (0.7%)
Nervous system disorders
Cerebellar haemorrhage	1/154 (0.6%)		0/147 (0%)
Other (Not Including Serious) Adverse Events
	Rebamipide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/154 (55.2%)		75/147 (51%)
Gastrointestinal disorders
Cheilitis	1/154 (0.6%)		2/147 (1.4%)
Constipation	5/154 (3.2%)		2/147 (1.4%)
Diarrhoea	27/154 (17.5%)		27/147 (18.4%)
Faeces hard	1/154 (0.6%)		2/147 (1.4%)
Gastric ulcer	5/154 (3.2%)		2/147 (1.4%)
Glossitis	0/154 (0%)		3/147 (2%)
Reflux oesophagitis	2/154 (1.3%)		1/147 (0.7%)
General disorders
Pyrexia	2/154 (1.3%)		0/147 (0%)
Infections and infestations
Nasopharyngitis	16/154 (10.4%)		15/147 (10.2%)
Injury, poisoning and procedural complications
Joint sprain	2/154 (1.3%)		0/147 (0%)
Investigations
Blood urea increased	0/154 (0%)		2/147 (1.4%)
Gamma-glutamyltransferase increased	3/154 (1.9%)		1/147 (0.7%)
White blood cell count decreased	2/154 (1.3%)		1/147 (0.7%)
White blood cell count increased	2/154 (1.3%)		1/147 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/154 (1.3%)		0/147 (0%)
Back pain	1/154 (0.6%)		2/147 (1.4%)
Nervous system disorders
Dizziness	0/154 (0%)		2/147 (1.4%)
Dysgeusia	14/154 (9.1%)		11/147 (7.5%)
Headache	7/154 (4.5%)		1/147 (0.7%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	2/154 (1.3%)		0/147 (0%)
Upper respiratory tract inflammation	4/154 (2.6%)		2/147 (1.4%)
Skin and subcutaneous tissue disorders
Eczema	0/154 (0%)		2/147 (1.4%)
Pruritus	1/154 (0.6%)		3/147 (2%)
Urticaria	3/154 (1.9%)		1/147 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.