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An Exploratory Study of Rebamipide in Patients With Active Ulcerative Colitis

An Exploratory Study of Rebamipide in Patients With Active Ulcerative Colitis

124

A total of 147 subjects provided written informed consent to participate in the trial and 124 subjects were enrolled. The 124 enrolled subjects were randomized to one of the following 4 treatment groups: placebo (n = 31), rebamipide 60 mg (n = 35), rebamipide 150 mg (n = 29), and rebamipide 300 mg (n = 29). All of the randomized subjects received the investigational medicinal product (IMP). Overall, 107 subjects (24 in the placebo group, 33 in the rebamipide 60-mg group, 24 in the rebamipide 150-mg group, and 26 in the rebamipide 300-mg group) completed the trial, and 17 subjects (7 in the placebo group, 2 in the rebamipide 60-mg group, 5 in the rebamipide 150-mg group, and 3 in the rebamipide 300-mg group) were withdrawn from the trial after the first dose of the IMP. The most common reason for withdrawal was inadequate response.

- No deaths were reported during the trial. - Of the adverse events (AEs) observed, the only severe AEs were colitis ulcerative in 2 subjects (one each in the placebo and rebamipide 150-mg groups) and necrotising fasciitis in one subject in the rebamipide 150-mg group, all of which were judged to be serious AEs (SAEs). All other AEs were mild or moderate in severity. Overall, no AEs were reported at an obviously higher incidence in the rebamipide groups than in the placebo group. In addition, there were no AEs that were significantly more severe in the rebamipide groups than in the placebo group, and there were no AEs that increased in severity with increase in the dose of rebamipide. - Of the adverse drug reactions (ADRs) that were observed, the only severe ADRs were colitis ulcerative in 2 subjects (one each in the placebo and rebamipide 150-mg groups) and necrotising fasciitis in one subject in the rebamipide 150-mg group, all of which were judged to be SAEs. All other ADRs were mild or moderate in severity. Overall, no ADRs were reported at an obviously higher incidence in the rebamipide groups than in the placebo group. In addition, there were no ADRs that were significantly more severe in the rebamipide groups than in the placebo group, and there were no ADRs that increased in severity with increase in the dose of rebamipide. - None of the clinical laboratory test AEs observed were determined to be SAEs, important AEs, or severe AEs.

Clinical improvement rate, the primary endpoint, in the rebamipide 60-mg, 150-mg, and 300-mg groups was respectively 31.4%, 24.1%, and 44.4% versus 30.0% in the placebo group. This result showed no evident efficacy or dose-dependency for rebamipide within the dose range of up to 300 mg.

- Clinical remission rate at Week 6 in the placebo and rebamipide 60-mg, 150-mg, and 300-mg groups was respectively 3.3%, 2.9%, 0.0%, and 18.5%. - The rebamipide 300-mg group showed the largest mean changes from baseline at Week 6 in both total DAI score and the sum of the 3 DAI subscores ("bloody stool", "stool frequency", and "physician's global assessment"). - The rebamipide 300-mg group also had the highest proportion of subjects with a Week 6 score of 0 points for each subscore (ie, normalization of stool frequency, disappearance of bloody stool, normalization or inactivation of endoscopic findings, and normalization of physician's global assessment). - The rebamipide 300-mg group showed the largest mean change from baseline at Week 6 in total EI score.

Clinical improvement rate, the primary endpoint, in the rebamipide 60-mg, 150-mg, and 300-mg groups was respectively 31.4%, 24.1%, and 44.4% versus 30.0% in the placebo group. This result showed no evident efficacy or dose-dependency for rebamipide within the dose range of up to 300 mg. No particular safety concerns emerged at any dose studied.

No

Otsuka Pharmaceutical Co., LTD.

-

CL_OPCJ_RDA_Team@otsuka.jp

Otsuka Pharmaceutical Co., Ltd.

-

+81-3-6361-7314

completed

June. 22, 2007

Interventional

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Four-Group Comparison Study

treatment purpose

2

1)Patients aged 16 years or older
2)Patients having an insufficient response to ASA oral formulation
3)Patients shown via colonoscopy to have major lesions between the sigmoid colon and rectum

1. Patients who have a history of intestinal resection (other than appendiceal resection)
2. Patients who have a complication of malignant tumor
3. Female patients who are pregnant, lactating, or possibly pregnant, or who hope to become pregnant during the study period
4. Patients who have complications of serious cardiac, hepatic or renal impairment

Both

Active ulcerative colitis

investigational material(s)
Generic name etc : Rebamipide
INN of investigational material : Rebamipide
Therapeutic category code : 232 Agents for peptic ulcer
Dosage and Administration for Investigational material : Intracolonial (enema)

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Intracolonial (enema)

safety
efficacy
Efficacy: Clinical improvement rate, Safety: Adverse events

efficacy
- Clinical remission: a decrease of the total Disease Activity Index [DAI] scores for "bloody stools" and "endoscopic findings" to 0 points [Time Frame: 6weeks]
- Changes in the total DAI score [Time Frame: 6 weeks]
- Changes in each DAI subscore [Time Frame: 2, 4, 6weeks]
- Changes in the total Endoscopic Index (EI) score [Time Frame: 6 weeks]
- Changes in each EI subscore [Time Frame: 6 weeks]

+81-3-3353-1211

June. 28, 2007