Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, Double-Blind, Active Control, Noninferiority, Multicenter, Phase 3 Study

BACKGROUND/AIMS: The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta(Ⓡ) (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis. METHODS: This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups AD-203 twice daily or Mucosta(Ⓡ) thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta(Ⓡ), n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta(Ⓡ), n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated. RESULTS: According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta(Ⓡ)-treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta(Ⓡ)-treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta(Ⓡ)-treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates. CONCLUSIONS: The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta(Ⓡ)) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.