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
Gwang Ha Kim,
Hang Lak Lee,
Moon Kyung Joo,
Hong Jun Park,
Sung Woo Jung,
Ok-Jae Lee,
Hyungkil Kim,
Hoon Jai Chun,
Soo Teik Lee,
Ji Won Kim,
Han Ho Jeon,
Il-Kwun Chung,
Hyun-Soo Kim,
Dong Ho Lee,
Kyoung-Oh Kim,
Yun Jeong Lim,
Seun-Ja Park,
Soo-Jeong Cho,
Byung-Wook Kim,
Kwang Hyun Ko,
Seong Woo Jeon,
Jae Gyu Kim,
In-Kyung Sung,
Tae Nyeun Kim,
Jae Kyu Sung,
Jong-Jae Park
Affiliations
Gwang Ha Kim
Department of Internal Medicine, Pusan National University College of Medicine, and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
Hang Lak Lee
Department of Internal Medicine, Hanyang University Hospital, Seoul, Korea
Moon Kyung Joo
Division of Gastroenterology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
Hong Jun Park
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
Sung Woo Jung
Division of Gastroenterology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
Ok-Jae Lee
Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Korea
Hyungkil Kim
Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
Hoon Jai Chun
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, Seoul, Korea
Soo Teik Lee
Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Korea
Ji Won Kim
Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University of College of Medicine, Seoul, Korea
Han Ho Jeon
Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
Il-Kwun Chung
Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
Hyun-Soo Kim
Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
Dong Ho Lee
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
Kyoung-Oh Kim
Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
Yun Jeong Lim
Department of Internal Medicine, Dongguk University College of Medicine, Seoul, Korea
Seun-Ja Park
Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
Soo-Jeong Cho
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Byung-Wook Kim
Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Kwang Hyun Ko
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea
Seong Woo Jeon
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
Jae Gyu Kim
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
In-Kyung Sung
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
Tae Nyeun Kim
Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
Jae Kyu Sung
Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
Jong-Jae Park
Division of Gastroenterology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
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.
