First dose-ranging study of remimazolam in Japanese patients undergoing gastrointestinal endoscopy: Phase II investigator-initiated clinical trial

Objectives: Remimazolam, an ultra-short-acting benzodiazepine, has been used for procedural sedation in the United States. We conducted an investigator-initiated clinical trial to determine the appropriate dose of remimazolam required for sedation during gastrointestinal endoscopy in Japanese subjects. Methods: In this single-center, open-label, uncontrolled, phase II trial, a three-stage cohort investigated the appropriate initial and additional doses of remimazolam required for gastrointestinal endoscopy. This study was designed with advice from the Pharmaceuticals and Medical Devices Agency. The initial and additional doses were 2 mg and 1 mg/dose, 3 mg and 1 mg/dose, and 5 mg and 2 mg/dose in cohorts 1, 2, and 3, respectively. Each cohort included 10 cases of upper gastrointestinal endoscopy and colonoscopy. The primary end-point was the success rate of sedation during gastrointestinal endoscopy. Results: Sedation was successful in all gastrointestinal endoscopies in cohorts 1 and 2. In cohort 1, sedation was achieved in five (25.0%) and 10 (50.0%) participants with the initial dose and total dose (initial dose + additional dose ≤ the initial dose of the next cohort), respectively, before endoscopy. In cohort 2, sedation was achieved in 11 (55.0%) and 18 (90.0%) participants with the initial dose and total dose, respectively, before endoscopy. No patient in either cohort lost consciousness or required flumazenil or manual ventilation. Conclusion: Initial and additional doses of 3 mg and 1 mg/dose of remimazolam, respectively, were shown to be effective and safe for sedation during gastrointestinal endoscopy in Japanese patients.