T-24: A Phase 1 pilot trial to explore safety, pharmacokinetics, and bioavailability of intranasal remimazolam in healthy subjects

Poster Presenter

Lynn Roy Webster

Vice President, Scientific Affairs
PRA Health Sciences
United States

Objectives

Evaluate the feasibility and safety of intranasal administration of remimazolam Assess the pharmacokinetic and pharmacodynamic characteristics of intranasally administered remimazolam.

Method

Methods: A single-center, randomized, double blind, placebo and active controlled, 9-period crossover, Phase 1 trial in 12 healthy male volunteers was conducted. Each subject received RMZ as iv (4mg), as intranasal powder and solution (10, 20, and 40mg), and placebo powder and solution.

Results

Out of 12 males enrolled, 10 completed all 9 cross-over periods. Mean age was 28 years; mean BMI 23 kg/m². Bioavailability for the powder based on AUC and Cmax was ~50% and ~20% respectively across all doses. Similar AUC and Cmax were obtained for the 10mg solution dose but did not increase proportionally with the 20mg and 40mg solution dose. Across all doses, Tmax was 13min. for powder and 9min. for solution. Learning/reaction tests and alertness/drowsiness VAS showed some effects with the 20 and 40mg doses; tentatively stronger with powder than solution. There were no SAEs. 1 subject discontinued due to “toothache”. Most frequently reported AEs were “BP diastolic increased and decreased” (N= 8 each), “somnolence” (N= 8), “euphoric mood” (N= 7) and “nasal discomfort” (N= 7). All AEs resolved by the end of the trial; the vast majority spontaneously.

Conclusion

Conclusion: Intranasal administration of RMZ was safe and well tolerated. Intranasal powder especially resulted in plasma concentrations warranting further exploration regarding other therapeutic options.