PII-031 - LONGITUDINAL EFFICACY ANALYSIS OF THE SUBLINGUAL FILM FORMULATION OF DEXMEDETOMIDINE (BXCL501) FOR THE TREATMENT OF ACUTE AGITATION ASSOCIATED WITH SCHIZOPHRENIA AND BIPOLAR DISORDER.

F. Jonsson¹, H. Lagraauw², C. Lathia³, A. Adedoyin³; ¹qPharmetra, LLC, Stockholm, Sweden, ²qPharmetra, LLC, Nijmegan, The Netherlands, ³BioXcel Therapeutics, New Haven, CT, USA.

Background: BXCL501 is an orally dissolving film of dexmedetomidine HCl that was developed for sublingual or buccal self-administration as treatment for acute agitation associated with schizophrenia and bipolar disorders in adults. The pharmacokinetic-pharmacodynamic (PKPD) examination of efficacy presented here uses a recently developed pharmacokinetic (PK) model.

Methods: Data analyzed were from in one Phase 1b and two large Phase 3 studies in adults with schizophrenia or bipolar disorder. The model was developed using an integrated analysis of the exposure-response relationship between dexmedetomidine PK and two rating scales measuring agitation and calmness, the Positive and Negative Syndrome Scale - Excited Component (PEC) and the Agitation and Calmness Evaluation Scale (ACES) after administration of sublingualBXCL501 doses between 20 and 180 mcg. The analysis was carried out using NONMEM version 7.4.

Results: The final model was a joint continuous model for ACES and PEC describing a direct linear relationship between plasma dexmedetomidine concentration and response on the PEC scale without effect delay. A baseline PEC score of 17.5 was estimated. Simulations demonstrated response to placebo, but with significant additional dose-dependent treatment effect. In addition, a high responder (≥40% decrease in PEC score) rate at both approved clinical doses of 120 and 180 mcg, without significant sedation, was demonstrated.

Conclusion: An exposure-response model with linear treatment effect on PEC/ACES was developed for sublingual dexmedetomidine (BXCL501) in the acute treatment of agitation in adults with schizophrenia or bipolar disorder. The developed model is amenable for exploring different treatment regimens to optimize dosing.