EFFICACY OF SUBLINGUAL DEXMEDETOMIDINE IN THE HOME SETTING FOR REDUCTION IN AGITATION ACROSS BASELINE SEVERITY OF SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

Background

BXCL501 is a sublingual film formulation of dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, which has been approved for treatment of episodes of agitation in patients with schizophrenia or bipolar disorders under the supervision of a healthcare provider. In the home setting, where most episodes of agitation occur and no healthcare provider is present, there are no FDA-approved therapies for this indication. In order to address this patient need, a Phase 3 safety trial of the lower of the two approved doses of BXCL501 (120mcg) was initiated following consultations with the FDA. The primary objective of the trial was to investigate whether patients could safely self-administer BXCL501 in the absence of a healthcare provider. In addition, patient-reported efficacy data were collected as an exploratory objective.

Methods

A randomized, double-blind, placebo-controlled, Phase 3, 12-week trial (SERENITY At-home, NCT05658510) in adult patients with episodes of agitation associated with a primary diagnosis of bipolar disorders or schizophrenia in the community (at home) setting. The primary objective of the trial was safety and tolerability. Efficacy was also evaluated as an exploratory objective. The main exploratory efficacy measure was a modified clinical global impression – severity (mCGI-S). mCGI-S was scored by patients themselves and by caregivers/informants, if present, on a scale of 0 (no agitation) to 3 (severe agitation). This report describes the efficacy analyses based on pre-dose levels of symptom severity.

Results

Primary data analyses indicated that BXCL501 was safe and tolerable when administered in unsupervised setting. Efficacy data were available for all 208 patients whose agitation episodes were treated with BXCL501 or placebo. In these patients, over 2437 episodes, a greater reduction in symptoms was seen with BXCL501 compared with placebo (P < 0.05). In the severe symptoms subset, the mean reduction was 2.4 in the BXCL501 group and 1.6 with placebo. The differences were smaller in the moderate and mild subsets, but they both trended in the same direction (1.3 vs 1.2 and 0.6 vs 0.4, respectively). The reductions remained consistent throughout the 3-month study, with no indication of attenuation of benefit with repeat administration. In addition, a greater proportion of patients experienced full resolution of symptoms with BXCL501 compared with placebo across the episodes regardless of severity at baseline (P < 0.0005).

Conclusions

In this pivotal safety study, as-needed doses of sublingual dexmedetomidine 120 mcg were safe, well tolerated, and reduced the severity of agitation in subjects with schizophrenia or bipolar disorder over a 12-week treatment period when administered on an as-needed basis. Over repeat dosing, the reduction in symptoms remained consistent throughout the duration of the trial. Greater reductions in symptoms were observed with BXCL501 than with placebo regardless of pre-dose severity, but the largest differences were observed among patients who experiences severe symptoms for the measured episode.