72 Orally Dissolving, Thin Film Dexmedetomidine (BXCL501) Demonstrates Significant Reduction in Agitation Across a Range of Agitation Severity in Patients With Schizophrenia and Bipolar Disorder

Abstract

Patients with bipolar disorder and schizophrenia experience acute agitation episodes that may require urgent management to avoid escalation. BXCL501 is an investigational orally dissolving thin film of the highly selective alpha-2a adrenergic receptor agonist, dexmedetomidine, for sublingual or buccal administration. This secondary analysis of 2 Phase 3 studies of acute agitation in patients with schizophrenia or bipolar disorder evaluated efficacy by baseline agitation severity on both the PANSS-Excited Component (PEC) total and the 5 items making up the PEC (excitement, tension, hostility, uncooperativeness, poor impulse control). Data were from 2 Phase 3, randomized, placebo-controlled studies of adults with bipolar disorder or schizophrenia, with a total score of ³14 on the PEC and ³4 on at least 1 of the 5 PEC items. Patients were randomized to either BXCL501 180 mg, 120 mg, or placebo. The primary endpoint was change from baseline PEC total score at 2 hours. Moderate and severe agitation were defined as a PEC total score of 14 to 19 or >19, respectively. Calmness was rated on the Agitation and Calmness Evaluation Scale (ACES). Mean change in PEC total score from baseline to 2 hours postdose was significantly (P < .0001) greater for 180 mg (-10.4 & -10.4) and 120 mg (-8.4 & -9.0) doses of BXCL501 vs placebo (-4.7 & -4.9) for the schizophrenia & bipolar groups, respectively. Significant (P < .01) improvements from baseline to 2 hours in PEC total score were observed with BXCL501 vs placebo among subgroups with moderate or severe agitation. Significant (P < .0001) improvements from baseline in each of the 5 components of the PEC were observed with both doses of BXCL501 compared to placebo. These findings were consistent in both the schizophrenia and bipolar disorder groups. There were no severe or serious drug-related adverse events. Safety and tolerability results were comparable in both trials. In the schizophrenia study, the most common treatment emergent adverse events (TEAEs) were somnolence (22%; 86% mild, 14% moderate), dizziness (4.3%), oral hypoesthesia (4.3%), and orthostatic hypotension (4.0%) In the bipolar disorder study, the most common TEAEs were somnolence (21%; 59% mild, 41% moderate), dry mouth (5.6%), dizziness (5.6%), hypotension (5.6%), and orthostatic hypotension (4.4%). No participant was unarousable as measured by the ACES. All participants were able to self-administer the film. BXCL501, an investigational orally dissolving thin film formulation of dexmedetomidine, demonstrated consistent statistically significant improvement in PEC total score compared to placebo, regardless of baseline agitation severity in both schizophrenia and bipolar disorder groups. Statistically significant improvement in PEC total and all individual items (excitement, tension, hostility, uncooperativeness, poor impulse control) was observed with both doses in both groups. The most common TEAEs in both groups were somnolence, dizziness, and orthostatic hypotension. BXCL501 represents a potential approach for treating acute agitation in adults with schizophrenia and bipolar disorder.