Positive results were announced from two pivotal phase 3 trials, SERENITY I and II, evaluating BXCL501 (dexmedetomidine; BioXcel Therapeutics) for the acute treatment of agitation in schizophrenia and bipolar disorder.

Dexmedetomidine is currently available as a solution for intravenous infusion for use in clinical anesthesia and sedation in an intensive care setting. BXCL501 is an investigational proprietary sublingual thin film of dexmedetomidine, a selective alpha-2a receptor agonist.

The multicenter, double-blind, placebo-controlled trials assessed the efficacy and safety of BXCL501 in 381 adults with schizophrenia (SERENITY I) and 378 adults with bipolar disorder (SERENITY II). Patients were randomized 1:1:1 to receive either BXCL501 120mcg, 180mcg, or placebo. The primary end point was the absolute change from baseline in acute agitation as measured by the Positive and Negative Syndrome Scale-Excitatory Component (“PEC”) score at 2 hours. 

Findings from both studies showed that BXCL501 met the primary end point achieving statistically significant and clinically meaningful reductions in the PEC score at 2 hours vs placebo (P <.0001). In SERENITY I, 67% of patients treated with the 120mcg dose and 87% of patients treated with the 180mcg dose were considered responders (defined as a ≥40% reduction in PEC scores) compared with 34% of patients in the placebo arm. In SERENITY II, the response rates were 69% and 85% for the 120mcg and 180mcg doses, respectively, vs 37% for placebo.

Both studies also met the key secondary end point achieving highly statistically significant improvements in PEC score with BXCL501 at 30 minutes, 45 minutes, 60 minutes and 90 minutes. Moreover, BXCL501 was associated with significant improvements as early as 20 minutes in patients with bipolar disorder at both doses (P <.025), and as early as 20 minutes in patients with schizophrenia at a dose of 180mcg. Additional analysis of BXCL501 using the Agitation and Calmness Evaluation Scale (ACES), and Clinical Global Impression – Improvement Scale (CGI-I) demonstrated statistically significant improvements compared with placebo.

With regard to safety, BXCL501 was found to be well tolerated with all adverse events reported as being mild to moderate in severity. The most common adverse events in both studies were somnolence (22% for 180mcg, 21% for 120mcg, 6% for placebo), dry mouth (4.4%, 7.5%, 1.2%, respectively), and dizziness (6.0%, 3.9%, 0.8%, respectively).

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“These compelling phase 3 results show that BXCL501, if approved, has the potential to become an important new treatment option for patients suffering from acute agitation,” commented Vimal Mehta, PhD, Chief Executive Officer of BTI. “We are extremely pleased that rapid and robust reductions in agitation were demonstrated in both patient populations despite differing neuropsychiatric diagnoses.”

The Food and Drug Administration (FDA) previously granted Fast Track designation to BXCL501 for this indication. The Company plans to submit a New Drug Application with the FDA in the first quarter of 2021.

BXCL501 is also being investigated for the treatment of agitation associated with dementia in a phase 1b/2 trial (TRANQUILITY), as well as for the treatment of opioid withdrawal symptoms in a phase 1b/2 study (RELEASE).

For more information visit bioxceltherapeutics.com.