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The investigative treatment BXCL501 was found to be effective at reducing agitation in schizophrenia and bipolar disorder, the phase III SERENITY I and II trials found.

In the first trial of 380 patients with schizophrenia, treatment with 120 µg of the oral rapidly dissolving film yielded an average 8.5-point reduction in Positive and Negative Syndrome Scale (PANSS)-Excited Component (PEC) total score from baseline within 2 hours versus a 4.8-point improvement with placebo -- meeting the trial's primary endpoint -- reported Leslie Citrome, MD, MPH, of New York Medical College in Valhalla, and colleagues.

Those treated with a higher dose -- 180 µg -- of BXCL501 saw a 10.3-point drop in total score within 2 hours of dosing, the group reported at the American Psychiatric Association (APA) virtual meeting.

"BXCL501 is an investigational, proprietary, orally dissolving thin film formulation of dexmedetomidine, a highly selective alpha-2a receptor agonist," Citrome explained to 名媛直播, adding that it "is believed to potentially target a causal mechanism of agitation."

BXCL501 has been granted a by the FDA for this indication, he noted. "If approved, BXCL501 could be the first acute treatment for agitation associated with schizophrenia and bipolar disorder that may work through alpha-2a receptor agonism, is absorbed in the oral mucosa, and does not require injection into a muscle."

This significant improvement in PEC score was also seen as early as only 20 minutes after ingesting the 180 µg dose, and only 30 minutes with the 120 µg dose.

After 2 hours, 79.1% and 88.8% of those on BXCL501 120 µg and 180 µg were considered responders to treatment versus only 40% of those on placebo.

Those on active treatment also saw significantly better Clinical Global Impressions-Improvement (CGI-I) Scale scores versus placebo, the first of the secondary endpoints. Two hours after dosing, those on BXCL501 120 µg and 180 µg had CGI-I scores of 2.0 and 1.6, respectively, compared with 2.8 for those on placebo.

Meeting another secondary endpoint, average change in Agitation-Calmness Evaluation Scale (ACES) score from baseline was also significantly better for the active treatment groups: 2.7 (120 µg), 3.7 (180 µg), and 1.1 (placebo).

Average age of trial participants was 48 years (age range 18-75), and about half were women. At baseline, average PEC total score was 18. All had a DSM-5 diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder, and presented with acute agitation.

Treatment was self-administered and a repeat half dose (90 µg or 60 µg) could be given 2 hours following the initial dose if the PEC score change from baseline was less than 40% and there were no safety concerns. However, the maximum number of repeat doses was capped at two within 12 hours of the initial dose.

"BXCL501 is placed either under the tongue -- sublingual -- or between the lip and cheek -- buccal -- so that it can dissolve quickly in the oral cavity and be absorbed through the oral mucosa," explained Citrome.

No serious adverse events were reported, but about 35% of those on active treatment experienced a treatment-related adverse event versus 12% on placebo. The most common events reported were somnolence (22%), dry mouth (6%), and hypotension (4%). There weren't any clinically meaningful changes in PR interval, QRS duration, or corrected QT interval by Fridericia.

In the SERENITY II trial, which included 380 patients with bipolar I or II disorder, similar improvements in agitation were achieved.

In this 1:1:1 randomized trial, those on BXCL501 120 µg and 180 µg saw an average drop in PEC total score from baseline of 9.1 and 10.4, respectively, after 2 hours versus a drop of only 5.0 with placebo.

After 2 hours, those who self-administered BXCL501 also achieved significant improvements in ACES score and CGI-I score.

Overall, the safety profile was similar to that seen in patients with schizophrenia.

"BioXcel has submitted an NDA [new drug application] to the U.S. FDA to bring BXCL501 to patients and healthcare providers as a non-invasive acute treatment of agitation associated with schizophrenia and bipolar disorder," Citrome concluded, noting that BioXcel is hopeful for a potential May acceptance.

BXCL501 has also been evaluated in the phase Ib/II TRANQUILITY trial for acute treatment of agitation associated with dementia, he added.

"BXCL501 received and fast track status from the U.S. FDA for this potential indication. In the U.S., there are currently no approved medications to treat agitation associated with dementia, including Alzheimer's dementia," Citrome said. "Agitation is a symptom that affects many patients with Alzheimer's disease."

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