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First Patient Dosed With BXCL501 in Phase 3 TRANQUILITY II Trial in Alzheimer Agitation

In a prior phase 1b/2 study, BXCL501 demonstrated statistically significant reductions in agitation measures with both the 30- and 60-mcg doses as measured by multiple scales with no severe or serious adverse events.

According to a new announcement, patient dosing has begun in the TRANQUILITY II study, a pivotal phase 3 trial evaluating the efficacy and safety of BXCL501 (BioXcel Therapeutics), an orally dissolving thin film formulation of dexmedetomidine for the acute treatment of agitation in Alzheimer disease (AD).1 In April 2022, BXCL501 gained FDA approval for agitation associated with schizophrenia or bipolar I or II disorder in adults.2

Initiated in December 2021, the trial is part of a larger phase 3 program that also includes TRANQUILITY III, a randomized, placebo-controlled, adaptive study that is parallel in design to TRANQUILITY II. Both studies are expected to enroll approximately 150 patients with dementia older than the age of 65 years with change from baseline in Positive and Negative Syndrome Scale-Excitatory Component (PEC) as the primary end point.

"There are an estimated 100 million agitation episodes annually in the US associated with Alzheimer’s disease, which have a devastating impact on patients and their caregivers,” Robert Risinger, MD, chief medical officer, BioXcel Therapeutics, said in a statement.1 "We are also expanding TRANQUILITY II to more than 10 clinical trial sites in the US and with no current FDA approved treatments for agitation associated with this disease, we are making strong and swift efforts to potentially bring BXCL501 and its proven ability to address agitation to this large market."

When agitation occurs, patients in the study will self-administer 40-mcg or 60-mcg dose of BXCL501, or placebo over a 3-month period. PEC scores will be recorded at 2 hours after initial dose and after subsequent doses as well. Following completion of the phase 3 trials, participants will be eligible to enroll in a 52-week, open-label safety study to evaluate the efficacy of continued use of BXCL501.

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The 2 studies slightly differ in terms of activities of daily living (ADL) criteria. TRANQUILITY II will be made up of patients in assisted living or residential families or require minimal assistance with ADL, whereas TRANQUILITY III is a more severely hindered population, consisting of patients in nursing homes who have moderate to severe dementia and require moderate or greater assistance with ADL.

The company’s decision to continue the evaluation of both the 40- and 60-mcg doses of BXCL501 was supported by recent data from the phase 1b/2 TRANQUILITY (NCT04251910) ascending dose finding study. The study’s primary safety and tolerability end points were met, with no severe or serious adverse events, among a cohort of 54 patients in assisted living facilities with agitation related to dementia, 87% of whom had AD.3

In April 2022, the FDA approved BXCL501 sublingual film for the acute treatment agitation associated with schizophrenia or bipolar I or II disorder in adults. Expected to launch in the second quarter of 2022, the approval was based on data from SERENITY I and SERENITY II, 2 pivotal randomized, double-blinded, placebo-controlled, parallel group studies.4

In both trials, BXCL501 in 120-mcg and 180-mcg doses met its primary end point in change from baseline in PEC total score assessed at 2 hours. The mean changes from baseline in PEC total score were –10.4 (SD, 4.4) for sublingual BXCL501 180-mcg and –9.0 (SD, 5.3) for 120-mcg, compared with –4.9 (SD, 4.7) for placebo. On the key secondary end point, statistically significant treatment effects were evident 20 minutes after initial treatment for both doses (180-mcg: P = .007; 120-mcg: P = .009) compared with placebo.

Risinger added, "we believe the recent FDA approval of BXCL501 for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults has laid a strong foundation for pursuing this Alzheimer’s-related agitation program to potentially address this debilitating symptom for patients."1

1. BioXcel Therapeutics announces first patient dosed in TRANQUILITY II phase 3 trial for acute treatment of agitation in patients with Alzheimer disease. News release. BioXcel Therapeutics. May 3, 2022. Accessed May 5, 2022. https://www.biospace.com/article/releases/bioxcel-therapeutics-announces-first-patient-dosed-in-tranquility-ii-phase-3-trial-for-acute-treatment-of-agitation-in-patients-with-alzheimer-s-disease/

2. BioXcel Therapeutics announces FDA approval of IGALMI (dexmedetomide) sublingual film for acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. News release. BioXcel Therapeutics. April 6, 2022. Accessed May 5, 2022. https://www.globenewswire.com/news-release/2022/04/06/2417422/0/en/BioXcel-Therapeutics-Announces-FDA-Approval-of-IGALMI-dexmedetomidine-Sublingual-Film-for-Acute-Treatment-of-Agitation-Associated-with-Schizophrenia-or-Bipolar-I-or-II-Disorder-in-.html#:~:text=The%20Company's%20commercial%20product%2C%20IGALMI,or%20II%20disorder%20in%20adults.

3. BioXcel Therapeutics announces BXCL501 met the primary and all secondary end points in the TRANQUILITY phase 1b/2 study for the acute treatment of agitation in dementia, including Alzheimer disease. News release. BioXcel Therapeutics. January 5, 2021. Accessed May 5, 2022. https://www.globenewswire.com/news-release/2021/01/05/2153316/0/en/BioXcel-Therapeutics-Announces-BXCL501-Met-the-Primary-and-All-Secondary-Endpoints-in-the-TRANQUILITY-Phase-1b-2-Study-for-the-Acute-Treatment-of-Agitation-in-Dementia-including-Al.html

4. BioXcel Therapeutics announces journal of the American Medical Association publication of data from SERENITY II pivotal phase 3 trial evaluating BXCL501 in bipolar disorders. News release. BioXcel Therapeutics. February 22, 2022. Accessed May 5, 2022. https://www.globenewswire.com/news-release/2022/02/22/2389630/0/en/BioXcel-Therapeutics-Announces-Journal-of-the-American-Medical-Association-Publication-of-Data-from-SERENITY-II-Pivotal-Phase-3-Trial-Evaluating-BXCL501-in-Bipolar-Disorders.html