BioXcel planning pivotal trial of BXCL501 for Alzheimer’s agitation

In Care study to test therapy in nursing, assisted living facility patients

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by Andrea Lobo |

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BioXcel Therapeutics plans to launch a pivotal Phase 3 in-care trial — one involving patients in nursing or assisted living facilities — to continue to evaluate BXCL501 (dexmedetomidine sublingual film) for the acute treatment of agitation in patients with Alzheimer’s disease dementia.

BXCL501 is an experimental orally dissolving film formulation of dexmedetomidine that has shown benefits in treating agitation episodes in people with Alzheimer’s who also experience related dementia.

This trial aims to provide additional efficacy and safety data on BXCL501 at a 60 microgram (mcg) dose, given over 12 weeks or about three months.

“This represents a major milestone since there is no U.S. regulatory precedent for episodic treatment of [agitation associated with Alzheimer’s dementia],” Vincent O’Neill, MD, BioXcel’s chief of product development and medical officer, said in a company press release. “We are now intensely focused on advancing this important program,” he added.

BioXcel is seeking to expand the number of Alzheimer’s patients treated with its investigational therapy, which already has been evaluated in earlier Phase 3 trials dubbed TRANQUILITY II and TRANQUILITY III. The company’s decision to begin the TRANQUILITY in-care trial leverages two meetings with the U.S. Food and Drug Administration (FDA), which clarified the next steps for the clinical development of BXCL501.

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Active ingredient in BXCL501 has sedative and anti-anxiety effects

The active agent in BXCL501 is dexmedetomidine, which activates alpha-2a adrenergic receptors in the brain, having sedative and anti-anxiety effects. Igalmi, another oral film formulation of dexmedetomidine developed by BioXcel, is approved in the U.S. to treat agitation in people with schizophrenia or bipolar disorder.

The planned trial is expected to enroll about 150 people with Alzheimer’s disease dementia and episodic agitation, who live in nursing or assisted living facilities, and in memory care units.  The company also plans to include about 20 patients evaluated in the home setting. Included in the trial will be patients, age 55 and older, with mild to severe dementia and cognitive impairment, as measured by the mini-mental state examination (MMSE). Each will be randomly assigned to the treatment or a placebo.

The under-the-tongue, or sublingual, dissolving thin film contains 60 mcg of BXCL501. It or a placebo will be self-administered by the patients whenever agitation occurs.

The trial’s main efficacy goal is to evaluate changes in agitation, measured by the Positive and Negative Syndrome Scale-Excitatory Component (PEC). The assessment will be done within two hours of each dose, and compared with measures at the trial’s start, or baseline. Continued evaluations also will be performed using the Pittsburgh Agitation Scale (PAS). In both scales, lower scores indicate less agitation.

The researchers also plan to include complementary efficacy measures, particularly the global impression of change in agitation.

“The design of our upcoming TRANQUILITY In-Care trial largely mirrors TRANQUILITY II, which demonstrated positive efficacy and safety results with a 60 mcg dose of BXCL501,” O’Neill said.

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Treatment seen to reduce agitation in patients with different forms of dementia

Topline data from the Phase 3 TRANQUILITY II trial (NCT05271552) were reported by the company last year. Use of the therapy was shown to significantly ease episodes of agitation in Alzheimer’s disease patients with mild to moderate dementia who did not require much daily assistance.

A total of 149 patients were included in the study, and all were given the medication, or a placebo, whenever they experienced an agitation episode.  The results showed that patients receiving the 60 mcg treatment dose saw a 39% reduction in the PEC score compared with those on the placebo.

The treatment also was found to be generally safe and well tolerated, with no serious side effects reported. Another similar trial, TRANQUILITY III (NCT05665088), which was assessing the therapy in patients with more advanced dementia, was terminated last year due to business reasons not related to safety or efficacy.

Previous positive data from the Phase 1/ 2 TRANQUILITY trial (NCT04251910), completed in 2022, showed the therapy was well tolerated and could rapidly decrease agitation in patients with different forms of dementia.

BXCL501 received FDA Breakthrough Therapy Designation in 2021 for the treatment of agitation associated with dementia. That designation is meant to accelerate the development and review of therapy candidates for serious or life-threatening diseases or conditions.