BXCL501 Led to Fast, Safe, Durable Drop in Agitation in Dementia Patients

BXCL501, BioXcel Therapeutics’ experimental therapy for the treatment of agitation associated with dementia, was found to be well-tolerated and able to rapidly and sustainably lower agitation in patients with different forms of dementia, including Alzheimer’s disease.

These top-line findings from TRANQUILITY, BioXcel‘s Phase 1b/2 clinical trial (NCT04251910), are expected to support the therapy’s continued development as a treatment for agitation associated with dementia.

“We are very encouraged by the promising topline results from the TRANQUILITY study, which was designed to identify a recommended dose of BXCL501 for a potential pivotal study in dementia patients suffering from agitation,” Vimal Mehta, CEO of BioXcel, said in a press release.

“Based on the results observed, we believe BXCL501 has broad potential in treating the full spectrum of agitation in patients with dementia. We look forward to advancing BXCL501 into a late-stage study this year following dialogue with the FDA,” Mehta said.

A proprietary orally dissolving formulation of dexmedetomidine, BXCL501 is a selective agonist of alpha-2a adrenergic receptors with potent anti-anxyolitic and sedative properties. It is normally used to sedate patients undergoing invasive procedures or in intensive care settings.

BXCL501 is easy to administer, and designed to rapidly trigger a calming effect, without causing excessive sedation. BioXcel also believes that BXCL501 potentially may cause fewer side effects than other antipsychotics currently used in clinical practice.

The experimental therapy’s safety and efficacy in treating acute agitation associated with different forms of dementia are currently being investigated in the randomized, dose-finding TRANQUILITY trial.

It enrolled a total of 54 patients, ages 65 and older, living in assisted living residencies, who had episodes of acute agitation associated with dementia. Most of them (87%) had Alzheimer’s. 

The participants were randomly assigned to receive an under-the-tongue (sublingual) dissolving thin film containing one of three doses — 30, 60, or 90 mcg — of BXCL501 or a matched placebo. In addition to assessing the therapy’s safety and tolerability, trial investigators evaluated its effectiveness at reducing agitation. 

Safety assessments revealed BXCL501 was well-tolerated and did not cause any severe or serious side effects. Daytime sleepiness, known clinically as somnolence, was the most common side effect reported in the trial, and was classified as mild in most cases. Some patients treated with the therapy’s higher dose also experienced dizziness and episodes of orthostasis, or low blood pressure shortly after standing.

In subsequent analyses, the investigators focused on assessing the effects of the two lower doses of BXCL501, as patients receiving the 90 mcg dose in TRANQUILITY were found to have a much higher exposure to the medication compared with those dosed in earlier trials.

When given at a dose of 60 mcg, BXCL501 significantly reduced the scores of three scales — the Positive and Negative Syndrome Scale-Excitatory Component (PEC), the Pittsburgh Agitation Scale (PAS), and the Modified Cohen-Mansfield Agitation Inventory (Mod-CMAI) — that were used to measure patients’ agitation levels. Lower scores reflect less agitation.

These clinically meaningful reductions were observed in a period of two hours following dosing. In the case of PEC scores, differences between patients treated with BXCL501 at a dose of 60 mcg and those given a placebo started to be seen as early as 30 minutes following dosing. The differences became significant after one hour, and lasted up to eight hours post-treatment. 

Statistically significant improvements in the scores of two other agitation scales — the Agitation and Calmness Evaluation Scale (ACES) and Clinical Global Impression-Improvement Scale (CGI-I) — also were seen in patients treated with BXCL501 at a dose of 60 mcg, compared with those given a placebo, within two hours following dosing. 

Patients receiving BXCL501 at a lower dose of 30 mcg also saw their scores improve on all scales.