Sub-Lingual Dexmedetomidine in Agitation Associated With Dementia

A Phase Ib/II, Multicenter, Randomized, Double Blind, Placebo Controlled, Ascending Dose Finding, Efficacy, Pharmacokinetic and Safety Study of BXCL501 In Agitation Associated With Dementia

This is an adaptive Phase 1b/2 trial design. It is randomized, double-blind, placebo-controlled, multiple ascending dose study assessing efficacy, pharmacokinetics, safety and tolerability of BXCL-501 dosing in adult (65 years and older) males and females with acute agitation associated with dementia. Evaluation of 3 doses are planned.

This is a Phase 1b/2 randomized, double-blind, placebo controlled, ascending dose finding study assessing efficacy, pharmacokinetics, safety, and tolerability of BXCL501 with 3 dosing groups in adult (65 years and older) males and females with acute agitation associated with all forms of dementia. Evaluation of three (3) doses of sublingual BXCL 501 are planned. Cohort 1, Cohort 2 and Cohort 3 will be given 30µg, 60µg and 90µg dose respectively of BXCL501 or placebo. Subjects assigned to Cohort 3 will participate in a 1-week safety observation before being enrolled.

This is an adaptive design as doses selected for testing may be different from these, based upon safety reviews. Doses lower or higher may be chosen to test, up to 180µg, and additional subjects may be added to a cohort. BXCL501 films may be divided in half if needed to deliver half-dose strengths. At least 30 subjects (10 per cohort) will be enrolled at up to 3 study sites in the United States. In Part B a total of 46 subjects will receive BXCL501 40 μg or matching placebo film.

The effects of BXCL 501 on acute agitation will be assessed by the following scales: Pittsburgh Agitation Scale (PAS), the PANSS-EC (PEC), Cohen-Mansfield Agitation Inventory (CMAI), CGI-Severity for Agitation and CGI Improvement for Agitation. Adverse Events (AEs), clinical laboratory tests, ECG, and vital signs will be monitored, and all observed.

Inclusion Criteria:

• Male and female patients 65 years and older.
• Patients who have dementia and a history of acute agitation.
• History of agitation that requires intervention or impairs social or daily activities
• Patients who meet International Psychogeriatric Association (IPA) diagnostic criterion for agitation.
• Patients with a total score of ≥ 8 on the Pittsburgh Agitation Scale (PAS).
• Patients who have a score of ≥ 2 on at least 1 of the 4 items on the Pittsburgh Agitation Scale (PAS).
• Patients who read, understand and provide written informed consent, or who have a Legally Authorized Representative (LAR).
• Patients who are in good general health.

Exclusion Criteria:

• For Part B: Patients with dementia associated with Parkinson's disease and/or Lewy Body Disease, if etiology of dementia is known.
• Patients with agitation caused by acute intoxication.
• Patients treated within 4 hours prior to study drug administration with benzodiazepines, other sedatives, hypnotics or oral or short-acting intramuscular antipsychotics must be excluded.
• Treatment with alpha-1 noradrenergic blockers, alpha adrenergic antagonists within 8 hours prior to dosing.
• No new chronic medications initiated in the past 14 days prior to screening excluding over-the-counter products taken sporadically.
• Patients at significant risk of harm to themselves or others
• Patients considered medically unstable or in recovery
• Patients with history of clinically significant syncope or syncopal attacks, orthostatic hypotension within the past 2 years, current evidence of hypovolemia, orthostatic hypotension.
• Cohort 3 only: Patients who are taking nitrates or beta blockers shall be excluded. Any other anti-hypertensives should be maintained in the course of the study.
• Patients who have received an investigational drug within 30 days prior to the current agitation episode must be excluded.
• Patients experiencing clinically significant pain, per Investigator.
• Cohort 3 only: Patients who are a high fall risk assessed via the Johns Hopkins Fall Risk Assessment (total score >13) or during the 1-week safety observation period
• Pregnancy