Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia and Bipolar Disorder (SERENITY III)

This is a randomized, double-blind, placebo-controlled, 2-Part, Phase III study to assess the efficacy, safety, and tolerability of BXCL501 in adult (18-75 years old) males and females with agitation episodes associated with a primary diagnosis of bipolar I disorder, bipolar II disorder, schizophrenia, schizoaffective disorder, or schizophreniform disorder. Part 1 of the study is a one-day, in-clinic treatment of 60 mcg dose, and post-treatment observation period with patients experiencing an acute episode of agitation. Part 1 is now complete. Part 2 of the study is a 12-week study to determine the safety of a BXCL501 120 mcg dose when used as needed for episodes of agitation at home.

Primary Outcome Measures

1. Part 1: Change from baseline in Positive and Negative Syndrome Scale - Excited (PEC) total score
   The Positive and Negative Syndrome Scale - Excited Component (PEC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (minimum) to 7 (maximum). The PEC, the sum of these 5 subscales, thus ranges from 5 (absence of agitation) to 35 (extremely severe)
2. Part 2: The incidence of SAEs and TEAEs compared with placebo.
   To assess the safety of 120 mcg BXCL501 when used in an at-home environment based on serious adverse events (SAE) and treatment emergent adverse events (TEAEs).

Secondary Outcome Measures

1. Part 1: Clinical Global Impression - Improvement (CGI-I)
   The Clinical Global Impression - Improvement (CGI-I) for agitation in response to treatment measures the current level of agitation relative to the level of agitation prior to administration of study intervention. The CGI-I scores range from 1 to 7 with a score of 1 indicating very much improved, and a score of 7 indicating very much worse.
2. Part 1: Change in Modified Clinical Global Impression - Severity (mCGI-S) scores from Baseline
   The Modified Clinical Global Impression - Severity (mCGI-S) measures the current level of agitation. For this study, the mCGI-S is a 4-point scale where a score of 0 represents no agitation, and scores of 1-3 describe increasing severities of agitation (mild, moderate, severe).
3. Part 1:The number of responders based on the Modified Clinical Global Impression - Severity (mCGI-S) score
   The Modified Clinical Global Impression - Severity (mCGI-S) measures the current level of agitation. A responder is characterized as a participant with a score of 0 (represents no agitation) or 1 (mild agitation)
4. Part 1:Change from baseline in Agitation-Calmness Evaluation Scale (ACES)
   The Agitation-Calmness Evaluation Scale (ACES) is a single item scale that measures overall agitation and sedation, where a score of 1 indicates marked agitation; 2 - moderate agitation; 3 - mild agitation; 4 - normal behavior; 5 - mild calmness; 6 - moderate calmness; 7 - marked calmness; 8 - deep sleep; and 9 - unarousable.
5. Part 1: Incidence of treatment-emergent adverse events (TEAEs)
   To assess the safety of BXCL501 based on treatment-emergent adverse events (TEAEs)
6. Part 1: Change from baseline in heart rate (HR) at rest
   The effect of BXCL501 on heart rate at rest
7. Part 1: Change from baseline in heart rate (HR) under orthostatic stress
   The effect of BXCL501 on heart rate under orthostatic stress
8. Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at rest
   The effect of BXCL501 on systolic and diastolic blood pressure at rest
9. Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) under orthostatic stress
   The effect of BXCL501 on systolic and diastolic blood pressure under orthostatic stress
10. Part 1: Incidence of abnormal electrocardiograms (ECG) reported as an adverse event (AE)
    Any abnormal ECG value that is reported as an adverse event (AE)
11. Part 1: Incidence of abnormal clinical laboratory values reported as an adverse event (AE)
    Any abnormal clinical laboratory value that is reported as an adverse event (AE)
12. Part 2: Incidence of interactions with emergency services related to agitation
    Evaluate the impact of BXCL501 on the use of healthcare and emergency service resources because of agitation episodes
13. Part 2: Incidence of overall adverse events and AEs leading to discontinuation
    To evaluate the safety and tolerability profile of 120 mcg BXCL501