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

Sponsor

BioXcel Therapeutics Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05658510

Collaborator

Worldwide Clinical Trials (Other)

450

Enrollment

Locations

Arms

16.3

Anticipated Duration (Months)

26.5

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this study, an investigational medication named BXCL501 is being tested for the treatment of episodes of agitation associated with bipolar I and bipolar II disorder, schizophrenia, schizoaffective and schizophreniform disorder. This study compares the study drug to a placebo.

Condition or Disease	Intervention/Treatment	Phase
Agitation,Psychomotor Bipolar I Disorder Bipolar II Disorder Schizophrenia Schizoaffective Disorder Schizophreniform Disorders	Drug: BXCL501 Drug: Matching Placebo	Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled, 2-Part, Phase III study to assess the efficacy, safety, and tolerability of a 60 mcg dose 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, and post-treatment observation period with patients experiencing an acute episode of agitation. Part 2 of the study is a 12-week study to determine the safety of BXCL501 when used as needed for episodes of agitation at home.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients randomized to receive 60 mcg of BXCL501 or a matching placebo.Patients randomized to receive 60 mcg of BXCL501 or a matching placebo.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Efficacy And Safety of BXCL501 Evaluated For At-Home Use In A Multisite Double-Blind Placebo-Controlled Trial For Agitation Associated With Schizophrenia And Bipolar Disorder

Actual Study Start Date :

Nov 21, 2022

Anticipated Primary Completion Date :

Mar 30, 2024

Anticipated Study Completion Date :

Mar 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: 60 mcg of BXCL501 Sublingual film containing 60 Micrograms Dexmedetomidine	Drug: BXCL501 Sublingual Film Other Names: Dexmedetomidine
Placebo Comparator: Part 1: Matching Placebo Sublingual Placebo film	Drug: Matching Placebo Sublingual Placebo Film Other Names: Placebo
Experimental: Part 2: 60 mcg of BXCL501 Sublingual film containing 60 Micrograms Dexmedetomidine	Drug: BXCL501 Sublingual Film Other Names: Dexmedetomidine
Placebo Comparator: Part 2: Matching Placebo Sublingual Placebo film	Drug: Matching Placebo Sublingual Placebo Film Other Names: Placebo

Outcome Measures

Primary Outcome Measures

Part 1: Change from baseline in Positive and Negative Syndrome Scale - Excited (PEC) total score [2 hours]
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)
Part 2: Incidence of treatment-emergent adverse events (TEAEs) [Through study completion, an average of 12 weeks]
To assess the safety of BXCL501 when used at-home based on treatment-emergent adverse events (TEAEs)
Part 2: Incidence of serious adverse events (SAEs) [Through study completion, an average of 12 weeks]
To assess the safety of BXCL501 when used at-home based on serious adverse events (SAEs)

Secondary Outcome Measures

Part 1: Clinical Global Impression - Improvement (CGI-I) [2 hours]
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.
Part 1: Change in Modified Clinical Global Impression - Severity (mCGI-S) scores from Baseline [2 hours]
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).
Part 1:The number of responders based on the Modified Clinical Global Impression - Severity (mCGI-S) score [2 hours]
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)
Part 1:Change from baseline in Agitation-Calmness Evaluation Scale (ACES) [2 hours]
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.
Part 1: Incidence of treatment-emergent adverse events (TEAEs) [Through study completion, an average of 8 hours]
To assess the safety of BXCL501 based on treatment-emergent adverse events (TEAEs)
Part 1: Change from baseline in heart rate (HR) at rest [Baseline, and 2, 4, 6, and 8 hours postdose]
The effect of BXCL501 on heart rate at rest
Part 1: Change from baseline in heart rate (HR) under orthostatic stress [Baseline, and 2, 4, 6, and 8 hours postdose]
The effect of BXCL501 on heart rate under orthostatic stress
Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at rest [Baseline, and 2, 4, 6, and 8 hours postdose]
The effect of BXCL501 on systolic and diastolic blood pressure at rest
Part 1: Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) under orthostatic stress [Baseline, and 2, 4, 6, and 8 hours postdose]
The effect of BXCL501 on systolic and diastolic blood pressure under orthostatic stress
Part 1: Incidence of abnormal electrocardiograms (ECG) reported as an adverse event (AE) [Through study completion, an average of 8 hours]
Any abnormal ECG value that is reported as an adverse event (AE)
Part 1: Incidence of abnormal clinical laboratory values reported as an adverse event (AE) [Through study completion, an average of 8 hours]
Any abnormal clinical laboratory value that is reported as an adverse event (AE)
Part 2: Change from baseline in Modified Clinical Global Impression - Severity (mCGI-S) [2 hours]
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).
Part 2: The number of responders based on the Modified Clinical Global Impression - Severity (mCGI-S) score [2 hours]
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)
Part 2: Number and frequency of agitation episodes [Through study completion, an average of 12 weeks]
The absolute number and frequency of reported agitation episodes will be analyzed descriptively
Part 2: Percentage of all treated episodes of agitation satisfying the definition of m-CGI-S responder [2 hours after each treatment for an episode of agitation]
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)
Part 2: Number of interactions with emergency services related to agitation episodes [Through study completion, an average of 12 weeks]
The number of reported interactions with emergency services (specifically hospitalization, emergency room visits, urgent care clinic visits, and law enforcement intervention) due to episodes of agitation will be analyzed descriptively

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

A patient may enroll in only one part of the study; either Part 1 or Part 2.

Inclusion Criteria:

Male and female patients between the ages of 18 to 75 years, inclusive
Patients who can read, understand and provide written informed consent.
Patients who have met Diagnostic and Statistical Manual5/5-Text Revision criteria for bipolar I or bipolar II disorder, schizophrenia, schizoaffective or schizophreniform disorder.
Patients who, in the opinion of the Principal Investigator, are in good general health before study participation based on a detailed medical history, a physical examination, a 12-lead ECG, a blood chemistry profile, hematology, and urinalysis.
Participants who agree to use a medically acceptable and effective birth control method

Part 1 only

Patients who are judged to be clinically agitated at Screening and Baseline with a total score of ≥ 14 on the 5 items (poor impulse control, tension, hostility, uncooperativeness, and excitement) comprising the PEC.
Patients with a score of ≥4 on at least 1 of the 5 items on the PEC at Baseline.

Part 2 only

Patients have had at least one clinical presentation of agitation requiring an intervention in the past month
The patient has an Informant who can read, understand, and provide written informed consent and understand and follow the study procedures

Exclusion Criteria:

Patients with serious or unstable medical illnesses.
A history of agitation episodes due to substance use.
A diagnosis of antisocial personality disorder, borderline personality disorder, or narcissistic personality disorder that predated the diagnosis of schizophrenia or bipolar disorder
Patients who are judged to be at significant risk of suicide
Female patients who have a positive pregnancy test at Screening or Baseline, or are breastfeeding.
Patients currently treated with alpha-1 noradrenergic blockers (terazosin, doxazosin, tamsulosin, alfuzosin, or prazosin), alpha-2 adrenergic agonists, or other prohibited medications.
Patients with hydrocephalus, seizure disorder, or history of significant head trauma, stroke, transient ischemic attack, subarachnoid bleeding, brain tumor, encephalopathy, meningitis, Parkinson's disease, or focal neurological findings.
History of syncope or other syncopal attacks, current evidence of hypovolemia, or orthostatic hypotension
Patients with laboratory or ECG abnormalities considered clinically significant by the Investigator
Patients who have received an investigational drug within 30 days before the study start
Patients who have previously received BXCL501 in either a clinical trial or via prescription
Patients considered by the Investigator to be unsuitable candidates for receiving dexmedetomidine or considered to be unsuitable for participating in the study for any reason.

Part 1 only

Patients with agitation caused by acute intoxication, including identification of alcohol by breathalyzer or drugs of abuse (except for THC) during urine screening.
Use of benzodiazepines or other hypnotics or antipsychotic drugs in the 4 hours before study treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BioXcel Clinical Research Site	Little Rock	Arkansas	United States	72211
2	BioXcel Clinical Research Site	Bellflower	California	United States	90706
3	BioXcel Clinical Research Site	Culver City	California	United States	90230
4	BioXcel Clinical Research Site	Garden Grove	California	United States	92845
5	BioXcel Clinical Research Site	Lemon Grove	California	United States	91945
6	BioXcel Clinical Research Site	Los Angeles	California	United States	90015
7	BioXcel Clinical Research Site	Orange	California	United States	92868
8	BioXcel Clinical Research Site	Riverside	California	United States	92506
9	BioXcel Clinical Research Site	Santa Ana	California	United States	92705
10	BioXcel Clinical Research Site	Miami Lakes	Florida	United States	33016
11	Bioxcel Clinical Research Site	Atlanta	Georgia	United States	30331
12	BioXcel Clinical Research Site	Decatur	Georgia	United States	30030
13	BioXcel Clinical Research Site	Chicago	Illinois	United States	60640
14	BioXcel Clinical Research Site	Gaithersburg	Maryland	United States	20877
15	BioXcel Clinical Research Site	Berlin	New Jersey	United States	08009
16	BioXcel Clinical Research Site	Marlton	New Jersey	United States	08053
17	BioXcel Clinical Research Site	DeSoto	Texas	United States	75115