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

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05658510
• Other study ID #: BXCL501-401
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 21, 2022
• Est. completion date: March 30, 2025

Study information

• Verified date: December 2023
• Source: BioXcel Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: March 30, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 three clinical presentations of agitation requiring an intervention in the past three months prior to Screening
• Patients who are receiving stable treatment for the last 3 months prior to Screening for the underlying primary diagnosis and who are expected to remain on stable treatment for the duration of the study
• Patients who manage agitation episodes with as needed (PRN) medication
• 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 via prescription (under the trade name IGALMI™) or received BXCL501 in an open-label clinical trial
• 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.
• Patients who have previously received BXCL501 in a clinical trial

Related Conditions & MeSH terms

• Agitation,Psychomotor
• Bipolar Disorder
• Bipolar I Disorder
• Bipolar II Disorder
• Psychomotor Agitation
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophreniform Disorders

Intervention

Drug:
• BXCL501
Sublingual Film
• Matching Placebo
Sublingual Placebo Film

Locations

Country	Name	City	State
United States	Bioxcel Clinical Research Site 106	Atlanta	Georgia
United States	BioXcel Clinical Research Site 122	Beachwood	Ohio
United States	BioXcel Clinical Research Site 113	Bellflower	California
United States	BioXcel Clinical Research Site 105	Berlin	New Jersey
United States	BioXcel Clinical Research Site 128	Cerritos	California
United States	BioXcel Clinical Research Site 109	Chicago	Illinois
United States	BioXcel Clinical Research Site 110	Culver City	California
United States	BioXcel Clinical Research Site 107	Decatur	Georgia
United States	BioXcel Clinical Research Site 129	Denver	Colorado
United States	BioXcel Clinical Research Site 102	DeSoto	Texas
United States	BioXcel Clinical Research Site 130	Elgin	Illinois
United States	BioXcel Clinical Research Site 126	Everett	Washington
United States	BioXcel Clinical Research Site 103	Gaithersburg	Maryland
United States	BioXcel Clinical Research Site 108	Garden Grove	California
United States	BioXcel Clinical Research Site 125	Irving	Texas
United States	BioXcel Clinical Research Site 118	Las Vegas	Nevada
United States	BioXcel Clinical Research Site 117	Lemon Grove	California
United States	BioXcel Clinical Research Site 112	Little Rock	Arkansas
United States	BioXcel Clinical Research Site 119	Little Rock	Arkansas
United States	BioXcel Clinical Research Site 121	Los Angeles	California
United States	BioXcel Clinical Research Site 101	Marlton	New Jersey
United States	BioXcel Clinical Research Site 124	Miami	Florida
United States	BioXcel Clinical Research Site 131	Miami	Florida
United States	BioXcel Clinical Research Site 120	Murray	Utah
United States	BioXcel Clinical Research Site 134	Oakland Park	Florida
United States	BioXcel Clinical Research Site 123	Oceanside	California
United States	BioXcel Clinical Research Site 104	Orange	California
United States	BioXcel Clinical Research Site 127	Plano	Texas
United States	BioXcel Clinical Research Site 133	Rancho Cucamonga	California
United States	BioXcel Clinical Research Site 114	Riverside	California
United States	BioXcel Clinical Research Site 132	Rutland	Vermont

Sponsors (2)

Lead Sponsor	Collaborator
BioXcel Therapeutics Inc	Worldwide Clinical Trials

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 hours
Primary	Part 2: Incidence of treatment-emergent adverse events (TEAEs)	To assess the safety of BXCL501 when used in an at-home environment based on treatment-emergent adverse events (TEAEs)	Through study completion, an average of 12 weeks
Primary	Part 2: Incidence of serious adverse events (SAEs)	To assess the safety of BXCL501 when used in an at-home environment based on serious adverse events (SAEs)	Through study completion, an average of 12 weeks
Secondary	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 hours
Secondary	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).	2 hours
Secondary	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)	2 hours
Secondary	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.	2 hours
Secondary	Part 1: Incidence of treatment-emergent adverse events (TEAEs)	To assess the safety of BXCL501 based on treatment-emergent adverse events (TEAEs)	Through study completion, an average of 8 hours
Secondary	Part 1: Change from baseline in heart rate (HR) at rest	The effect of BXCL501 on heart rate at rest	Baseline, and 2, 4, 6, and 8 hours postdose
Secondary	Part 1: Change from baseline in heart rate (HR) under orthostatic stress	The effect of BXCL501 on heart rate under orthostatic stress	Baseline, and 2, 4, 6, and 8 hours postdose
Secondary	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	Baseline, and 2, 4, 6, and 8 hours postdose
Secondary	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	Baseline, and 2, 4, 6, and 8 hours postdose
Secondary	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)	Through study completion, an average of 8 hours
Secondary	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)	Through study completion, an average of 8 hours
Secondary	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	Through study completion, an average of 12 weeks
Secondary	Part 2: Incidence of overall adverse events and AEs leading to discontinuation	To evaluate the safety and tolerability profile of BXCL501	Through study completion, an average of 12 weeks
Secondary	Part 2: Proportion of patients who report somnolence (ACES score =8 reported by Informant) pre-dose to post-dose	To evaluate the safety and tolerability profile of BXCL501	2 hours after each treatment for an episode of agitation
Secondary	Part 2: Proportion of patients who report somnolence (KSS score =8 reported by patient) pre-dose to post-dose	To evaluate the safety and tolerability profile of BXCL501	2 hours after each treatment for an episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	Proportion of patients with an improvement in agitation (Yes/No) post-dose for the first treated episode compared with placebo	2 hours after treatment for the first episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	Proportion of mCGI-S responders (patients who achieve a mCGI-S score of 0 or 1) following drug administration for the first treated episode	2 hours after treatment for the first episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	Proportion of patients with a 1-point improvement in mCGI-S score following drug administration for the first treated episode	2 hours after treatment for the first episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	Proportion of CGI-C responders (patients who achieve a CGI-C score of 1 or 2) following drug administration for the first treated episode	2 hours after treatment for the first episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	Change in mCGI-S scores from pre-dose to post dose for the first treated episode	2 hours after treatment for the first episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	CGI-C scores following drug administration for the first treated episode	2 hours after treatment for the first episode of agitation
Secondary	Part 2: Evaluate the effect of BXCL501 on the signs and symptoms of agitation following study drug administration in patients with schizophrenia and bipolar disorder	Time to end of an agitation episode from dosing for the first treated episode	Up to 24 hours after treatment for the first episode of agitation
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Proportion of patients with an improvement in agitation (Yes/No) post-dose for all treated episodes compared with placebo	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Proportion of mCGI-S responders following drug administration for the last treated episode and all treated episodes	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Proportion of patients with a 1-point improvement in mCGI-S score following drug administration for the last treated episode and all treated episodes	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Proportion of CGI-C responders following drug administration for the last treated episode and all treated episodes	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Change in mCGI-S scores from pre dose to post dose following drug administration for the last treated episode and all treated episodes	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	CGI-C scores following drug administration for the last treated episode and all treated episodes	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	The frequency of treated agitation episodes compared with placebo	Through study completion, an average of 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Time to end of an agitation episode from dosing for the last treated episode and across all treated episodes	Up to 24 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Assess the continued efficacy of BXCL501 in the treatment of episodes of agitation	Change in agitation behaviors scale following drug administration	2 hours after treatment for all episodes of agitation, up to 12 weeks
Secondary	Part 2: Determine the overall clinical improvement after drug administration as measured by the use of rescue medications	Proportion of patients who receive rescue medication compared with placebo	Through study completion, an average of 12 weeks
Secondary	Part 2: Determine the overall clinical improvement after drug administration as measured by the use of rescue medications	Time to use of rescue medication for patients receiving BXCL501 compared with placebo	Through study completion, an average of 12 weeks