Tachyphylaxis, Tolerance, & Withdrawal Post Treatment With Igalmi for Agitation in Schizophrenia or Bipolar Disorder

• ClinicalTrials.gov Identifier: NCT06041646
• Recruitment Status: Completed
• First Posted: September 18, 2023
• Sponsor: BioXcel Therapeutics Inc
• Collaborator: Lotus Clinical Research, LLC
• Information provided by (Responsible Party): BioXcel Therapeutics Inc

Study Description

Brief Summary:

This is an in-clinic, single arm, open-label study assessing tachyphylaxis, tolerance, and withdrawal following repeated doses of Igalmi in adult males and females with agitation associated with schizophrenia or bipolar disorder.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder; Schizophrenia; Agitation,Psychomotor; Schizo Affective Disorder; Schizophreniform Disorders	Drug: Sublingual film containing Igalmi	Phase 4

Detailed Description:

This is an in-clinic, single arm, open-label study assessing tachyphylaxis, tolerance, and withdrawal following repeated doses of Igalmi in adult males and females (18 to 65 years old, inclusive) with agitation associated with schizophrenia or bipolar disorder. Subjects will be screened for eligibility within 15 days of first dose and no study procedures will occur unless subjects provide written informed consent. Subjects will receive single doses of 180 μg of Igalmi as needed for the treatment of agitation over a period of 7 days followed by a 3- day follow-up period during which time no Igalmi will be administered in an effort to characterize any potential withdrawal. Subjects will sublingually self-administer Igalmi for an agitation episode that reaches a pre-dose PEC total score of 14 or greater, as determined by a trained rater. Safety assessments will be conducted before and after each dose. If the subject's agitation is recurrent or persistent, repeat doses of 90 µg may be administered (no more than 2 repeat doses within a 24-hour period) in the absence of any safety concerns or adverse events.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-Label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Characterization of Tachyphylaxis, Tolerance, and Withdrawal After Discontinuation of Igalmi in Frequently Agitated Schizophrenic or Bipolar Patients After 7 Days of PRN Treatment
• Actual Study Start Date: October 12, 2023
• Actual Primary Completion Date: April 29, 2024
• Actual Study Completion Date: April 29, 2024

Arms and Interventions

Arm

Intervention/treatment

Active Treatment - 180 mcg of Igalmi (dexmedetomidine); An initial dose of 180 µg of Igalmi as needed for the treatment of agitation over a period of 7 days. In the event of persistent or recurrent agitation, investigators may choose to repeat dose at 90 μg after the 2-hour time point in the absence of dose-limiting adverse events or safety concerns. A maximum of 2 repeat doses will be allowed in a 24-hour period.

Drug: Sublingual film containing Igalmi; Sublingual film containing 180 µg of Igalmi (dexmedetomidine); Other Names: Dexmedetomidine; BXCL501

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score [ Time Frame: Baseline and 2 hours post-dose for all doses administered ]
   The Positive and Negative Syndrome Scale-Excited Component (PEC) includes 5 items-poor impulse control, tension, hostility, uncooperativeness, and excitement-each of which is rated from 1 (minimum) to 7 (maximum); the sum of these 5 items, the PEC total score, ranges from 5 (absence of agitation) to 35 (extremely severe).
2. Clinical Global Impression - Improvement (CGI-I) [ Time Frame: 2 hours post-dose for all doses administered ]
   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.

Secondary Outcome Measures :

1. Incidence of Adverse Events During the Follow-up Period [ Time Frame: Day 8 through Day 10 ]
   Evaluation of withdrawal phenomenon based on the occurrence of adverse events such as tachycardia, systolic hypertension, nausea, or vomiting and the emergence of any new adverse events on ≥2 consecutive days of the 3-day off-treatment follow-up period.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male and female subjects between the ages of 18 to 65 years, inclusive.
2. Subjects who have met DSM-5 criteria for schizophrenia, schizoaffective, or schizophreniform disorder or bipolar I or II disorder.
3. Subjects who are currently moderate to severely agitated at least 3 days a week.
4. Subjects who read, understand, and provide written informed consent.
5. Subjects who are in good general health prior to study participation as determined by a detailed medical history and in the opinion of the Principal Investigator.
6. Subjects who agree to use a medically acceptable and effective birth control method
7. Subjects must be willing to remain in-clinic for the duration of the study.

Exclusion Criteria:

1. Subjects with agitation caused by acute intoxication, including positive identification of alcohol by breathalyzer or drugs of abuse during screening.
2. Use of benzodiazepines or other hypnotics or antipsychotic drugs in the 6 hours before study treatment.
3. Subjects with congenital prolonged QT syndrome.
4. Prior treatment with Igalmi

Contacts and Locations

Locations

United States, Arkansas

BioXcel Clinical Research Site

Little Rock, Arkansas, United States, 72211

BioXcel Clinical Research Site

Rogers, Arkansas, United States, 72758

Sponsors and Collaborators

BioXcel Therapeutics Inc

Lotus Clinical Research, LLC

Investigators

• Study Chair: Robert Risinger, MD; BioXcel Therapeutics

More Information

• Responsible Party: BioXcel Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT06041646
• Other Study ID Numbers: BXCL501-404
• First Posted: September 18, 2023
• Last Update Posted: May 13, 2024
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioXcel Therapeutics Inc:

Agitation; Schizophrenia; Bipolar; Dexmedetomidine; tachyphylaxis; tolerance; withdrawal; PRN treatment; Open-Label; PEC; CGI; ACES; Safety; Tolerability; Igalmi

Additional relevant MeSH terms:

Psychomotor Agitation; Schizophrenia; Bipolar Disorder; Mood Disorders; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Psychomotor Disorders; Neurobehavioral Manifestations; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Dexmedetomidine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action