Agitation,Psychomotor, Bipolar Disorder, Schizo Affective Disorder, Schizophrenia, Schizophreniform Disorders
Conditions
Keywords
Agitation, Schizophrenia, Bipolar, Dexmedetomidine, tachyphylaxis, tolerance, withdrawal, PRN treatment, Open-Label, PEC, CGI, ACES, Safety, Tolerability, Igalmi
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.
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.
Interventions
DRUGSublingual film containing Igalmi
Sublingual film containing 180 µg of Igalmi (dexmedetomidine)
Sponsors
BioXcel Therapeutics Inc
Lotus Clinical Research, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-Label
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Baseline and 2 hours post-dose for all doses administered over 7 days. | 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). |
| Clinical Global Impression - Improvement (CGI-I) | 2 hours post-dose for all doses administered over 7 days. | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events During the Follow-up Period | 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. |
Countries
United States
Contacts
STUDY_CHAIRBioXcel MM, MD
BioXcel Therapeutics
Participant flow
Recruitment details
The study was conducted in the United States from 02Oct2023 to 29Apr2024.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Sublingual film containing Igalmi: Sublingual film containing 180 µg of Igalmi (dexmedetomidine) | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) |
|---|---|
| Age, Continuous | 45.4 years STANDARD_DEVIATION 8.85 |
| Diagnosis Bipolar 1 or 2 | 17 Participants |
| Diagnosis Schizoaffective disorder | 2 Participants |
| Diagnosis Schizophrenia | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 14 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score
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).
Time frame: Baseline and 2 hours post-dose for all doses administered over 7 days.
Population: For each dose the population consists only of patients who took that dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 1 | -10.4 score on a scale | Standard Deviation 2.94 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 2 | -10.0 score on a scale | Standard Deviation 3.54 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 3 | -10.1 score on a scale | Standard Deviation 3.6 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 4 | -9.8 score on a scale | Standard Deviation 2.55 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 5 | -11.5 score on a scale | Standard Deviation 4.51 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 6 | -8.7 score on a scale | Standard Deviation 3.79 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Change From Baseline in the Positive and Negative Syndrome Scale- Excited Component (PEC) Total Score | Dose 7 | -11.0 score on a scale | — |
Primary
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.
Time frame: 2 hours post-dose for all doses administered over 7 days.
Population: For each dose only the patients who took that dose are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 7 | 2.0 score on a scale | — |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 1 | 1.2 score on a scale | Standard Deviation 0.5 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 2 | 1.2 score on a scale | Standard Deviation 0.39 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 3 | 1.3 score on a scale | Standard Deviation 0.47 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 4 | 1.0 score on a scale | Standard Deviation 0 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 5 | 1.2 score on a scale | Standard Deviation 0.41 |
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Clinical Global Impression - Improvement (CGI-I) | Dose 6 | 1.3 score on a scale | Standard Deviation 0.58 |
Secondary
Number of Participants With Adverse Events During the Follow-up Period
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.
Time frame: Day 8 through Day 10
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Treatment - 180 mcg of Igalmi (Dexmedetomidine) | Number of Participants With Adverse Events During the Follow-up Period | 0 Participants |