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The primary purpose of the study is to evaluate the effect of increased metabolizing enzyme (cytochrome P450 [CYP] 3A4) due to carbamazepine, a strong CYP3A4 inducer, on the pharmacokinetics (PK) of darigabat in healthy adult participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Darigabat Followed by Darigabat + Carbamazepine | Experimental | Participants will receive darigabat tablet orally once on Day 1 of Treatment Period 1. Participants will receive carbamazepine tablets, titrated up to a steady-state dose, orally, twice daily (BID) from Day 1 to 17 along with the darigabat tablet orally once on Day 16 of Treatment Period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darigabat | Drug | Oral tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Darigabat | PK of darigabat will be analyzed both in the presence and absence of carbamazepine. | Treatment Period 1: 15 minutes pre-dose on Day 1 and up to 48 hours post dose; Treatment Period 2: 15 minutes pre-dose on Day 16 and up to 48 hours post dose |
| Area Under the Plasma Concentration-time Curve up to the Last Specified Sampling Time (AUC0-t) of Darigabat | PK of darigabat will be analyzed both in the presence and absence of carbamazepine. | Treatment Period 1: 15 minutes pre-dose on Day 1 and up to 48 hours post dose; Treatment Period 2: 15 minutes pre-dose on Day 16 and up to 48 hours post dose |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Darigabat | PK of darigabat will be analyzed both in the presence and absence of carbamazepine. | Treatment Period 1: 15 minutes pre-dose on Day 1 and up to 48 hours post dose; Treatment Period 2: 15 minutes pre-dose on Day 16 and up to 48 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to Day 52 | |
| Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values | Up to Day 21 | |
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Inclusion Criteria:
A male participant who is sexually active with a pregnant or a nonpregnant partner of childbearing potential must agree to use a condom during treatment and until the last dose of darigabat plus an additional 93 days. In addition, male participants should not donate sperm for a minimum of 93 days following last dose of darigabat.
Exclusion Criteria:
"Yes" responses for any of the following items on the Columbia-Suicide Severity Rating Scale (C-SSRS) (within the individual's lifetime):
Any condition or surgery that could possibly affect drug absorption, including, but not limited to, bowel resections, bariatric weight loss surgery/procedures, gastrectomy, and cholecystectomy.
Known allergy or hypersensitivity to the investigational medicinal product (IMP), including carbamazepine, closely related compounds, or any of their specified ingredients.
Participants positive for human leukocyte antigen (HLA)-B 1502 or HLA-A 3101.
Use of prohibited medication prior to randomization (5 half-lives) or likely to require prohibited concomitant therapy during the trial. CYP3A4 inhibitors and inducers are prohibited from 30 days prior to signing of the ICF through the end of the trial. Vaccinations or boosters within 7 days of planned dosing or while on trial are prohibited.
Recent monoamine oxidase (MAO)-I use (in the last 28 days), as it increases the risk for hypersensitivity and bone marrow suppression from carbamazepine.
Prior carbamazepine use that was discontinued for tolerability or adverse events, including a clinically significant decrease in platelets, white blood cells, or hemoglobin.
Any of the following clinical laboratory test results at the Screening Visit or Check-in (Day -1), which can be confirmed by a single repeat measurement:
Any of the following clinical laboratory test results at the Screening Visit or Check-in (Day -1), which can be confirmed by a single repeat measurement:
Note: Other protocol-defined exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando, Florida | Orlando | Florida | 32806 | United States |
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| ID | Term |
|---|---|
| D002220 | Carbamazepine |
| ID | Term |
|---|---|
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Carbamazepine | Drug | Oral tablets |
|
| Number of Participants With Clinically Significant Changes in Vital Sign Values |
| Up to Day 21 |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | Up to Day 21 |
| Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Up to Day 21 |
| Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk. | Up to Day 21 |