Relative Bioavailability and Food Effect Following Single Oral Dose of Darigabat Tablet Formulations in Healthy Participants

Study Overview
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Brief Summary
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This is a Phase 1, single-center trial in healthy participants. This is a crossover design, open-label treatment trial with 3 periods, 6 sequences.

Detailed Description
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The trial is an open-label, randomized, 3-period, 6-sequence, crossover design to investigate the relative bioavailability and effect of food on Darigabat.

Official Title
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A Randomized, 3-Period Crossover Trial to Evaluate the Relative Bioavailability and Food Effect Following Single Oral Dose of Darigabat Tablet Formulations in Healthy Adult Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: Darigabat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women of nonchildbearing potential and men, ages 18 to 55 years, inclusive. Healthy as determined by medical evaluation by the investigator. Body mass index of 18.5 to 30.0 kg/m2, inclusive, and a total body weight >50 kg (110 lbs). A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use contraception. Capable of giving signed informed consent and complying with study requirements. Exclusion Criteria: Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator), hematological, immunological, neurological, or psychiatric disease. Serious risk of suicide in the opinion of the investigator. History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the ICF. Any condition that could possibly affect drug absorption. Receipt of SARS-CoV2 vaccine or booster as follows: mRNA: within 14 days prior to dosing Non-mRNA: within 28 days prior to dosing Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF. Taking any prohibited medication prior to randomization or likely to require prohibited concomitant therapy. History of HIV, hepatitis B, or hepatitis C infection, or positive result for HIV, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody. Positive drug screen (including nicotine and cannabinoids) or a positive test for alcohol. Abnormal clinical laboratory test results or vital measurements at Screening. Any other abnormal safety findings unless, based on the investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a Phase 1, single-center trial in healthy participants. The trial is an open-label, randomized, 3-period, 6-sequence, crossover design to investigate the relative bioavailability and effect of food of Darigabat from a single oral.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fasted (Without Food)<br>Oral Dose | Drug: Darigabat<br>* Tablets<br>|
| Experimental: Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fed (With food)<br>Oral Dose | Drug: Darigabat<br>* Tablets<br>|
| Experimental: Single Oral Dose of 25 mg administered as 2 x 7.5 and 2 x 5.0 mg tablets, Fasted (Without Food)<br>Oral Dose | Drug: Darigabat<br>* Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose: Peak Plasma Concentrations | Peak Plasma Concentration (Cmax) for Darigabat under fasted conditions | Day 1 to Day 4 | 
| Single Dose: Area under the plasma concentration-time curve | Area under the plasma concentration-time curve (AUC) for Darigabat under fasted conditions | Day 1 to Day 4 | 
| Single Dose: Area under the plasma concentration-time curve from time zero to last concentration measured | Area under the plasma concentration-time curve from time zero to last concentration measured (AUClast) for Darigabat under fasted conditions | Day 1 to Day 4 | 
| Single Dose: Time of Maximum Observed Plasma Concentrations | Time of Maximum Observed Plasma Concentrations (Tmax) for Darigabat under fasted conditions | Day 1 to Day 4 | 
| Secondary Objective: Single Dose: Peak Plasma Concentrations | Peak Plasma Concentration (Cmax) for Darigabat under fed and fasted conditions | Day 1 to Day 4 | 
| Secondary Objective: Single Dose: Area under the plasma concentration-time curve | Area under the plasma concentration-time curve (AUC) for Darigabat under fed and fasted conditions | Day 1 to Day 4 | 
| Secondary Objective: Single Dose: Area under the plasma concentration-time curve from time zero to infinity | Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for CVL-865 under fed and fasted conditions | Day 1 to Day 4 | 
| Secondary Objective: Single Dose: Time of Maximum Observed Plasma Concentrations | Time of Maximum Observed Plasma Concentrations (Tmax) for Darigabat under fasted and fed conditions | Day 1 to Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome (AE) | Number of subjects with reported Treatment Emergent Adverse Events (TEAEs) | Day 1 to Day 4 | 
| Secondary Outcome (ECGs) | Number of subjects with clinically significant changes in Electrocardiograms. | Day 1 to Day 4 | 
| Secondary Outcome (Labs) | Number of subjects with clinically significant changes in laboratory measures. | Day 1 to Day 4 | 
| Secondary Outcome (Vital Signs) | Number of subjects with clinically meaningful changes in vitals signs. | Day 1 to Day 4 | 
| Secondary Outcome (Physical/Neurological Exam) | Number of subjects with clinically significant changes in physical and neurological exams. | Day 1 to Day 4 | 
| Secondary Outcome (C-SSRS) | Changes from baseline of the Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent. The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). | Day 1 to Day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteer, Bioavailability, Food effect