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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Darigabat

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Women of nonchildbearing potential and men, ages 18 to 55 years, inclusive.
2. Healthy as determined by medical evaluation by the investigator.
3. Body mass index of 18.5 to 30.0 kg/m2, inclusive, and a total body weight >50 kg (110 lbs).
4. A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use contraception.
5. Capable of giving signed informed consent and complying with study requirements.

Exclusion Criteria:

1. 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.
2. Serious risk of suicide in the opinion of the investigator.
3. History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the ICF.
4. Any condition that could possibly affect drug absorption.

5. Receipt of SARS-CoV2 vaccine or booster as follows:

   • mRNA: within 14 days prior to dosing
   • Non-mRNA: within 28 days prior to dosing
6. Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF.
7. Taking any prohibited medication prior to randomization or likely to require prohibited concomitant therapy.
8. 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.
9. Positive drug screen (including nicotine and cannabinoids) or a positive test for alcohol.
10. Abnormal clinical laboratory test results or vital measurements at Screening.
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

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); Oral Dose	Drug: Darigabat; Tablets
Experimental: Single Oral Dose of 25 mg administered as 1 x 25 mg tablet, Fed (With food); Oral Dose	Drug: Darigabat; Tablets
Experimental: Single Oral Dose of 25 mg administered as 2 x 7.5 and 2 x 5.0 mg tablets, Fasted (Without Food); Oral Dose	Drug: Darigabat; Tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC
• Investigators: Study Director: Ann M Dandurand, MD, Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): November 21, 2021
• Study Completion (Actual): December 7, 2021

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Volunteer; Food effect; Bioavailability
• Other Study ID Numbers: CVL-865-1002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No