Healthy ParticipantsPhase 1NCT05824143
Open-label Trial to Evaluate the Effect Carbamazepine on Darigabat Pharmacokinetics in Healthy Adult Participants
A Phase 1 study testing Darigabat and Carbamazepine in people with Healthy Participants, run by Cerevel Therapeutics, LLC at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- Darigabat and Carbamazepine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Apr 2023to 7 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female (both women of childbearing and nonchildbearing potential) participants, ages 18-55 years, inclusive, at the time of signing the informed consent form (ICF).
- Sexually active women of childbearing potential must agree to be on a non-hormonal highly effective method of contraception with low user-dependency (eg, IUD or bilateral tubal ligation) from signing of informed consent throughout the duration of the trial until the last dose of darigabat and for an additional 33 days after the last dose of darigabat.
- 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.
- Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, electrocardiogram (ECGs), vital sign measurements, and laboratory test results, as evaluated by the investigator.
- Body mass index of 18.5 to 35.0 kilograms per square meter (kg/m^2), inclusive, and total body weight ≥50 kilograms (kg) (110 pounds [lbs]) at Screening.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.
- Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.
Who cannot join
- "Yes" responses for any of the following items on the Columbia-Suicide Severity Rating Scale (C-SSRS) (within the individual's lifetime):
- Suicidal Ideation Item 3 (Active Suicidal Ideation with Any Methods [Not Plan] without Intent to Act)
- Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan)
- Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent)
- Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior) "Yes" responses for any of the following items on the C-SSRS (within past 12 months):
- Suicidal Ideation Item 1 (Wish to be Dead)
Show all 20Show fewer
- Suicidal Ideation Item 2 (Non-Specific Active Suicidal Thoughts) Serious risk of suicide in the opinion of the investigator is also exclusionary.
- 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:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > upper limit of normal (ULN)
- Total bilirubin >1.5 × ULN. If Gilbert's syndrome is suspected, total bilirubin > ULN is acceptable if the conjugated or direct bilirubin fraction is <20% of total bilirubin, and eligibility is confirmed following discussion with the medical monitor.
- 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:
- Platelets, white blood cell count, absolute neutrophil count, or hemoglobin < lower limit of normal (LLN)
- Serum sodium < LLN
- Note: Other protocol-defined exclusion criteria may apply.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label, Fixed-Sequence Trial to Evaluate the Effect of Carbamazepine on the Single-Dose Pharmacokinetics of Darigabat in Healthy Adult Participants
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.
- Conditions
- Healthy Participants
- Being tested
- Darigabat, Carbamazepine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarigabatDrug
Also called CVL-865
Oral tablet
CarbamazepineDrug
Oral tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Darigabat; Drug: Carbamazepine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax) of Darigabat
PK of darigabat will be analyzed both in the presence and absence of carbamazepine.
Measured: 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.
Measured: 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.
Measured: 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
Secondary outcomes (6)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Measured: Up to Day 52
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values
Measured: Up to Day 21
Number of Participants With Clinically Significant Changes in Vital Sign Values
Measured: Up to Day 21
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Measured: Up to Day 21
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
Measured: 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.
Measured: Up to Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2023
- Study start17 Apr 2023
- Primary completion7 Jul 2023
- Study completion7 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerevel Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05824143
- Sponsor's protocol ID
- CVL-865-HV-1003
- Status last verified
- Aug 2023
- First submitted
- 24 Mar 2023
- Last updated
- 3 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Fixed-Sequence Trial to Evaluate the Effect of Carbamazepine on the Single-Dose Pharmacokinetics of Darigabat in Healthy Adult Participants
- ClinicalTrials.gov ID
- NCT05824143
- Acronym / sponsor ID
- CVL-865-HV-1003
- Conditions
- Healthy Participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Cerevel Therapeutics, LLCIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2023 (actual)
- Primary completion
- 7 Jul 2023 (actual)
- Study completion
- 7 Jul 2023 (actual)
- First posted
- 21 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Darigabat Followed by Darigabat + Carbamazepine | Experimental | Drug: Darigabat, Drug: CarbamazepineParticipants 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male and female (both women of childbearing and nonchildbearing potential) participants, ages 18-55 years, inclusive, at the time of signing the informed consent form (ICF).
- Sexually active women of childbearing potential must agree to be on a non-hormonal highly effective method of contraception with low user-dependency (eg, IUD or bilateral tubal ligation) from signing of informed consent throughout the duration of the trial until the last dose of darigabat and for an additional 33 days after the last dose of darigabat.
- 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.
- Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, electrocardiogram (ECGs), vital sign measurements, and laboratory test results, as evaluated by the investigator.
- Body mass index of 18.5 to 35.0 kilograms per square meter (kg/m^2), inclusive, and total body weight ≥50 kilograms (kg) (110 pounds [lbs]) at Screening.
Key exclusion criteria (20 listed)
- "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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DarigabatAlso: CVL-865Oral tablet | Drug | Darigabat Followed by Darigabat + Carbamazepine |
| CarbamazepineOral tablets | Drug | Darigabat Followed by Darigabat + Carbamazepine |
Primary outcome
Maximum Observed Plasma Concentration (Cmax) of Darigabat
Time frame: 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
PK of darigabat will be analyzed both in the presence and absence of carbamazepine.
Area Under the Plasma Concentration-time Curve up to the Last Specified Sampling Time (AUC0-t) of Darigabat
Time frame: 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
PK of darigabat will be analyzed both in the presence and absence of carbamazepine.
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of Darigabat
Time frame: 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
PK of darigabat will be analyzed both in the presence and absence of carbamazepine.
6 secondary outcomes
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to Day 52
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values
Time frame: Up to Day 21
Number of Participants With Clinically Significant Changes in Vital Sign Values
Time frame: Up to Day 21
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Time frame: Up to Day 21
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
Time frame: Up to Day 21
Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Time frame: Up to Day 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Darigabat and Carbamazepine in people with Healthy Participants, run by Cerevel Therapeutics, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Observed Plasma Concentration (Cmax) of Darigabat (time frame: 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2023.