Study to Evaluate the Effects of Cytochrome P450 (CYP) 3A4 Inducer Carbamazepine on Tavapadon Pharmacokinetics in Healthy Adult Participants

NCT05581823 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-751-1005
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to evaluate the effect of carbamazepine, a strong CYP3A4 inducer, on the steady-state pharmacokinetics (PK) of tavapadon in healthy adult participants.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of Tavapadon

  Pre-dose and at multiple timepoints post-dose up to Day 31

• Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCτ) of Tavapadon

  Pre-dose and at multiple timepoints post-dose up to Day 31

Secondary Outcomes (6)

• Number of Participants With Adverse Events (AEs) and AEs by Severity

  Day 1 up to Day 36

• Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values

  Up to Day 31

• Number of Participants with Clinically Significant Changes in Vital Sign Values

  Up to Day 31

• Number of Participants with Clinically Significant Changes in Clinical Laboratory Assessments

  Up to Day 30

• Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results

  Up to Day 31

Study Arms (1)

Tavapadon Followed by Tavapadon + Carbamazepine

EXPERIMENTAL

Participants will receive oral tavapadon tablets titrated up to a steady-state dose from Day 1 to Day 14. From Day 15, participants will receive oral carbamazepine tablets titrated up to a steady-state dose along with oral tavapadon tablets, up to Day 30.

Drug: Tavapadon; Drug: Carbamazepine

Interventions

Tavapadon DRUG

Oral tablets

Also known as: CVL-751, PF-06649751

Tavapadon Followed by Tavapadon + Carbamazepine

Carbamazepine DRUG

Extended-release oral tablets

Tavapadon Followed by Tavapadon + Carbamazepine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women of nonchildbearing potential and men 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF).
• Sexually active men with a pregnant or nonpregnant partner of childbearing potential must agree to use a condom during the trial and for 90 days after the last dose of carbamazepine. In addition, male participants should not donate sperm for a minimum of 90 days following the last dose of carbamazepine.
• Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
• Body mass index of 18.5 to 32.0 kilograms per square meter (kg/m\^2), inclusive, and total body weight \>50 kg (110 pounds \[lbs\]) at Screening.
• Capable of giving signed informed consent as described in the full protocol, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• 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.

You may not qualify if:

• "Yes" responses for any of the following items on the C-SSRS (within past 6 months):
• 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) "Yes" responses for any of the following items on the C-SSRS (within past 2 years):
• Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, Preparatory Acts or Behavior).
• Participants shown to carry or be 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 (e.g., prescription and over-the-counter medications, herbal medications, vitamins, and supplements) during the trial. CYP3A4 inhibitors and inducers are prohibited from 30 days prior to signing of the ICF through the end of the trial.
• Recent monoamine oxidase inhibitors (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.
• Platelets, white blood cell count, or hemoglobin \<lower limit of normal (LLN).
• Estimated glomerular filtration rate \<90 milliliters per minute (mL/min)/1.73 m\^2, as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Madison, Wisconsin

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Carbamazepine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 17, 2022
• Study Start: October 19, 2022
• Primary Completion: January 27, 2023
• Study Completion: February 2, 2023
• Last Updated: April 20, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)