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Completed

NCT Number: NCT05581823

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

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.

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Madison, Wisconsin

Madison, Wisconsin, 53704, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • "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).

Serious risk of suicide in the opinion of the investigator is also exclusionary.

  • 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.

NOTE: Other protocol-defined Exclusion criteria may apply.

Treatment and study plan

Tavapadon

Drug

Oral tablets

Other names: CVL-751, PF-06649751

carbamazepine

Drug

Extended-release oral tablets

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Tavapadon

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

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

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

Secondary outcomes

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

    Time frame: Day 1 up to Day 36

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

    Time frame: Up to Day 31

  3. Number of Participants with Clinically Significant Changes in Vital Sign Values

    Time frame: Up to Day 31

  4. Number of Participants with Clinically Significant Changes in Clinical Laboratory Assessments

    Time frame: Up to Day 30

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

    Time frame: Up to Day 31

  6. Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)

    Time frame: Up to Day 31

    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.

Sponsors and collaborators

Lead sponsor

Cerevel Therapeutics, LLC

Industry

Registry information

Official study title

A Phase 1, Open-label, Fixed-sequence, Crossover Trial to Evaluate the Effects of Cytochrome P450 (CYP) 3A4 Induction by Carbamazepine on the Steady-state Pharmacokinetics of Tavapadon in Healthy Adult Participants

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Oct 17, 2022
Registry last updated
Apr 20, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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