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

Parkinson Disease Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05581823
• Other study ID #: CVL-751-1005
• Status: Completed
• Phase: Phase 1
• Start date: October 19, 2022
• Est. completion date: February 2, 2023

Study information

• Verified date: April 2023
• Source: Cerevel Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 2, 2023
• Est. primary completion date: January 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Women of nonchildbearing potential and men 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF).

2. 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.

3. 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.

4. 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.

5. 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.

6. 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:

1. "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.

2. Participants shown to carry or be positive for human leukocyte antigen (HLA)-B*1502 or HLA-A*3101.

3. 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.

4. 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.

5. Prior carbamazepine use that was discontinued for tolerability or adverse events, including a clinically significant decrease in platelets, white blood cells or hemoglobin.

6. Platelets, white blood cell count, or hemoglobin <lower limit of normal (LLN).

7. 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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Tavapadon
Oral tablets
• Carbamazepine
Extended-release oral tablets

Locations

Country	Name	City	State
United States	Madison, Wisconsin	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Cerevel Therapeutics, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 31
Primary	Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCt) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 31
Secondary	Number of Participants With Adverse Events (AEs) and AEs by Severity		Day 1 up to Day 36
Secondary	Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values		Up to Day 31
Secondary	Number of Participants with Clinically Significant Changes in Vital Sign Values		Up to Day 31
Secondary	Number of Participants with Clinically Significant Changes in Clinical Laboratory Assessments		Up to Day 30
Secondary	Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results		Up to Day 31
Secondary	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.	Up to Day 31