Multiple-dose Trial to Determine the Clinical Bioequivalence Between Tavapadon Tablets in Participants With Parkinson's Disease

A Phase 1, Randomized, Multiple-dose, Crossover Trial in Participants With Parkinson's Disease to Evaluate the Clinical Bioequivalence Between Tavapadon Tablets

The primary purpose of the study is to evaluate the bioequivalence (BE) of tavapadon 15 milligram (mg) tablet to 3x5 mg tablets in participants with Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Tavapadon

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Alamitos, California, United States, 90720
      • Los Alamitos, California
  • Florida
    • Hollywood, Florida, United States, 33024
      • Hollywood, Florida
    • Orlando, Florida, United States, 32806
      • Orlando, Florida
    • South Miami, Florida, United States, 33143
      • South Miami, Florida
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Decatur, Georgia
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Farmington Hills, Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Body mass index of 17.5 to 38.0 kilograms per square meter (kg/m^2), inclusive, and total body weight >50 kg (110 pounds [lb]) at Screening.
2. Participants with a diagnosis of Parkinson's disease (PD) that is consistent with the United Kingdom (UK) Parkinson's Disease Society Brain Bank diagnostic criteria.
3. Must be modified Hoehn & Yahr Stage I-III inclusive.
4. Must be on a stable dose of L-Dopa of at least 300 mg daily in conjunction with a dopa-decarboxylase inhibitor (e.g., L-Dopa/carbidopa, L Dopa/carbidopa/entacapone or L-Dopa/benserazide) administered at least 3 times per day for at least 2 weeks prior to the Day 1 Visit.

Exclusion Criteria:

1. Participants with a history or clinical features consistent with essential tremor, atypical or secondary parkinsonian syndrome (including, but not limited to, progressive supranuclear palsy, multiple system atrophy, cortico-basal degeneration, or drug-induced or poststroke parkinsonism).
2. Participants with a history of psychosis or hallucinations within the previous 12 months.
3. Participants with epilepsy, or history of epilepsy, or conditions that lower seizure threshold, seizures of any etiology (including substance or drug withdrawal), or who have increased risk of seizures as evidenced by history of electroencephalogram with epileptiform activity are excluded. Participants with a history of febrile seizures only are allowed with medical monitor approval.
4. History of substance or alcohol-use disorder (excluding nicotine; Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria) within 2 years prior to signing the informed consent form (ICF).
5. Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this C-SSRS Item 5 occurred within the last 6 months OR Participants who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR Participants who, in the opinion of the investigator, present a serious risk of suicide.
6. Participants who have attempted suicide in the past.
7. Positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody with detectable viral ribonucleic acid (RNA) levels at Screening.
8. Have been diagnosed with symptomatic coronavirus disease (COVID-19) or test positive (i.e., using polymerase chain reaction [PCR] or rapid antigen test) for COVID-19 within 30 days prior to signing the ICF.
9. Participants taking strong or moderate cytochrome P450 family 3 subfamily A member 4 (CYP3A4) inducers or inhibitors or who would be likely to require concomitant therapy with CYP3A4 inducers or inhibitors during the trial.

NOTE: Other protocol-defined inclusion and exclusion criteria may apply.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Tavapadon 1x15 mg Followed by 3x5 mg; Participants will receive tavapadon 1x15 mg tablet, orally, once daily (QD) from Day 15 to 21. Participants will receive tavapadon 3x5 mg tablets, orally, QD from Day 22 to 28.	Drug: Tavapadon; Oral tablets; Other Names: PF-06649751; CVL-751
Experimental: Cohort 2: Tavapadon 3x5 mg Followed by 1x15 mg; Participants will receive tavapadon 3x5 mg tablets, orally, QD from Day 15 to 21. Participants will receive tavapadon 1x15 mg tablet, orally, QD from Day 22 to 28.	Drug: Tavapadon; Oral tablets; Other Names: PF-06649751; CVL-751

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Tavapadon	Pre-dose and at multiple timepoints post-dose up to Day 28
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 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Steady-state Plasma Concentration (Cmin,ss) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Average Steady-state Plasma Concentration (Cavg,ss) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Trough Concentration (Ctrough) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Time of Maximum Observed Concentration (Tmax) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Degree of Fluctuation [(Cmax - Cmin)/Cavg,ss] of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Peak-to-Trough Ratio (PTR) of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Swing [(Cmax - Cmin)/Cmin,ss] of Tavapadon		Pre-dose and at multiple timepoints post-dose up to Day 28
Apparent Clearance of Tavapadon From Plasma (CL/F)		Pre-dose and at multiple timepoints post-dose up to Day 28
Number of Participants With Adverse Events (AEs) and AEs by Severity		Up to Day 36
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values		Up to Day 29
Number of Participants With Clinically Significant Changes in Vital Sign Values		Up to Day 29
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments		Up to Day 29
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results		Up to Day 29
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 29

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Actual): December 12, 2023
• Study Completion (Actual): December 17, 2023

Study Registration Dates

• First Submitted: November 2, 2022
• First Submitted That Met QC Criteria: November 2, 2022
• First Posted (Actual): November 9, 2022

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Movement Disorders; Central Nervous System Diseases; Dopamine Agonist; Neurodegenerative Diseases; Brain Diseases; Parkinsonian Disorders; Dopamine Therapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: CVL-751-1006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No