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

Primary Purpose

Parkinson Disease

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tavapadon
Sponsored by
Cerevel Therapeutics, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinsonian Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases, Dopamine Agonist, Dopamine Therapy

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. 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. Must be modified Hoehn & Yahr Stage I-III inclusive. 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: 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). Participants with a history of psychosis or hallucinations within the previous 12 months. 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. 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). 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. Participants who have attempted suicide in the past. 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. 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. 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.

Sites / Locations

  • Los Alamitos, CaliforniaRecruiting
  • Hollywood, FloridaRecruiting
  • Orlando, FloridaRecruiting
  • South Miami, FloridaRecruiting
  • Decatur, GeorgiaRecruiting
  • Farmington Hills, MichiganRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1: Tavapadon 1x15 mg Followed by 3x5 mg

Cohort 2: Tavapadon 3x5 mg Followed by 1x15 mg

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Minimum Steady-state Plasma Concentration (Cmin,ss) of Tavapadon
Average Steady-state Plasma Concentration (Cavg,ss) of Tavapadon
Trough Concentration (Ctrough) of Tavapadon
Time of Maximum Observed Concentration (Tmax) of Tavapadon
Degree of Fluctuation [(Cmax - Cmin)/Cavg,ss] of Tavapadon
Peak-to-Trough Ratio (PTR) of Tavapadon
Swing [(Cmax - Cmin)/Cmin,ss] of Tavapadon
Apparent Clearance of Tavapadon From Plasma (CL/F)
Number of Participants With Adverse Events (AEs) and AEs by Severity
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values
Number of Participants With Clinically Significant Changes in Vital Sign Values
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
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.

Full Information

First Posted
November 2, 2022
Last Updated
October 11, 2023
Sponsor
Cerevel Therapeutics, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05610189
Brief Title
Multiple-dose Trial to Determine the Clinical Bioequivalence Between Tavapadon Tablets in Participants With Parkinson's Disease
Official Title
A Phase 1, Randomized, Multiple-dose, Crossover Trial in Participants With Parkinson's Disease to Evaluate the Clinical Bioequivalence Between Tavapadon Tablets
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2022 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
November 5, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerevel Therapeutics, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
Parkinsonian Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases, Dopamine Agonist, Dopamine Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Tavapadon 1x15 mg Followed by 3x5 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: Tavapadon 3x5 mg Followed by 1x15 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tavapadon
Other Intervention Name(s)
CVL-751, PF-06649751
Intervention Description
Oral tablets
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
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 28
Secondary Outcome Measure Information:
Title
Minimum Steady-state Plasma Concentration (Cmin,ss) of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Average Steady-state Plasma Concentration (Cavg,ss) of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Trough Concentration (Ctrough) of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Time of Maximum Observed Concentration (Tmax) of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Degree of Fluctuation [(Cmax - Cmin)/Cavg,ss] of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Peak-to-Trough Ratio (PTR) of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Swing [(Cmax - Cmin)/Cmin,ss] of Tavapadon
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Apparent Clearance of Tavapadon From Plasma (CL/F)
Time Frame
Pre-dose and at multiple timepoints post-dose up to Day 28
Title
Number of Participants With Adverse Events (AEs) and AEs by Severity
Time Frame
Up to Day 36
Title
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values
Time Frame
Up to Day 29
Title
Number of Participants With Clinically Significant Changes in Vital Sign Values
Time Frame
Up to Day 29
Title
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Time Frame
Up to Day 29
Title
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
Time Frame
Up to Day 29
Title
Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Description
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.
Time Frame
Up to Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Must be modified Hoehn & Yahr Stage I-III inclusive. 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: 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). Participants with a history of psychosis or hallucinations within the previous 12 months. 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. 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). 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. Participants who have attempted suicide in the past. 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. 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christopher Goolsby
Phone
(689) 216-3107
Email
Christopher.Goolsby@ppd.com
Facility Information:
Facility Name
Los Alamitos, California
City
Los Alamitos
State/Province
California
ZIP/Postal Code
90720
Country
United States
Individual Site Status
Recruiting
Facility Name
Hollywood, Florida
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Individual Site Status
Recruiting
Facility Name
Orlando, Florida
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Name
South Miami, Florida
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Individual Site Status
Recruiting
Facility Name
Decatur, Georgia
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Individual Site Status
Recruiting
Facility Name
Farmington Hills, Michigan
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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