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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05610189
• Other study ID #: CVL-751-1006
• Status: Completed
• Phase: Phase 1
• Start date: December 15, 2022
• Est. completion date: December 17, 2023

Study information

• Verified date: February 2024
• Source: Cerevel Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 17, 2023
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Tavapadon
Oral tablets

Locations

Country	Name	City	State
United States	Decatur, Georgia	Decatur	Georgia
United States	Farmington Hills, Michigan	Farmington Hills	Michigan
United States	Hollywood, Florida	Hollywood	Florida
United States	Los Alamitos, California	Los Alamitos	California
United States	Orlando, Florida	Orlando	Florida
United States	South Miami, Florida	South Miami	Florida

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