Clinical trial NCT05610189: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: Parkinsonian Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine Agonist
Dopamine Therapy
Lead sponsor: Cerevel Therapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2022-11-09
Enrollment: 25
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCτ) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
Secondary outcomes:
measure: Minimum Steady-state Plasma Concentration (Cmin,ss) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Average Steady-state Plasma Concentration (Cavg,ss) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Trough Concentration (Ctrough) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Time of Maximum Observed Concentration (Tmax) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Degree of Fluctuation [(Cmax - Cmin)/Cavg,ss] of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Peak-to-Trough Ratio (PTR) of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Swing [(Cmax - Cmin)/Cmin,ss] of Tavapadon
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Apparent Clearance of Tavapadon From Plasma (CL/F)
timeFrame: Pre-dose and at multiple timepoints post-dose up to Day 28
measure: Number of Participants With Adverse Events (AEs) and AEs by Severity
timeFrame: Up to Day 36
measure: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values
timeFrame: Up to Day 29
measure: Number of Participants With Clinically Significant Changes in Vital Sign Values
timeFrame: Up to Day 29
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
timeFrame: Up to Day 29
measure: Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results
timeFrame: Up to Day 29
measure: Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Day 29
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: Los Alamitos, California
state: California
city: Hollywood
country: United States
facility: Hollywood, Florida
state: Florida
city: Orlando
country: United States
facility: Orlando, Florida
state: Florida
city: South Miami
country: United States
facility: South Miami, Florida
state: Florida
city: Decatur
country: United States
facility: Decatur, Georgia
state: Georgia
city: Farmington Hills
country: United States
facility: Farmington Hills, Michigan
state: Michigan
Study officials:
References: