Flexible-Dose Trial in Early Parkinson's Disease (PD)

NCT ID: NCT04223193

Last Updated: 2025-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-06
• Study Completion Date: 2024-10-01

Brief Summary

The purpose of this study is to assess the efficacy, safety, tolerability and pharmacokinetics (PK) of flexible doses of tavapadon in participants with Parkinson's Disease.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tavapadon

Participants will receive tavapadon tablet titrated up to 15 milligram (mg) once daily (QD) orally for 27 weeks.

Group Type: EXPERIMENTAL

Tavapadon

Intervention Type: DRUG

Participants will be randomized to receive tavapadon 5 mg QD to 15 mg QD tablet once daily orally for 27 weeks.

Placebo

Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive placebo matching to tavapadon QD orally for 27 weeks.

Interventions

Tavapadon

Participants will be randomized to receive tavapadon 5 mg QD to 15 mg QD tablet once daily orally for 27 weeks.

Intervention Type: DRUG

Placebo

Participants will receive placebo matching to tavapadon QD orally for 27 weeks.

Intervention Type: DRUG

Other Intervention Names

PF-06649751; CVL-751

Eligibility Criteria

Inclusion Criteria

• Male and female participants aged 40 to 80 years, inclusive, at the time of signing the informed consent form (ICF).
• Sexually active men or women of childbearing potential must agree to use acceptable (at minimum) or highly effective birth control, or remain abstinent during the trial and for 4 weeks after the last dose of trial treatment.
• Participants who are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
• Participants with a diagnosis of PD that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria.
• Participants with modified Hoehn and Yahr stage 1, 1.5, or 2.
• Participants with disease duration (from time of diagnosis) of less than (<) 3 years and disease progression in the 3 years before signing the ICF.
• Participants with an MDS-UPDRS Part II score >=2 and Part III score >=10 at the Screening Visit and at the Baseline Visit.
• Participants with early PD who, in the opinion of the investigator, require pharmacologic intervention for disease management.
• Participants who are treatment naive or have a history of prior incidental treatment with dopaminergic agents (including L-Dopa and dopamine receptor agonist medications) for <3 months in total but not within 2 months of the Baseline Visit. Prior and concurrent use of MAO-B inhibitors is permitted if use was initiated >90 days before the Baseline Visit and the dosage will remain stable for the duration of the trial (ie, no change in the MAO-B inhibitor dose is permitted during the trial).
• Participants who are willing and able to refrain from any PD medications that are not permitted by the protocol (including dopaminergic agents) throughout participation in the trial.

Exclusion Criteria

• Participants with a history or clinical features consistent with essential tremor, atypical or secondary parkinsonian syndrome (including, but not limited to, progressive supra nuclear palsy, multiple system atrophy, cortico-basal degeneration, or drug-induced or post stroke parkinsonism).
• Participants with a history of nonresponse or insufficient response to L-Dopa at therapeutic dosages.
• Participants with a history or current diagnosis of a clinically significant impulse control disorder (Disruptive, Impulse Control, and Conduct Disorder per DSM-5).
• Participants with the presence of or history of brain tumor, hospitalization for severe head trauma, epilepsy (as defined by the International League Against Epilepsy), or seizures.
• Participants with a history of psychosis or hallucinations within the previous 12 months.
• Participants who answer "yes" on the C-SSRS Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or 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 the 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 with substance abuse or dependence disorder, including alcohol, benzodiazepines, and opioids, but excluding nicotine, within the past 6 months (180 days).
• Participants with dementia or cognitive impairment that, in the judgement of the investigator, would exclude the participant from understanding the ICF or participating in the trial.
• Participants with any condition that could possibly affect drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding).
• Participants who have a positive result for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibodies at screening.
• Participants with a history of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical intervention; second- or third-degree atrioventricular block; sick sinus syndrome; severe or unstable angina; or congestive heart failure within the last 12 months. A recent (less than or equal to [<=] 12 months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control.
• Participants with a history of neuroleptic malignant syndrome.
• Participants who are currently receiving moderate or strong CYP3A4 inducers or CYP3A4 inhibitors (except for topical administration).
• Participants with a positive urine drug screen for illicit drugs are excluded and may not be retested or rescreened. Participants with a positive urine drug screen resulting from use of marijuana (any Tetrahydrocannabinol [THC]-containing product), prescription, or over-the-counter medications or products that, in the investigator's documented opinion, do not signal a clinical condition that would impact the safety of the participant or interpretation of the trial results may continue evaluation for the trial following consultation and approval by the medical monitor.
• Participants with a Montreal Cognitive Assessment (MoCA) score <26.
• Participants with clinically significant orthostatic hypotension (eg, syncope).
• Participants with a 12-lead ECG demonstrating a QTcF interval >450 msec.
• Participants with moderate or severe renal impairment (creatinine clearance as estimated by Cockcroft-Gault formula <30 mL/min or on dialysis).
• Participants with any of the following abnormalities in clinical laboratory tests at the Screening Visit, as assessed by the central laboratory and confirmed by a single repeat measurement, if deemed necessary:

• Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) >=3 × Upper Limit Normal (ULN).
• Total bilirubin >=1.5 × ULN. Participants with a history of Gilbert's syndrome may be eligible provided they have a value <ULN for direct bilirubin.
• Participants with other abnormal laboratory test results, vital sign results, or ECG findings unless, in the judgment of the investigator, the findings are not medically significant and would not impact the safety of the participants or the interpretation of the trial results.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Fresno, California

Fresno, California, United States

Boca Raton, Florida

Boca Raton, Florida, United States

Maitland, Florida

Maitland, Florida, United States

Ocala, Florida

Ocala, Florida, United States

Winter Park, Florida

Winter Park, Florida, United States

Boston Neuro Research Center

North Dartmouth, Massachusetts, United States

Albany, New York

Albany, New York, United States

Syracuse, New York

Syracuse, New York, United States

Cincinnati, Ohio

Cincinnati, Ohio, United States

Cleveland, Ohio

Cleveland, Ohio, United States

Memphis, Tennessee

Memphis, Tennessee, United States

Cypress, Texas

Cypress, Texas, United States

Houston, Texas

Houston, Texas, United States

Lubbock, Texas

Lubbock, Texas, United States

Round Rock, Texas

Round Rock, Texas, United States

Richmond, Virginia

Richmond, Virginia, United States

Richmond, Virginia

Richmond, Virginia, United States

Kirkland, Washington

Kirkland, Washington, United States

Macquarie Park, New South Wales

Sydney, New South Wales, Australia

Marseille, France

Marseille, France, France

Nantes CEDEX 1

Nantes, Nantes, France

Toulouse Cedex 9

Toulouse, Toulouse, France

Bochum

Bochum, Bochum, Germany

Gera

Gera, Gera, Germany

Muenchen

München, Muenchen, Germany

Berlin

Berlin, State of Berlin, Germany

Budapest

Budapest, Budapest, Hungary

Pecs

Pécs, Hungary, Hungary

Tatabanya

Tatabánya, , Hungary

Cassino

Cassino, Cassino, Italy

Milano

Milan, Milano, Italy

Rome

Rome, Rome, Italy

Rozzano Milano

Rozzano, , Italy

Torino

Torino, , Italy

Cracow

Krakow, Cracow, Poland

Katowice

Katowice, Katowice, Poland

Siemianowice Slaskie

Siemianowice Śląskie, Siemianowice Slaskie, Poland

Centrum Medyczne NEUROMED

Bydgoszcz, , Poland

Centrum Medyczne Hope Clinic Sebastian Szklener

Lublin, , Poland

Belgrade

Belgrade, Belgrade, Serbia

Dongdaemun-gu, Seoul

Seoul, Dongdaemun-gu, South Korea

Haeundae-gu, Busan

Busan, Haeundae-gu, South Korea

Songpa-gu, Seoul

Seoul, Songpa-gu, South Korea

Barcelona

Barcelona, Barcelona, Spain

Móstoles, Madrid

Madrid, Madrid, Spain

Zhongzheng, Taipei

Zhongzheng, Taipei, Taiwan

Zhongzheng, Taipei

Zhongzheng, Taipei, Taiwan

Ratchathewi, Bangkok

Ratchathewi, Bangkok, Thailand

Khlong Luang, Pathum Thani

Khlong Luang, Changwat Pathum Thani, Thailand

Nai Muang, Ubon Ratchathani

Nai Muang, Changwat Ubon Ratchathani, Thailand

Kiev

Kiev, Kyiv City, Ukraine

Lviv

Lviv, Lviv Oblast, Ukraine

Vinnitsa

Vinnitsa, Vinnitsa, Ukraine

Countries

United States; Australia; France; Germany; Hungary; Italy; Poland; Serbia; South Korea; Spain; Taiwan; Thailand; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002950-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVL-751-PD-002

Identifier Type: -

Identifier Source: org_study_id