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

NCT ID: NCT04201093

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 529 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-13
• Study Completion Date: 2024-06-28

Brief Summary

The purpose of this study is to evaluate the clinical efficacy, safety and pharmacokinetics (PK) of 2 fixed doses of tavapadon and placebo in participants with early PD.

Conditions

Parkinson Disease

Study Design

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

Study Groups

Tavapadon 5 mg

Participants will receive tavapadon tablet titrated up to 5 milligram (mg) once daily (QD) orally for 27 weeks.

Group Type: EXPERIMENTAL

Tavapadon

Intervention Type: DRUG

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

Tavapadon 15 mg

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

Group Type: EXPERIMENTAL

Tavapadon

Intervention Type: DRUG

Participants will be randomized to receive tavapadon 15mg 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 5mg 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

Tavapadon

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

Intervention Type: DRUG

Other Intervention Names

PF-06649751; CVL-751; 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 naïve or have a history of prior incidental treatment with dopaminergic agents (including Levodopa [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 monoamine oxidase B (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 (i.e, 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 Columbia-Suicide Severity Rating Scale (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., MD

Role: STUDY_DIRECTOR

AbbVie

Locations

Birmingham, Alabama

Birmingham, Alabama, United States

Little Rock, Arkansas

Little Rock, Arkansas, United States

Fountain Valley, California

Fountain Valley, California, United States

Los Angeles, California

Los Angeles, California, United States

Pasadena, California

Pasadena, California, United States

Englewood, Colorado

Englewood, Colorado, United States

Adventura, Florida

Adventura, Florida, United States

Boca Raton, Florida

Boca Raton, Florida, United States

Tampa, Florida

Tampa, Florida, United States

Augusta, Georgia

Augusta, Georgia, United States

Savannah, Georgia

Savannah, Georgia, United States

Chicago, Illinois

Chicago, Illinois, United States

Kansas City, Kansas

Kansas City, Kansas, United States

Scarborough, Maine

Scarborough, Maine, United States

Boston, Massachusetts

Boston, Massachusetts, United States

East Lansing, Michigan

East Lansing, Michigan, United States

Las Vegas, Nevada

Las Vegas, Nevada, United States

Asheville, North Carolina

Asheville, North Carolina, United States

Durham, North Carolina

Durham, North Carolina, United States

Columbus, Ohio

Columbus, Ohio, United States

Toledo, Ohio

Toledo, Ohio, United States

Philadelphia, Pennsylvania

Philadelphia, Pennsylvania, United States

Georgetown, Texas

Georgetown, Texas, United States

Houston, Texas

Houston, Texas, United States

Lubbock, Texas

Lubbock, Texas, United States

Burlington, Vermont

Burlington, Vermont, United States

Virginia Beach, Virginia

Virginia Beach, Virginia, United States

Erina, New South Wales

Erina, New South Wales, Australia

Woolloongabba, Queensland

Woolloongabba, Queensland, Australia

Parkville, Victoria

Parkville, Victoria, Australia

Medical center VITA1, Pleven

Pleven, , Bulgaria

Pleven, Bulgaria

Pleven, , Bulgaria

Pleven

Pleven, , Bulgaria

Multiprofile Hospital, Sofia

Sofia, , Bulgaria

Sofia

Sofia, , Bulgaria

Sofia

Sofia, , Bulgaria

DCC Neoclinic

Sofia, , Bulgaria

Sofia

Sofia, , Bulgaria

Ottawa, Ontario

Ottawa, Ontario, Canada

Toronto, Ontario

Toronto, Ontario, Canada

Poliklinika, Chocen,

Choceň, Chocen, Czechia

Prague,

Prague, , Czechia

Rychnov nad Kněžnou

Rychnov nad Kněžnou, , Czechia

Creteil

Créteil, Creteil, France

Boulevard Pinel, Bron

Bron, , France

Grenoble cedex

Grenoble, , France

Nancy, France

Nancy, , France

Nîmes cedex

Nîmes, , France

Muenster

Münster, Muenster, Germany

Bad Homburg

Bad Homburg, , Germany

Duesseldorf,

Düsseldorf, , Germany

Haag in Oberbayern

Haag in Oberbayern, , Germany

Stadtroda

Stadtroda, , Germany

Haifa

Haifa, , Israel

Petah Tiqva

Petah Tikva, , Israel

Ramat Gan

Ramat Gan, , Israel

Tel Aviv

Tel Aviv, , Israel

Milano

Milan, , Italy

Padova

Padua, , Italy

Pisa

Pisa, , Italy

Rome

Rome, , Italy

Rome

Rome, , Italy

Kraków

Krakow, , Poland

Singua

Warsaw, , Poland

Lodz

Lodz, Łódź Voivodeship, Poland

Elche

Elche, Alicante, Spain

Barcelona

Barcelona, , Spain

Barcelona

Barcelona, , Spain

Madrid

Madrid, , Spain

Madrid, Spain

Madrid, , Spain

Madrid, Spain

Madrid, , Spain

Terrassa

Terrassa, , Spain

Valencia

Valencia, , Spain

Zaporiizhzhya

Zaporizhzhya, Zaporiizhzhya, Ukraine

Zaporozhya

Zaporizhzhya, Zaporozhya, Ukraine

Dnipro

Dnipro, , Ukraine

Kharkiv

Kharkiv, , Ukraine

Countries

United States; Australia; Bulgaria; Canada; Czechia; France; Germany; Israel; Italy; Poland; Spain; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002949-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVL-751-PD-001

Identifier Type: -

Identifier Source: org_study_id