Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations

Phase 3

Completed

• Conditions: Parkinson Disease
• Interventions: Drug: Placebo; Drug: Tavapadon

• Registration Number: NCT04542499
• Lead Sponsor: Cerevel Therapeutics, LLC

Brief Summary

The purpose of this study is to assess the effect of tavapadon on the change from baseline in total daily hours of "on" time without troublesome dyskinesia in L-Dopa-treated participants with Parkinson's Disease (PD) who are experiencing motor fluctuations.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-02
• Study First Submitted QC: 2020-09-02
• Study First Posted: 2020-09-09
• Study Start: 2020-10-27
• Primary Completion: 2024-01-29
• Study Completion: 2024-02-15
• Disposition First Posted: 2024-04-15
• Status Verified: 2024-12
• Disposition First Submitted: 2024-12-13
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 507

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 this protocol.
• Participants with a diagnosis of PD that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria, with bradykinesia and motor asymmetry.
• Participants with modified Hoehn and Yahr stage 2, 2.5, or 3 in the "on" state.
• Participants with a good response to levodopa (L-Dopa) in the judgment of the investigator.
• Participants who return a completed self-reported home diary for motor function status (Hauser diary) during the screening period (after diary training and concordance testing has occurred), with recordings for 2 consecutive days (ie, 2 consecutive 24-hour periods) showing at least 2 and half hours of "off" time on each of the 2 days.
• Participants who are on a stable dose of L-Dopa for at least 4 weeks prior to screening and are taking a minimum total daily dose of 400 milligram (mg) divided in at least 4 doses per day of standard carbidopa/levodopa or divided in at least 3 doses per day of extended-release carbidopa/levodopa capsules. The carbidopa/levodopa dose and frequency must be maintained for the duration of the trial.
• Prior and concurrent use of catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine, istradefylline or anticholinergic drugs are permitted if the use was initiated greater than (>) 90 days before the baseline visit and the dosage will remain stable for the duration of the trial (ie, no change in the COMT, MAO-B inhibitor, amantadine, istradefylline or anticholinergic dose is permitted during the trial).

Key

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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 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-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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.
Tavapadon	Tavapadon	Participants will receive a tavapadon tablet titrated 5 to 15 milligrams (mg) once daily (QD) orally for 27 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Total "On" Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary)	27 Weeks	The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total "on" time without troublesome dyskinesia will be assessed and reported at endpoint.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Total Daily "Off" Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary)	27 Weeks	The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total daily "Off" time will be assessed and reported at endpoint.
Change From Baseline in the Total "On" Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary)	Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27	The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total "on" time without troublesome dyskinesia will be assessed and reported at different time points.
Change From Baseline in Total Daily "Off" Time Without Troublesome Dyskinesia Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary)	Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27	The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total daily "Off" time will be assessed and reported at different time points.
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score	27 Weeks	The MDS-UPDRS is a multidimensional scale that assesses the motor and non-motor impacts of PD across 4 parts. Part I, non-motor aspects of experiences of daily living, comprises 13 items, 6 of which are rated by the physician (Part IA) and 7 of which are rated by the participant (Part IB). Part II, motor aspects of experiences of daily living, comprises 13 items that are rated by the participant. Part III, motor examination, comprises 18 items that are assessed by the investigator (resulting in 33 scores by location and lateralization). Part IV, motor complications, comprises 6 item (3 items for dyskinesia and 3 items for fluctuation) and requires the physician to use historical and objective information to assess dyskinesia and motor fluctuations. Each item of all the parts will be rated on a scale from 0 to 4 on which 0 = normal, 1=slight, 2=mild, 3=moderate, and 4=severe. Change from baseline in MDS-UPDRS parts I, II and III Individual score will be assessed.

Trial Locations

Locations (75)

Chicago, Illinois; 🇺🇸 Chicago, Illinois, United States

Boston, Massachusettes; 🇺🇸 Boston, Massachusetts, United States

Cleveland, Ohio; 🇺🇸 Cleveland, Ohio, United States

Frenso, California; 🇺🇸 Fresno, California, United States

Coral Springs, Florida; 🇺🇸 Coral Springs, Florida, United States

Boca Raton, Florida; 🇺🇸 Boca Raton, Florida, United States

Los Angeles, California; 🇺🇸 Los Angeles, California, United States

Adventura, Florida; 🇺🇸 Florida City, Florida, United States

Hallandale Beach, Florida; 🇺🇸 Hallandale Beach, Florida, United States

Maitland, Florida; 🇺🇸 Maitland, Florida, United States

Ocala, Florida; 🇺🇸 Ocala, Florida, United States

Port Charlotte, Florida; 🇺🇸 Port Charlotte, Florida, United States

Port Orange, Florida; 🇺🇸 Port Orange, Florida, United States

Winter Park, Florida; 🇺🇸 Winter Park, Florida, United States

Tampa, Florida; 🇺🇸 Tampa, Florida, United States

Augusta, Georgia; 🇺🇸 Augusta, Georgia, United States

Toledo, Ohio; 🇺🇸 Toledo, Ohio, United States

Cypress, Texas; 🇺🇸 Cypress, Texas, United States

Columbus, Ohio; 🇺🇸 Columbus, Ohio, United States

Lubbock, Texas; 🇺🇸 Lubbock, Texas, United States

Round Rock, Texas; 🇺🇸 Round Rock, Texas, United States

Toulouse Cedex; 🇫🇷 Toulouse, France

Richmond, Virginia; 🇺🇸 Richmond, Virginia, United States

Kogarah, New South Wales; 🇦🇺 Kogarah, New South Wales, Australia

Kirkland, Washington; 🇺🇸 Kirkland, Washington, United States

Erina, New South Wales; 🇦🇺 Erina, New South Wales, Australia

Woolloongabba, Queensland; 🇦🇺 Woolloongabba, Queensland, Australia

Parkville, Victoria; 🇦🇺 Parkville, Victoria, Australia

Sofia; 🇧🇬 Sofia, Bulgaria

Pleven; 🇧🇬 Pleven, Bulgaria

Chocen; 🇨🇿 Choceň, Chocen, Czechia

Prague; 🇨🇿 Prague, Czechia

Prague,; 🇨🇿 Prague, Czechia

Rychnov nad Kněžnou; 🇨🇿 Rychnov Nad Kněžnou, Czechia

Nantes CEDEX 1; 🇫🇷 Nantes, France

Creteil,; 🇫🇷 Créteil, Creteil, France

Nîmes cedex; 🇫🇷 Nîmes, France

Muenster; 🇩🇪 Münster, Muenster, Germany

Bad Homburg; 🇩🇪 Bad Homburg, Germany

Bochum; 🇩🇪 Bochum, Germany

Gera; 🇩🇪 Gera, Germany

Brandenburg,; 🇩🇪 Brandenburg, Germany

Tel Aviv; 🇮🇱 Tel Aviv, Israel

Haag in Oberbayern; 🇩🇪 Haag In Oberbayern, Germany

Klinikum rechts der Isar der TU München; 🇩🇪 München, Germany

Muenchen; 🇩🇪 Muenchen, Germany

Milano; 🇮🇹 Milano, Italy

Rozzano Milano; 🇮🇹 Rozzano, Italy

Kraków; 🇵🇱 Kraków, Poland

Kragujevac; 🇷🇸 Kragujevac, Serbia

Warsaw,; 🇵🇱 Warsaw, Poland

Terrassa; 🇪🇸 Terrassa, Spain

Elche; 🇪🇸 Elche, Alicante, Spain

Madrid; 🇪🇸 Madrid, Spain

Lviv; 🇺🇦 Lviv, Ukraine

Vinnitsa; 🇺🇦 Vinnitsa, Ukraine

Barcelona; 🇪🇸 Barcelona, Spain

Lublin; 🇵🇱 Lublin, Poland

Berlin; 🇩🇪 Berlin, Germany

Ancona; 🇮🇹 Ancona, Italy

Las Vegas, Nevada; 🇺🇸 Las Vegas, Nevada, United States

Houston,Texas; 🇺🇸 Houston, Texas, United States

Farmington Hills, Michigan; 🇺🇸 Farmington Hills, Michigan, United States

Krakow; 🇵🇱 Krakow, Poland

Siemianowice Slaskie; 🇵🇱 Siemianowice Śląskie, Siemianowice Slaskie, Poland

Scarborough, Maine; 🇺🇸 Scarborough, Maine, United States

Bydgoszcz; 🇵🇱 Bydgoszcz, Poland

Katowice; 🇵🇱 Katowice, Poland

Little Rock, Arkansas; 🇺🇸 Little Rock, Arkansas, United States

North Dartmouth, Massachusetts; 🇺🇸 North Dartmouth, Massachusetts, United States

Memphis, Tennessee; 🇺🇸 Memphis, Tennessee, United States

Cassino; 🇮🇹 Cassino, Italy

Padova; 🇮🇹 Padova, Italy

Rome; 🇮🇹 Rome, Italy

Pisa; 🇮🇹 Pisa, Italy