Clinical trial NCT04201093: Fixed-Dose Trial in Early Parkinson's Disease (PD)
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses of Tavapadon in Early Parkinson's Disease (TEMPO-1 TRIAL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Keywords: Parkinsonian Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Lead sponsor: Cerevel Therapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2019-12-17
Enrollment: 522
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score
timeFrame: 27 Weeks
Secondary outcomes:
measure: Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II Score
timeFrame: 27 Weeks
measure: Percentage of Responders with "Much Improved" or "Very Much Improved" on Participant Global Impression of Change (PGIC ) at endpoint
timeFrame: 27 Weeks
measure: Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Combined Score
timeFrame: 27 Weeks
measure: Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score
timeFrame: 27 Weeks
measure: Change from Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score
timeFrame: 27 Weeks
measure: Clinical Global Impression - Improvement (CGI-I) Score
timeFrame: 27 Weeks
measure: Patient Global Impression of Change (PGIC) Score
timeFrame: 27 Weeks
measure: Epworth Sleepiness Scale (ESS)
timeFrame: 27 Weeks
measure: Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
timeFrame: 27 Weeks
measure: Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: 27 Weeks
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: 31 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham, Alabama
state: Alabama
city: Little Rock
country: United States
facility: Little Rock, Arkansas
state: Arkansas
city: Fountain Valley
country: United States
facility: Fountain Valley, California
state: California
city: Los Angeles
country: United States
facility: Los Angeles, California
state: California
city: Pasadena
country: United States
facility: Pasadena, California
state: California
city: Englewood
country: United States
facility: Englewood, Colorado
state: Colorado
city: Adventura
country: United States
facility: Adventura, Florida
state: Florida
city: Boca Raton
country: United States
facility: Boca Raton, Florida
state: Florida
city: Tampa
country: United States
facility: Tampa, Florida
state: Florida
city: Augusta
country: United States
facility: Augusta, Georgia
state: Georgia
city: Savannah
country: United States
facility: Savannah, Georgia
state: Georgia
city: Chicago
country: United States
facility: Chicago, Illinois
state: Illinois
city: Kansas City
country: United States
facility: Kansas City, Kansas
state: Kansas
city: Scarborough
country: United States
facility: Scarborough, Maine
state: Maine
city: Boston
country: United States
facility: Boston, Massachusetts
state: Massachusetts
city: East Lansing
country: United States
facility: East Lansing, Michigan
state: Michigan
city: Las Vegas
country: United States
facility: Las Vegas, Nevada
state: Nevada
city: Asheville
country: United States
facility: Asheville, North Carolina
state: North Carolina
city: Durham
country: United States
facility: Durham, North Carolina
state: North Carolina
city: Columbus
country: United States
facility: Columbus, Ohio
state: Ohio
city: Toledo
country: United States
facility: Toledo, Ohio
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia, Pennsylvania
state: Pennsylvania
city: Georgetown
country: United States
facility: Georgetown, Texas
state: Texas
city: Houston
country: United States
facility: Houston, Texas
state: Texas
city: Lubbock
country: United States
facility: Lubbock, Texas
state: Texas
city: Burlington
country: United States
facility: Burlington, Vermont
state: Vermont
city: Virginia Beach
country: United States
facility: Virginia Beach, Virginia
state: Virginia
city: Erina
country: Australia
facility: Erina, New South Wales
state: New South Wales
city: Woolloongabba
country: Australia
facility: Woolloongabba, Queensland
state: Queensland
city: Parkville
country: Australia
facility: Parkville, Victoria
state: Victoria
city: Pleven
country: Bulgaria
facility: Medical center VITA1, Pleven
city: Pleven
country: Bulgaria
facility: Pleven, Bulgaria
city: Pleven
country: Bulgaria
facility: Pleven
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital, Sofia
city: Sofia
country: Bulgaria
facility: Sofia
city: Sofia
country: Bulgaria
facility: Sofia
city: Sofia
country: Bulgaria
facility: DCC Neoclinic
city: Sofia
country: Bulgaria
facility: Sofia
city: Ottawa
country: Canada
facility: Ottawa, Ontario
state: Ontario
city: Toronto
country: Canada
facility: Toronto, Ontario
state: Ontario
city: Choceň
country: Czechia
facility: Poliklinika, Chocen,
state: Chocen
city: Prague
country: Czechia
facility: Prague,
city: Rychnov Nad Kněžnou
country: Czechia
facility: Rychnov nad Kněžnou
city: Créteil
country: France
facility: Creteil
state: Creteil
city: Bron
country: France
facility: Boulevard Pinel, Bron
city: Grenoble
country: France
facility: Grenoble cedex
city: Nancy
country: France
facility: Nancy, France
city: Nîmes
country: France
facility: Nîmes cedex
city: Münster
country: Germany
facility: Muenster
state: Muenster
city: Bad Homburg
country: Germany
facility: Bad Homburg
city: Duesseldorf
country: Germany
facility: Duesseldorf,
city: Haag In Oberbayern
country: Germany
facility: Haag in Oberbayern
city: Stadtroda
country: Germany
facility: Stadtroda
city: Haifa
country: Israel
facility: Haifa
city: Petah tikva
country: Israel
facility: Petah Tiqva
city: Ramat Gan
country: Israel
facility: Ramat Gan
city: Tel Aviv
country: Israel
facility: Tel Aviv
city: Milano
country: Italy
facility: Milano
city: Padova
country: Italy
facility: Padova
city: Pisa
country: Italy
facility: Pisa
city: Rome
country: Italy
facility: Rome
city: Rome
country: Italy
facility: Rome
city: Łódź
country: Poland
facility: Lodz
state: Lodz
city: Kraków
country: Poland
facility: Kraków
city: Warsaw
country: Poland
facility: Singua
city: Elche
country: Spain
facility: Elche
state: Alicante
city: Barcelona
country: Spain
facility: Barcelona
city: Barcelona
country: Spain
facility: Barcelona
city: Madrid
country: Spain
facility: Madrid
city: Madrid
country: Spain
facility: Madrid, Spain
city: Madrid
country: Spain
facility: Madrid, Spain
city: Terrassa
country: Spain
facility: Terrassa
city: Valencia
country: Spain
facility: Valencia
city: Zaporizhzhya
country: Ukraine
facility: Zaporiizhzhya
state: Zaporiizhzhya
city: Zaporozhye
country: Ukraine
facility: Zaporozhya
state: Zaporozhya
city: Dnipro
country: Ukraine
facility: Dnipro
city: Kharkiv
country: Ukraine
facility: Kharkiv
Study officials:
affiliation: Cerevel Therapeutics, LLC
name: Cari Combs, MD
role: STUDY_DIRECTOR
References: