Clinical trial NCT04542499: Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations (TEMPO-3)
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon as Adjunctive Therapy for Parkinson's Disease in Levodopa-Treated Adults With Motor Fluctuations (TEMPO-3 Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Keywords: Parkinsonian Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Disease
Movement Disorders
Neurodegenerative Diseases
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-09-09
Enrollment: 507
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 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.


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 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-methyltransferase (COMT) inhibitors, monoamine oxidaseB (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 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 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 last6 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 5C-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 6months (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 12months. 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 aQTcF 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 Total "On" Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary)
timeFrame: Week 26
Secondary outcomes:
measure: 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)
timeFrame: Week 26
measure: 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)
timeFrame: Week 2, 5, 8, 11, 14, 18, 22, and 26
measure: 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)
timeFrame: Week 2, 5, 8, 11, 14, 18, 22, and 26
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: Week 26
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pheonix, Arizona
state: Arizona
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: Fresno
country: United States
facility: Fresno, California
state: California
city: Long Beach
country: United States
facility: Long beach, 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: Reseda
country: United States
facility: Reseda, California
state: California
city: Denver
country: United States
facility: Denver, Colorado
state: Colorado
city: Englewood
country: United States
facility: Englewood, Colorado
state: Colorado
city: Adventura
country: United States
facility: Adventura, Florida
state: Florida
city: Atlantis
country: United States
facility: Atlantis, Florida
state: Florida
city: Boca Raton
country: United States
facility: Boca Raton, Florida
state: Florida
city: Boca Raton
country: United States
facility: Boca Raton, Florida
state: Florida
city: Coral Springs
country: United States
facility: Coral Springs, Florida
state: Florida
city: Hallandale Beach
country: United States
facility: Hallandale Beach, Florida
state: Florida
city: Maitland
country: United States
facility: Maitland, Florida
state: Florida
city: Ocala
country: United States
facility: Ocala, Florida
state: Florida
city: Port Charlotte
country: United States
facility: Port Charlotte, Florida
state: Florida
city: Port Orange
country: United States
facility: Port Orange, Florida
state: Florida
city: Tampa
country: United States
facility: Tampa, Florida
state: Florida
city: Winter Park
country: United States
facility: Winter Park, Florida
state: Florida
city: Augusta
country: United States
facility: Augusta, Georgia
state: Georgia
city: Chicago
country: United States
facility: Chicago, Illinois
state: Illinois
city: Elk Grove Village
country: United States
facility: Elk Grove Village, Illinois
state: Illinois
city: Kansas City
country: United States
facility: Kansas City, Kansas
state: Kansas
city: Lexington
country: United States
facility: Lexington, Kentucky
state: Kentucky
city: Scarborough
country: United States
facility: Scarborough, Maine
state: Maine
city: Boston
country: United States
facility: Boston, Massachusettes
state: Massachusetts
city: North Dartmouth
country: United States
facility: Boston Neuro Research Center
state: Massachusetts
city: Farmington Hills
country: United States
facility: Farmington Hills, Michigan
state: Michigan
city: West Bloomfield
country: United States
facility: West Bloomfield, Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis, Missouri
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas, Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas, Nevada
state: Nevada
city: Syracuse
country: United States
facility: Syracuse, New York
state: New York
city: Asheville
country: United States
facility: Asheville, North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati, Ohio
state: Ohio
city: Cleveland
country: United States
facility: Cleveland, Ohio
state: Ohio
city: Columbus
country: United States
facility: Columbus, Ohio
state: Ohio
city: Dayton
country: United States
facility: Dayton, Ohio
state: Ohio
city: Toledo
country: United States
facility: Toledo, Ohio
state: Ohio
city: Memphis
country: United States
facility: Memphis, Tennessee
state: Tennessee
city: Cypress
country: United States
facility: Cypress, Texas
state: Texas
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: Round Rock
country: United States
facility: Round Rock, Texas
state: Texas
city: Burlington
country: United States
facility: Burlington, Vermont
state: Vermont
city: Richmond
country: United States
facility: Richmond, Virginia
state: Virginia
city: Richmond
country: United States
facility: Richmond, Virginia
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Beach, Virginia
state: Virginia
city: Kirkland
country: United States
facility: Kirkland, Washington
state: Washington
city: Spokane
country: United States
facility: Spokane, Washington
state: Washington
city: Clayton
country: Australia
facility: Clayton VIC
state: Clayton VIC
city: Erina
country: Australia
facility: Erina, New South Wales
state: New South Wales
city: Kogarah
country: Australia
facility: Kogarah, 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: 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: Chocen
state: Chocen
city: Prague
country: Czechia
facility: Prague, Czech Republic
state: Czech Republic
city: Prague
country: Czechia
facility: Prague,
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: Nantes
country: France
facility: Nantes CEDEX 1
city: Nîmes
country: France
facility: Nîmes cedex
city: Strasbourg
country: France
facility: Strasbourg
city: Toulouse
country: France
facility: Toulouse Cedex 9
city: Münster
country: Germany
facility: Muenster
state: Muenster
city: Bad Homburg
country: Germany
facility: Bad Homburg
city: Berlin
country: Germany
facility: Berlin
city: Bochum
country: Germany
facility: Bochum
city: Brandenburg
country: Germany
facility: Brandenburg, Germany
city: Duesseldorf
country: Germany
facility: Duesseldorf,
city: Gera
country: Germany
facility: Gera
city: Haag In Oberbayern
country: Germany
facility: Haag in Oberbayern
city: Muenchen
country: Germany
facility: Muenchen
city: Munich
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Stadtroda
country: Germany
facility: Stadtroda
city: Győr
country: Hungary
facility: Gyor,
state: Gyor
city: Budapest
country: Hungary
facility: Budapest
city: Pécs
country: Hungary
facility: Pecs
city: Szeged
country: Hungary
facility: Szeged
city: Ashkelon
country: Israel
facility: Ashkelon
city: Haifa
country: Israel
facility: Haifa
city: Jerusalem
country: Israel
facility: Jerusalem
city: Petah Tiqva
country: Israel
facility: Petah Tiqva
city: Shoham
country: Israel
facility: Shoham
city: Tel Aviv
country: Israel
facility: Tel Aviv
city: Ancona
country: Italy
facility: Ancona
city: Cassino
country: Italy
facility: Cassino
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: Rome
country: Italy
facility: Rome
city: Rozzano
country: Italy
facility: Rozzano Milano
city: Torino
country: Italy
facility: Torino
city: Cracovia
country: Poland
facility: Cracow
state: Cracow
city: Kraków
country: Poland
facility: Krakow
state: Krakow
city: Bydgoszcz
country: Poland
facility: Bydgoszcz, Kujawsko-Pomorskie
state: Kujawsko-Pomorskie
city: Łódź
country: Poland
facility: Lodz
state: Lodz
city: Siemianowice Śląskie
country: Poland
facility: Siemianowice Slaskie
state: Siemianowice Slaskie
city: Katowice
country: Poland
facility: Katowice
city: Katowice
country: Poland
facility: Katowice
city: Krakow
country: Poland
facility: Krakow
city: Kraków
country: Poland
facility: Kraków
city: Lublin
country: Poland
facility: Lublin
city: Lublin
country: Poland
facility: Centrum Medyczne Hope Clinic Sebastian Szklener
city: Warsaw
country: Poland
facility: Warsaw
city: Warsaw
country: Poland
facility: Singua
city: Belgrade
country: Serbia
facility: Belgrade, Serbia
city: Belgrade
country: Serbia
facility: Belgrade,
city: Belgrade
country: Serbia
facility: Belgrade
city: Belgrade
country: Serbia
facility: Belgrade, Kragujevac
city: Elche
country: Spain
facility: Elche
state: Alicante
city: Barcelona
country: Spain
facility: Barcelona
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: Pamplona
country: Spain
facility: Pamplona
city: San Sebastian
country: Spain
facility: San Sebastian
city: Sevilla
country: Spain
facility: Sevilla
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: Zaporozhye
country: Ukraine
facility: Zaporozhya
state: Zaporozhya
city: Dnipro
country: Ukraine
facility: Dnipro
city: Kharkiv
country: Ukraine
facility: Kharkiv
city: Kiev
country: Ukraine
facility: Kiev
city: Lviv
country: Ukraine
facility: Lviv
city: Vinnitsa
country: Ukraine
facility: Vinnitsa
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: