Clinical trial NCT04223193: Flexible-Dose Trial in Early Parkinson's Disease (PD)
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 in Early Parkinson's Disease (TEMPO-2 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: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-01-10
Enrollment: 304
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 efficacy, safety, tolerability and pharmacokinetics (PK) of flexible doses of tavapadon in participants with Parkinson's Disease.


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 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.

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 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 )
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: 29 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: Fresno
country: United States
facility: Fresno, California
state: California
city: Boca Raton
country: United States
facility: Boca Raton, Florida
state: Florida
city: Maitland
country: United States
facility: Maitland, Florida
state: Florida
city: Ocala
country: United States
facility: Ocala, Florida
state: Florida
city: Winter Park
country: United States
facility: Winter Park, Florida
state: Florida
city: North Dartmouth
country: United States
facility: Boston Neuro Research Center
state: Massachusetts
city: Albany
country: United States
facility: Albany, New York
state: New York
city: Syracuse
country: United States
facility: Syracuse, New York
state: New York
city: Cincinnati
country: United States
facility: Cincinnati, Ohio
state: Ohio
city: Cleveland
country: United States
facility: Cleveland, Ohio
state: Ohio
city: Memphis
country: United States
facility: Memphis, Tennessee
state: Tennessee
city: Cypress
country: United States
facility: Cypress, 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: Richmond
country: United States
facility: Richmond, Virginia
state: Virginia
city: Richmond
country: United States
facility: Richmond, Virginia
state: Virginia
city: Kirkland
country: United States
facility: Kirkland, Washington
state: Washington
city: Sydney
country: Australia
facility: Macquarie Park, New South Wales
state: New South Wales
city: Marseille
country: France
facility: Marseille, France
city: Nantes
country: France
facility: Nantes CEDEX 1
city: Toulouse
country: France
facility: Toulouse Cedex 9
city: Berlin
country: Germany
facility: Berlin
city: Bochum
country: Germany
facility: Bochum
city: Gera
country: Germany
facility: Gera
city: Muenchen
country: Germany
facility: Muenchen
city: Budapest
country: Hungary
facility: Budapest
city: Pécs
country: Hungary
facility: Pecs
city: Tatabánya
country: Hungary
facility: Tatabanya
city: Cassino
country: Italy
facility: Cassino
city: Milano
country: Italy
facility: Milano
city: Rome
country: Italy
facility: Rome
city: Rozzano
country: Italy
facility: Rozzano Milano
city: Torino
country: Italy
facility: Torino
city: Seoul
country: Korea, Republic of
facility: Dongdaemun-gu, Seoul
state: Dongdaemun-gu
city: Busan
country: Korea, Republic of
facility: Haeundae-gu, Busan
state: Haeundae-gu
city: Seoul
country: Korea, Republic of
facility: Songpa-gu, Seoul
state: Songpa-gu
city: Cracovia
country: Poland
facility: Cracow
state: Cracow
city: Siemianowice Śląskie
country: Poland
facility: Siemianowice Slaskie
state: Siemianowice Slaskie
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne NEUROMED
city: Katowice
country: Poland
facility: Katowice
city: Lublin
country: Poland
facility: Centrum Medyczne Hope Clinic Sebastian Szklener
city: Belgrade
country: Serbia
facility: Belgrade
city: Barcelona
country: Spain
facility: Barcelona
city: Madrid
country: Spain
facility: Móstoles, Madrid
city: Zhongzheng
country: Taiwan
facility: Zhongzheng, Taipei
state: Taipei
city: Zhongzheng
country: Taiwan
facility: Zhongzheng, Taipei
state: Taipei
city: Ratchathewi
country: Thailand
facility: Ratchathewi, Bangkok
state: Bangkok
city: Khlong Luang
country: Thailand
facility: Khlong Luang, Pathum Thani
state: Pathum Thani
city: Nai Muang
country: Thailand
facility: Nai Muang, Ubon Ratchathani
state: Ubon Ratchathani
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: