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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04542499




Registration number
NCT04542499
Ethics application status
Date submitted
2/09/2020
Date registered
9/09/2020

Titles & IDs
Public title
Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations
Scientific 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)
Secondary ID [1] 0 0
2019-002951-40
Secondary ID [2] 0 0
CVL-751-PD-003
Universal Trial Number (UTN)
Trial acronym
TEMPO-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tavapadon
Treatment: Drugs - Placebo

Experimental: Tavapadon - Participants will receive a tavapadon tablet titrated 5 to 15 milligrams (mg) once daily (QD) orally for 27 weeks.

Placebo comparator: Placebo - Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.


Treatment: Drugs: Tavapadon
Participants will be randomized to receive tavapadon 5 to 15 mg tablet QD orally for 27 weeks.

Treatment: Drugs: Placebo
Participants will receive placebo matching to tavapadon QD orally for 27 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
27 Weeks
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
27 Weeks
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27
Secondary outcome [4] 0 0
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score
Timepoint [4] 0 0
27 Weeks

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Erina, New South Wales - Erina
Recruitment hospital [2] 0 0
Kogarah, New South Wales - Kogarah
Recruitment hospital [3] 0 0
Woolloongabba, Queensland - Woolloongabba
Recruitment hospital [4] 0 0
Parkville, Victoria - Parkville
Recruitment postcode(s) [1] 0 0
2250 - Erina
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maine
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Nevada
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Pleven
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
Country [17] 0 0
Czechia
State/province [17] 0 0
Chocen
Country [18] 0 0
Czechia
State/province [18] 0 0
Prague
Country [19] 0 0
Czechia
State/province [19] 0 0
Rychnov Nad Knežnou
Country [20] 0 0
France
State/province [20] 0 0
Creteil
Country [21] 0 0
France
State/province [21] 0 0
Nantes
Country [22] 0 0
France
State/province [22] 0 0
Nîmes
Country [23] 0 0
France
State/province [23] 0 0
Toulouse
Country [24] 0 0
Germany
State/province [24] 0 0
Muenster
Country [25] 0 0
Germany
State/province [25] 0 0
Bad Homburg
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Bochum
Country [28] 0 0
Germany
State/province [28] 0 0
Brandenburg
Country [29] 0 0
Germany
State/province [29] 0 0
Gera
Country [30] 0 0
Germany
State/province [30] 0 0
Haag In Oberbayern
Country [31] 0 0
Germany
State/province [31] 0 0
Muenchen
Country [32] 0 0
Germany
State/province [32] 0 0
München
Country [33] 0 0
Israel
State/province [33] 0 0
Tel Aviv
Country [34] 0 0
Italy
State/province [34] 0 0
Ancona
Country [35] 0 0
Italy
State/province [35] 0 0
Cassino
Country [36] 0 0
Italy
State/province [36] 0 0
Milano
Country [37] 0 0
Italy
State/province [37] 0 0
Padova
Country [38] 0 0
Italy
State/province [38] 0 0
Pisa
Country [39] 0 0
Italy
State/province [39] 0 0
Rome
Country [40] 0 0
Italy
State/province [40] 0 0
Rozzano
Country [41] 0 0
Poland
State/province [41] 0 0
Siemianowice Slaskie
Country [42] 0 0
Poland
State/province [42] 0 0
Bydgoszcz
Country [43] 0 0
Poland
State/province [43] 0 0
Katowice
Country [44] 0 0
Poland
State/province [44] 0 0
Krakow
Country [45] 0 0
Poland
State/province [45] 0 0
Kraków
Country [46] 0 0
Poland
State/province [46] 0 0
Lublin
Country [47] 0 0
Poland
State/province [47] 0 0
Warsaw
Country [48] 0 0
Serbia
State/province [48] 0 0
Kragujevac
Country [49] 0 0
Spain
State/province [49] 0 0
Alicante
Country [50] 0 0
Spain
State/province [50] 0 0
Barcelona
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Terrassa
Country [53] 0 0
Ukraine
State/province [53] 0 0
Lviv
Country [54] 0 0
Ukraine
State/province [54] 0 0
Vinnitsa

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cerevel Therapeutics, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Cari Combs, MD
Address 0 0
Cerevel Therapeutics, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.