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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04201093




Registration number
NCT04201093
Ethics application status
Date submitted
13/12/2019
Date registered
17/12/2019
Date last updated
18/03/2021

Titles & IDs
Public title
Fixed-Dose Trial in Early Parkinson's Disease (PD)
Scientific 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)
Secondary ID [1] 0 0
2019-002949-38
Secondary ID [2] 0 0
CVL-751-PD-001
Universal Trial Number (UTN)
Trial acronym
TEMPO-1
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 5 mg - Participants will receive tavapadon tablet titrated up to 5 milligram (mg) once daily (QD) orally for 27 weeks.

Experimental: Tavapadon 15 mg - Participants will receive tavapadon tablet titrated up to 15 milligram (mg) 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 mg QD or 15 mg QD tablet once daily 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 Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score - The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) retains the four-scale structure with a reorganization of the various subscales. Part II contains 13 sub-scores for the motor experiences of daily living and Part III, 33 sub-scores based on 18 items, several with right, left or other body distribution scores for the motor examination. Each sub-score is anchored with 5 responses that are linked to the commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The sub-score for each is summed to calculate the total scores. The scale range for Part II+III Total Score is 0-184 (Part II maximum total score 52 + Part III maximum total score132). The higher the score the greater the severity. A negative change from baseline represents an improvement in motor function.
Timepoint [1] 0 0
Up to 27 weeks
Secondary outcome [1] 0 0
Percentage of Responders with "Much Improved" or "Very Much Improved" on Participant Global Impression of Change (PGIC ) at endpoint - The PGIC is the participant-reported outcome. The qualitative assessment of meaningful change will be determined by the participant in response to the question, "Compared to your condition at the beginning of treatment, how much has your condition changed?" Scores are: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. Percentage of responders with much improved and very much improved on PGIC scale will be assessed.
Timepoint [1] 0 0
Up to 27 Weeks
Secondary outcome [2] 0 0
Patient Global Impression of Change (PGIC) Score - The PGIC is the participant-reported outcome. The qualitative assessment of meaningful change will be determined by the participant in response to the question, "Compared to your condition at the beginning of treatment, how much has your condition changed?" Scores are: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse.
Timepoint [2] 0 0
Up to 27 Weeks
Secondary outcome [3] 0 0
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Combined Score - 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 combined score will be assessed.
Timepoint [3] 0 0
Up to 27 Weeks
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 - 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.
Timepoint [4] 0 0
Up to 27 Weeks
Secondary outcome [5] 0 0
Change from Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score - CGI-S scale is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of the assessment relative to the clinician's past experience with participants who have the same diagnosis. Raters select one response based on the following question: "Considering your total clinical experience with this particular population, how ill is the participant at this time?" Scores are: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Change from baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score will be assessed.
Timepoint [5] 0 0
Up to 27 Weeks
Secondary outcome [6] 0 0
Clinical Global Impression - Improvement (CGI-I) Score - CGI-I a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to the baseline state at the beginning of the intervention. Raters select one response based on the following question, "Compared to your patient's condition at the beginning of treatment, how much has your patient changed?" Scores are: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. Clinical Global Impression - Improvement (CGI-I) will be assessed.
Timepoint [6] 0 0
Up to 27 Weeks
Secondary outcome [7] 0 0
Epworth Sleepiness Scale (ESS) - ESS is a scale that is intended to measure daytime sleepiness. It assesses the likelihood of dozing off or falling asleep in the following common situations: sitting and reading, sitting inactive in a public place as a passenger in a car for an hour or more without stopping for a break, lying down to rest when circumstances permit, sitting and talking to someone, sitting quietly after a meal without alcohol, and in a car while stopped for a few minutes in traffic or at a light. Each situation is rated as 0=would never nod off, 1=slight chance of nodding off, 2=moderate chance of nodding off, or 3=high chance of nodding off. A score greater than or equal to (> =) 10 indicates that the patient may need to get more sleep, improve sleep practices, or seek medical attention to determine why he or she is sleepy.
Timepoint [7] 0 0
Up to 27 Weeks
Secondary outcome [8] 0 0
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) - QUIP-RS is a global screening instrument that assesses impulse control disorders (ICDs) and related disorders (punding, hobbyism, and dopamine dysregulation syndrome) in participants with PD. The QUIP-RS has 4 primary questions that pertain to commonly reported thoughts, urges/desires, and behaviors associated with ICDs, each of which is applied to 4 ICDs (compulsive gambling, buying, eating, sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). The QUIP-RS uses a 5-point Likert scale (score 0-4 [0 means "never" and 4 means "very often"] for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16, with a higher score indicating greater severity (frequency) of symptoms. The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112.
Timepoint [8] 0 0
Up to 27 Weeks
Secondary outcome [9] 0 0
Columbia-Suicide Severity Rating Scale (C-SSRS) - The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).
Timepoint [9] 0 0
Up to 27 Weeks
Secondary outcome [10] 0 0
Number of Participants with Treatment Emergent Adverse Events (TEAEs) - An AE is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, Vital Signs, Physical and Neurological evaluations and ECGs will be reported as TEAEs.
Timepoint [10] 0 0
Up to 31 Weeks

Eligibility
Key inclusion criteria
- Male and female participants aged 40 to 80 years, inclusive, at the time of signing
the ICF (Informed consent form)

- 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 with a diagnosis of 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 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 informed consent form (ICF)

- Participants with an MDS-UPDRS Part II score greater than or equal to (>=)2 and Part
III score >=10 at the screening 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 L-Dopa and dopamine receptor agonist medications)
for <3 months and not within 2 months of signing the ICF. Prior and concurrent use of
Monoamine oxidase (MAO)-B inhibitors is permitted if use was initiated > 90 days
before signing of the ICF 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
Minimum age
40 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion

- 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 or 2 or
more other antiparkinsonian drugs 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 based on medical records or participant/caregiver feedback

- 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 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.

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
Recruiting
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
Woolloongabba, Queensland - Woolloongabba
Recruitment hospital [3] 0 0
Parkville, Victoria - Parkville
Recruitment postcode(s) [1] 0 0
02250 - Erina
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maine
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
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
Vermont
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Czechia
State/province [16] 0 0
Chocen
Country [17] 0 0
Czechia
State/province [17] 0 0
Prague
Country [18] 0 0
Czechia
State/province [18] 0 0
Rychnov Nad KneĹžnou
Country [19] 0 0
France
State/province [19] 0 0
Creteil
Country [20] 0 0
France
State/province [20] 0 0
Bron
Country [21] 0 0
France
State/province [21] 0 0
Grenoble
Country [22] 0 0
France
State/province [22] 0 0
Nîmes
Country [23] 0 0
Germany
State/province [23] 0 0
Muenster
Country [24] 0 0
Germany
State/province [24] 0 0
Bad Homburg
Country [25] 0 0
Germany
State/province [25] 0 0
Haag In Oberbayern
Country [26] 0 0
Germany
State/province [26] 0 0
Westerstede
Country [27] 0 0
Israel
State/province [27] 0 0
Jerusalem
Country [28] 0 0
Israel
State/province [28] 0 0
Petah tikva
Country [29] 0 0
Italy
State/province [29] 0 0
Rome
Country [30] 0 0
Poland
State/province [30] 0 0
Lodz
Country [31] 0 0
Poland
State/province [31] 0 0
Katowice
Country [32] 0 0
Poland
State/province [32] 0 0
Lublin
Country [33] 0 0
Poland
State/province [33] 0 0
Warsaw
Country [34] 0 0
Spain
State/province [34] 0 0
Alicante
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Spain
State/province [37] 0 0
Sevilla
Country [38] 0 0
Spain
State/province [38] 0 0
Terrassa
Country [39] 0 0
Spain
State/province [39] 0 0
Valencia

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

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04201093
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Matthew Leoni, 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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04201093