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Flexible-Dose, Adjunctive Therapy Trial in Adults With Parkinson's Disease With Motor Fluctuations (TEMPO-3)

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ClinicalTrials.gov Identifier: NCT04542499
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : March 17, 2021
Sponsor:
Information provided by (Responsible Party):
Cerevel Therapeutics, LLC

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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Tavapadon Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 368 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 27, 2020
Estimated Primary Completion Date : June 11, 2022
Estimated Study Completion Date : August 11, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tavapadon
Participants will receive a tavapadon tablet titrated 5 to 15 milligrams (mg) once daily (QD) orally for 27 weeks.
Drug: Tavapadon
Participants will be randomized to receive tavapadon 5 to 15 mg tablet QD orally for 27 weeks.
Other Names:
  • PF-06649751
  • CVL-751

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




Primary Outcome Measures :
  1. 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) [ Time Frame: Up to 27 weeks ]
    The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total "on" time without troublesome dyskinesia will be assessed and reported at endpoint.


Secondary Outcome Measures :
  1. 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) [ Time Frame: Up to 27 weeks ]
    The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total daily "Off" time will be assessed and reported at endpoint.

  2. 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) [ Time Frame: Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27 ]
    The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total "on" time without troublesome dyskinesia will be assessed and reported at different time points.

  3. 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) [ Time Frame: Baseline, Weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27 ]
    The Hauser diary (Hauser et al, 2000) assesses participant-defined clinical status over a period of time and provides a tool for assessment of the change in "off" time and "on" time with troublesome dyskinesia (which is a more accurate reflection of clinical response than "off" time alone). The Hauser diary asks participants to rate their mobility for each 30-minute period and to record their status for the majority of the period in 1 of 5 categories as: "on" time without dyskinesia, "on" time with nontroublesome dyskinesia, "on" time with troublesome dyskinesia, "off" time, or asleep. The total daily "Off" time will be assessed and reported at different time points.

  4. Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score [ Time Frame: Up to 27 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 informed consent form (ICF) and in this protocol
  • Participants who are able, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures
  • 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 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 (MAO-B) inhibitors, amantadine, or anticholinergic drugs is permitted if use was initiated greater than (>) 90 days before signing of the informed consent, the dosage has remained stable for a minimum of 4 weeks before signing of the informed consent, and the dosage will remain stable for the duration of the trial (ie, no change in the COMT, MAO-B inhibitor, or amantadine dose is permitted during the trial).

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 who have had previous surgical intervention (eg, deep brain stimulation) for PD or for whom such a procedure is planned or anticipated during the trial period
  • Participants with an acute or chronic, clinically significant medical or psychiatric condition, cognitive impairment, or laboratory abnormality that might increase the risk associated with trial participation or administration of trial treatment or interfere with the interpretation of the trial results or that, in the judgment of the investigator, would make the Participant inappropriate for entry into this trial.- Medical conditions that are minor or well controlled may be considered acceptable if the condition does not expose the Participant to an undue risk of a significant AE or interfere with the assessments of safety or efficacy during the course of the trial. Participants with symptoms of anxiety or depression that are not debilitating and that are stable or adequately controlled with non-prohibited medication are considered acceptable. The medical monitor should be contacted in any instance where the investigator is uncertain regarding the stability of a Participant's medical conditions(s) and the potential impact of the condition(s) on trial participation
  • Participants with a history or current diagnosis of a clinically significant impulse control disorder (Disruptive, Impulse Control, and Conduct Disorder per DSM-5) (American Psychiatric Association, 2013)
  • 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 malignancy other than:
  • Non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in situ that was surgically removed in total >1 year before signing the ICF and had not recurred
  • Another type of malignancy that had been in remission for ≥5 years before signing the ICF and had not recurred
  • 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
  • Female Participants who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP
  • Participants who are currently receiving moderate or strong cytochrome P450 (CYP) 3A4 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 who are using any prohibited medication prior to randomization or who would be likely to require the use of prohibited concomitant medications during the trial
  • Participants with a Montreal Cognitive Assessment (MoCA) score <26
  • Participants with supine blood pressure greater than or equal to (>=)160 millimeters of Hg (mmHg) (systolic) or >=100 mmHg (diastolic) at the screening. The average of two supine measurements will be used to assess eligibility.
  • Participants with clinically significant orthostatic hypotension (eg, syncope)
  • Participants with a 12-lead ECG demonstrating a QTcF interval >450 msec. At screening: If the QTcF interval is >450 msec on the machine reading, the ECG should be repeated with 2 additional recordings. Based on the QTcF intervals that are reported by the central service, a participant will be excluded if the QTcF interval is >450 msec on 2 or more of the 3 ECG recordings, unless due to ventricular pacing. At baseline: If the QTcF interval is >450 msec on the machine readings, consult the medical monitor to determine whether the participant remains eligible to be randomized while awaiting the readings from the central service.
  • Participants with moderate or severe renal impairment (creatinine clearance as estimated by Cockcroft-Gault formula <30 milliliters per minute [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:
  • AST or 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. The medical monitor should be contacted to discuss individual cases, as needed. Tests with exclusionary results should be repeated to ensure reproducibility of the abnormality before excluding a Participant based on the criteria provided in the protocol. For medically significant or exclusory abnormal ECGs results, 2 additional ECG recordings should be collected, to ensure reproducibility of the abnormality, and the 3 ECG recordings read by the central service to confirm the abnormality before excluding a participant
  • Participants who previously participated in any tavapadon trial, including this trial, and received investigational medicinal product (IMP)
  • Participants who received treatment with any other investigational drug within 60 days before signing the ICF
  • Any Participant who, in the opinion of the sponsor, investigator, or medical monitor, should not participate in the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04542499


Locations
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Sponsors and Collaborators
Cerevel Therapeutics, LLC
Investigators
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Study Director: Matthew Leoni, MD Cerevel Therapeutics, LLC
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Responsible Party: Cerevel Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT04542499    
Other Study ID Numbers: CVL-751-PD-003
2019-002951-40 ( EudraCT Number )
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cerevel Therapeutics, LLC:
Parkinsonian Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Basal Ganglia Diseases
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases