Open-label Trial in Parkinson's Disease (PD) (TEMPO-4)

58-Week Open-label Trial of Tavapadon in Parkinson's Disease (TEMPO-4 Trial)

The purpose of this study is to evaluate the safety and efficacy of long-term administration of flexible doses of tavapadon in participants with Parkinson's Disease.

Study Overview

• Status: Enrolling by invitation
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Tavapadon

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Erina, New South Wales, Australia, 2250
      • Erina, New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Kogarah
    • Sydney, New South Wales, Australia, 2050
      • Sydney, New South Wales
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Woolloongabba, Queensland
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Clayton, Victoria
    • Parkville, Victoria, Australia, 3050
      • Parkville, Victoria
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Medical center VITA1, Pleven
  • Pleven, Bulgaria, 5800
    • Pleven
  • Pleven, Bulgaria, 5800
    • Pleven, Bulgaria
  • Sofia, Bulgaria, 1142
    • Sofia
  • Sofia, Bulgaria, 1407
    • Sofia
  • Sofia, Bulgaria, 1431
    • Sofia
  • Sofia, Bulgaria, 1113
    • Multiprofile Hospital, Sofia
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y4E9
      • Ottawa, Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto, Ontario
• Czechia
  • Prague, Czechia, 100 00
    • Prague,
  • Prague, Czechia, 160 00
    • Prague,
  • Rychnov Nad Kněžnou, Czechia, 516 01
    • Rychnov nad Kněžnou
  • Chocen
    • Choceň, Chocen, Czechia, 56501
      • Chocen
  • Czech Republic
    • Prague, Czech Republic, Czechia, 150 00
      • Prague, Czech Republic
• France
  • Bron, France, 69500
    • Boulevard Pinel, Bron
  • Grenoble, France, 38043
    • Grenoble cedex
  • Nancy, France, 54035
    • Nancy
  • Nîmes cedex 09, France, 30029
    • Nîmes cedex 09
  • Strasbourg, France, 67098
    • Strasbourg
  • Toulouse, France, 31059
    • Toulouse Cedex 9
  • Creteil
    • Créteil, Creteil, France, 94010
      • Creteil,
• Germany
  • Bad Homburg, Germany, 61348
    • Bad Homburg
  • Berlin, Germany, 12163
    • Berlin
  • Bochum, Germany, 44791
    • Bochum
  • Gera, Germany, D-07551
    • Gera
  • Haag In Oberbayern, Germany, 83527
    • Haag in Oberbayern
  • Muenchen, Germany, 81377
    • Muenchen
  • Stadtroda, Germany, 07646
    • Stadtroda
  • Muenster
    • Münster, Muenster, Germany, 48149
      • Muenster
• Hungary
  • Budapest, Hungary, 1135
    • Budapest
  • Pécs, Hungary, 7623
    • Pecs
  • Tatabánya, Hungary, 2800
    • Tatabanya
• Israel
  • Haifa, Israel, 3109601
    • Haifa
  • Petah Tiqva, Israel, 49100
    • Petah Tiqva
  • Ramat Gan, Israel, 5265601
    • Ramat Gan
  • Tel Aviv, Israel, 6100000
    • Tel Aviv
• Italy
  • Cassino, Italy, 03043
    • Cassino
  • Milano, Italy, 20132
    • Milano
  • Milano, Italy, 20126
    • Milano, Italy
  • Padova, Italy, 35128
    • Padova
  • Pisa, Italy, 56126
    • Pisa
  • Rome, Italy, 00133
    • Rome
  • Rome, Italy, 00163
    • Rome
  • Rome, Italy, 00179
    • Rome
  • Torino, Italy, 10126
    • Torino
• Poland
  • Bydgoszcz, Poland, 85-163
    • Centrum Medyczne Neuromed
  • Katowice, Poland, 40-097
    • Katowice
  • Katowice, Poland, 40-123
    • Katowice
  • Krakow, Poland, 30-721
    • Kraków
  • Krakow, Poland, 30-539
    • Kraków
  • Kraków, Poland, 30-510
    • Kraków
  • Lublin, Poland, 20-701
    • Centrum Medyczne Hope Clinic Sebastian Szklener
  • Warsaw, Poland, 02-777
    • Singua
  • Cracow
    • Cracovia, Cracow, Poland, 31-505
      • Cracow
  • Siemianowice Slaskie
    • Siemianowice Śląskie, Siemianowice Slaskie, Poland, 41-100
      • Siemianowice Slaskie
• Serbia
  • Belgrade, Serbia, 11000
    • Belgrade
  • Belgrade, Serbia, 11060
    • Belgrade, Kragujevac
• Spain
  • Barcelona, Spain, 08035
    • Barcelona
  • Barcelona, Spain, 08041
    • Barcelona
  • Barcelona, Spain, 08190
    • Sant Cugat del Vallés Barcelona
  • Madrid, Spain, 28006
    • Madrid
  • Madrid, Spain, 28938
    • Móstoles, Madrid
  • San Sebastian, Spain, 20009
    • San Sebastian
  • Terrassa, Spain, 08222
    • Terrassa
  • Valencia, Spain, 46026
    • Valencia
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Elche
• Ukraine
  • Lviv, Ukraine
    • Lviv
  • Vinnitsa, Ukraine, 21050
    • Vinnitsa
  • Zaporizhzhya, Ukraine, 69035
    • Medical Center, Zaporizhzhya
  • Zaporiizhzhya
    • Zaporizhzhya, Zaporiizhzhya, Ukraine, 69600
      • Zaporiizhzhya
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Birmingham, Alabama
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock, Arkansas
  • California
    • Fountain Valley, California, United States, 92708
      • Fountain Valley, California
    • Fresno, California, United States, 93710
      • Fresno, California
    • Los Angeles, California, United States, 90048
      • Los Angeles, California
    • Pasadena, California, United States, 91105
      • Pasadena, California
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Englewood, Colorado
  • Florida
    • Adventura, Florida, United States, 33180
      • Florida, United States
    • Boca Raton, Florida, United States, 33486
      • Boca Raton, Florida
    • Coral Springs, Florida, United States, 33067
      • Coral Springs, Florida
    • Maitland, Florida, United States, 32751
      • Maitland, Florida
    • Ocala, Florida, United States, 34470
      • Ocala, Florida
    • Port Orange, Florida, United States, 32127
      • Port Orange, Florida
    • Tampa, Florida, United States, 33615
      • Tampa, Florida
    • Winter Park, Florida, United States, 32792
      • Winter Park, Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta, Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Chicago, Illinois
    • Winfield, Illinois, United States, 60190
      • Winfield, Illinois
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas City
  • Maine
    • Scarborough, Maine, United States, 04074
      • Scarborough, Maine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston, Massachusettes
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • East Lansing, Michigan
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Las Vegas, Nevada
  • New York
    • Albany, New York, United States, 12208
      • Albany, New York
    • Syracuse, New York, United States, 13210
      • Syracuse, New York
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Asheville, North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham, North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Cincinnati, Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland, Ohio
    • Columbus, Ohio, United States, 43221
      • Columbus, Ohio
    • Toledo, Ohio, United States, 43614
      • Toledo, Ohio
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia, Pennsylvania
  • Tennessee
    • Memphis, Tennessee, United States, 38157
      • Memphis, Tennessee
  • Texas
    • Georgetown, Texas, United States, 78628
      • Georgetown, Texas
    • Houston, Texas, United States, 77030
      • Houston, Texas
    • Lubbock, Texas, United States, 79410
      • Lubbock, Texas
    • Round Rock, Texas, United States, 78681
      • Round Rock, Texas
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Burlington, Vermont
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Richmond, Virginia
    • Richmond, Virginia, United States, 23233
      • Richmond, Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Virginia Beach, Virginia
  • Washington
    • Kirkland, Washington, United States, 98034
      • Kirkland, Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Rollover participants are eligible for the study if they met the following inclusion criteria:

• Participants who complete the 27-week double-blind Treatment Period of Trial CVL-751-PD-001 (NCT04201093) or Trial CVL-751 PD-003 (NCT04542499) or the 27-week double-blind Treatment Period and 10-day Safety/Withdrawal Assessment Period of Trial CVL-751-PD-002 (NCT04223193) and enter this trial within 72 hours after completing the last trial visit in the double-blind trial. Rollover participants from Trial CVL-751-PD-003 must continue to use levodopa/carbidopa (or levodopa/benserazide) for the duration of the trial.
• 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 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.
• Participant who, in the judgement of the investigator, demonstrated adequate compliance with the IMP and protocol requirements in the double-blind trial.

Key Exclusion criteria:

Rollover participants are excluded from the trial if any of the following met:

• Participants who do not enroll in this open-label trial within 72 hours after completing the last trial visit in the double-blind trial
• 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 who had previously been enrolled in this open-label trial and had subsequently withdrawn.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tavapadon; Participants will receive a Tavapadon tablet at a dose of 5 milligrams (mg) to 15 mg once daily (QD) orally during 58-week treatment period.	Drug: Tavapadon; Participants will receive Tavapadon at a dose of (5 to 15) mg QD, orally during a 58-week treatment period.; Other Names: PF-06649751; CVL-751

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Index	EQ-5D-5L is a survey instrument used for participant-reported outcome that measures health in 5 dimensions. The EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each has 5 levels of perceived problems (1 = no problem, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = extreme problems). Participant selects an answer for each of 5 dimensions considering the response that best matches his/her health "today". The digits for the 5 dimensions are combined into a 5-digit number that describes the participant's health state.	Baseline (Day 1), Weeks 32 and 58
Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scores (VAS)	EQ-5D-5L VAS is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. The EQ-5D-5L VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).	Baseline (Day 1), Weeks 32 and 58
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.	62 Weeks
Number of Participants Who Discontinued Study Treatment	A participant may discontinue the study treatment due to any of the following reasons: adverse event, death, worsening of PD symptoms to such an extent that, in the judgement of the investigator, the participant requires additional anti-PD medications, treatment with a prohibited concomitant medication, noncompliance with the trial schedule or procedures, withdrawal of consent, pregnancy, investigator discretion.	62 Weeks
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.	58 Weeks
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 participant may need to get more sleep, improve sleep practices, or seek medical attention to determine why he or she is sleepy.	58 Weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)	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).	60 Weeks
Study Medication Withdrawal Questionnaire (SMWQ)	SMWQ is a questionnaire to assess withdrawal symptoms subsequent to completion of dosing with Investigational medicinal product (IMP). The SMWQ is a modification of the Amphetamine Withdrawal Questionnaire, in which the first question "Have you been craving amphetamine or methamphetamine?" is replaced with "Have you been craving the trial medication?" This change is intended to prevent bias by implying that the trial medication might be an amphetamine or amphetamine-like stimulant when presented with the survey. Participants will complete the SMWQ onsite when they are at a designated trial visit; on days when the participant is not onsite, they will complete the SMWQ remotely.	60 Weeks
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III	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.	60 Weeks
Change From Baseline in the Hauser diary	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.	58 Weeks

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC
• Investigators: Study Director: Cari Combs, MD, Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Movement Disorders; Central Nervous System Diseases; Neurodegenerative Diseases; Brain Diseases; Parkinsonian Disorders
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: CVL-751-PD-004; 2019-002952-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No