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

Parkinson Disease Clinical Trial

— TEMPO-4  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04760769
• Other study ID #: CVL-751-PD-004
• Secondary ID: 2019-002952-17
• Status: Enrolling by invitation
• Phase: Phase 3
• Start date: February 24, 2021
• Est. completion date: January 2026

Study information

• Verified date: April 2024
• Source: Cerevel Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1200
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Tavapadon
Participants will receive Tavapadon at a dose of (5 to 15) mg QD, orally during a 58-week treatment period.

Locations

Country	Name	City	State
Australia	Clayton, Victoria	Clayton	Victoria
Australia	Erina, New South Wales	Erina	New South Wales
Australia	Kogarah	Kogarah	New South Wales
Australia	Parkville, Victoria	Parkville	Victoria
Australia	Sydney, New South Wales	Sydney	New South Wales
Australia	Woolloongabba, Queensland	Woolloongabba	Queensland
Bulgaria	Medical center VITA1, Pleven	Pleven
Bulgaria	Pleven	Pleven
Bulgaria	Pleven, Bulgaria	Pleven
Bulgaria	Multiprofile Hospital, Sofia	Sofia
Bulgaria	Sofia	Sofia
Bulgaria	Sofia	Sofia
Bulgaria	Sofia	Sofia
Canada	Ottawa, Ontario	Ottawa	Ontario
Canada	Toronto, Ontario	Toronto	Ontario
Czechia	Chocen	Chocen	Chocen
Czechia	Prague,	Prague
Czechia	Prague,	Prague
Czechia	Prague, Czech Republic	Prague	Czech Republic
Czechia	Rychnov nad Knežnou	Rychnov Nad Knežnou
France	Boulevard Pinel, Bron	Bron
France	Creteil,	Créteil	Creteil
France	Grenoble cedex	Grenoble
France	Nancy	Nancy
France	Nîmes cedex 09	Nîmes cedex 09
France	Strasbourg	Strasbourg
France	Toulouse Cedex 9	Toulouse
Germany	Bad Homburg	Bad Homburg
Germany	Berlin	Berlin
Germany	Bochum	Bochum
Germany	Gera	Gera
Germany	Haag in Oberbayern	Haag In Oberbayern
Germany	Muenchen	Muenchen
Germany	Muenster	Münster	Muenster
Germany	Stadtroda	Stadtroda
Hungary	Budapest	Budapest
Hungary	Pecs	Pécs
Hungary	Tatabanya	Tatabánya
Israel	Haifa	Haifa
Israel	Petah Tiqva	Petah Tiqva
Israel	Ramat Gan	Ramat Gan
Israel	Tel Aviv	Tel Aviv
Italy	Cassino	Cassino
Italy	Milano	Milano
Italy	Milano, Italy	Milano
Italy	Padova	Padova
Italy	Pisa	Pisa
Italy	Rome	Rome
Italy	Rome	Rome
Italy	Rome	Rome
Italy	Torino	Torino
Poland	Centrum Medyczne NEUROMED	Bydgoszcz
Poland	Cracow	Cracovia	Cracow
Poland	Katowice	Katowice
Poland	Katowice	Katowice
Poland	Krakow	Krakow
Poland	Krakow	Krakow
Poland	Kraków	Kraków
Poland	Centrum Medyczne Hope Clinic Sebastian Szklener	Lublin
Poland	Siemianowice Slaskie	Siemianowice Slaskie	Siemianowice Slaskie
Poland	Singua	Warsaw
Serbia	Belgrade	Belgrade
Serbia	Belgrade, Kragujevac	Belgrade
Spain	Barcelona	Barcelona
Spain	Barcelona	Barcelona
Spain	Sant Cugat del Vallés Barcelona	Barcelona
Spain	Elche	Elche	Alicante
Spain	Madrid	Madrid
Spain	Móstoles, Madrid	Madrid
Spain	San Sebastian	San Sebastian
Spain	Terrassa	Terrassa
Spain	Valencia	Valencia
Ukraine	Lviv	Lviv
Ukraine	Vinnitsa	Vinnitsa
Ukraine	Medical Center, Zaporizhzhya	Zaporizhzhya
Ukraine	Zaporiizhzhya	Zaporizhzhya	Zaporiizhzhya
United States	Florida, United States	Adventura	Florida
United States	Albany, New York	Albany	New York
United States	Asheville, North Carolina	Asheville	North Carolina
United States	Augusta, Georgia	Augusta	Georgia
United States	Birmingham, Alabama	Birmingham	Alabama
United States	Boca Raton, Florida	Boca Raton	Florida
United States	Boston, Massachusettes	Boston	Massachusetts
United States	Burlington, Vermont	Burlington	Vermont
United States	Chicago, Illinois	Chicago	Illinois
United States	Cincinnati, Ohio	Cincinnati	Ohio
United States	Cleveland, Ohio	Cleveland	Ohio
United States	Columbus, Ohio	Columbus	Ohio
United States	Coral Springs, Florida	Coral Springs	Florida
United States	Durham, North Carolina	Durham	North Carolina
United States	East Lansing, Michigan	East Lansing	Michigan
United States	Englewood, Colorado	Englewood	Colorado
United States	Fountain Valley, California	Fountain Valley	California
United States	Fresno, California	Fresno	California
United States	Georgetown, Texas	Georgetown	Texas
United States	Houston, Texas	Houston	Texas
United States	Kansas City	Kansas City	Kansas
United States	Kirkland, Washington	Kirkland	Washington
United States	Las Vegas, Nevada	Las Vegas	Nevada
United States	Little Rock, Arkansas	Little Rock	Arkansas
United States	Los Angeles, California	Los Angeles	California
United States	Lubbock, Texas	Lubbock	Texas
United States	Maitland, Florida	Maitland	Florida
United States	Memphis, Tennessee	Memphis	Tennessee
United States	Ocala, Florida	Ocala	Florida
United States	Pasadena, California	Pasadena	California
United States	Philadelphia, Pennsylvania	Philadelphia	Pennsylvania
United States	Port Orange, Florida	Port Orange	Florida
United States	Richmond, Virginia	Richmond	Virginia
United States	Richmond, Virginia	Richmond	Virginia
United States	Round Rock, Texas	Round Rock	Texas
United States	Scarborough, Maine	Scarborough	Maine
United States	Syracuse, New York	Syracuse	New York
United States	Tampa, Florida	Tampa	Florida
United States	Toledo, Ohio	Toledo	Ohio
United States	Virginia Beach, Virginia	Virginia Beach	Virginia
United States	Winfield, Illinois	Winfield	Illinois
United States	Winter Park, Florida	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cerevel Therapeutics, LLC

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Poland,  Serbia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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