Flexible-Dose Trial in Early Parkinson's Disease (PD)

Parkinson Disease Clinical Trial

— TEMPO-2  

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 in Early Parkinson's Disease (TEMPO-2 Trial)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04223193
• Other study ID #: CVL-751-PD-002
• Secondary ID: 2019-002950-22
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 6, 2020
• Est. completion date: November 2024

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 assess the efficacy, safety, tolerability and pharmacokinetics (PK) of flexible doses of tavapadon in participants with Parkinson's Disease.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 296
• Est. completion date: November 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• 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 the protocol.

• Participants with a diagnosis of PD that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria.

• 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 ICF.

• Participants with an MDS-UPDRS Part II score >=2 and Part III score >=10 at the Screening Visit and at the Baseline Visit.

• Participants with early PD who, in the opinion of the investigator, require pharmacologic intervention for disease management.

• Participants who are treatment naive or have a history of prior incidental treatment with dopaminergic agents (including L-Dopa and dopamine receptor agonist medications) for <3 months in total but not within 2 months of the Baseline Visit. Prior and concurrent use of MAO-B inhibitors is permitted if use was initiated >90 days before the Baseline Visit and the dosage will remain stable for the duration of the trial (ie, 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.

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 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 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 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 [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.

• 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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Tavapadon
Participants will be randomized to receive tavapadon 5 mg QD to 15 mg QD tablet once daily orally for 27 weeks.
• Placebo
Participants will receive placebo matching to tavapadon QD orally for 27 weeks.

Locations

Country	Name	City	State
Australia	Sydney, New South Wales	Sydney	New South Wales
France	Marseille, France	Marseille
France	Nantes CEDEX 1	Nantes
France	Toulouse Cedex 9	Toulouse
Germany	Berlin	Berlin
Germany	Bochum	Bochum
Germany	Gera	Gera
Germany	Muenchen	Muenchen
Hungary	Budapest	Budapest
Hungary	Pecs	Pécs
Hungary	Tatabanya	Tatabánya
Italy	Cassino	Cassino
Italy	Milano	Milano
Italy	Rome	Rome
Italy	Rozzano Milano	Rozzano
Italy	Torino	Torino
Korea, Republic of	Haeundae-gu, Busan	Busan	Haeundae-gu
Korea, Republic of	Dongdaemun-gu, Seoul	Seoul	Dongdaemun-gu
Korea, Republic of	Songpa-gu, Seoul	Seoul	Songpa-gu
Poland	Centrum Medyczne NEUROMED	Bydgoszcz
Poland	Cracow	Cracovia	Cracow
Poland	Katowice	Katowice
Poland	Centrum Medyczne Hope Clinic Sebastian Szklener	Lublin
Poland	Siemianowice Slaskie	Siemianowice Slaskie	Siemianowice Slaskie
Serbia	Belgrade	Belgrade
Spain	Barcelona	Barcelona
Spain	Móstoles, Madrid	Madrid
Taiwan	Zhongzheng, Taipei	Zhongzheng	Taipei
Taiwan	Zhongzheng, Taipei	Zhongzheng	Taipei
Thailand	Khlong Luang, Pathum Thani	Khlong Luang	Pathum Thani
Thailand	Nai Muang, Ubon Ratchathani	Nai Muang	Ubon Ratchathani
Thailand	Ratchathewi, Bangkok	Ratchathewi	Bangkok
Ukraine	Kiev	Kiev
Ukraine	Lviv	Lviv
Ukraine	Vinnitsa	Vinnitsa
United States	Albany, New York	Albany	New York
United States	Boca Raton, Florida	Boca Raton	Florida
United States	Cincinnati, Ohio	Cincinnati	Ohio
United States	Cleveland, Ohio	Cleveland	Ohio
United States	Cypress, Texas	Cypress	Texas
United States	Fresno, California	Fresno	California
United States	Houston, Texas	Houston	Texas
United States	Kirkland, Washington	Kirkland	Washington
United States	Lubbock, Texas	Lubbock	Texas
United States	Maitland, Florida	Maitland	Florida
United States	Memphis, Tennessee	Memphis	Tennessee
United States	Boston Neuro Research Center	North Dartmouth	Massachusetts
United States	Ocala, Florida	Ocala	Florida
United States	Richmond, Virginia	Richmond	Virginia
United States	Richmond, Virginia	Richmond	Virginia
United States	Round Rock, Texas	Round Rock	Texas
United States	Syracuse, New York	Syracuse	New York
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,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Poland,  Serbia,  Spain,  Taiwan,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	27 Weeks
Secondary	Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II 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. 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 total score range is 0-52. The higher the score the greater the severity. A negative change from baseline represents an improvement in motor function.	27 Weeks
Secondary	Percentage of Responders with "Much Improved" or "Very Much Improved" on Participant Global Impression of Change (PGIC )	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.	27 Weeks
Secondary	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.	27 Weeks
Secondary	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.	29 Weeks
Secondary	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.	27 Weeks
Secondary	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.	27 Weeks
Secondary	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.	27 Weeks
Secondary	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.	27 Weeks
Secondary	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.	27 Weeks
Secondary	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).	27 Weeks
Secondary	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.	31 Weeks