Flexible-Dose Trial in Early Parkinson's Disease (PD) (TEMPO-2)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04223193 |
|
Recruitment Status :
Recruiting
First Posted : January 10, 2020
Last Update Posted : February 25, 2021
|
Sponsor:
Cerevel Therapeutics, LLC
Information provided by (Responsible Party):
Cerevel Therapeutics, LLC
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Parkinson Disease | Drug: Tavapadon Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 296 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 in Early Parkinson's Disease (TEMPO-2 Trial) |
| Actual Study Start Date : | January 6, 2020 |
| Estimated Primary Completion Date : | November 30, 2022 |
| Estimated Study Completion Date : | November 30, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Parkinson disease
MedlinePlus related topics:
Parkinson's Disease
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Tavapadon
Participants will receive tavapadon tablet titrated up to 15 milligram (mg) once daily (QD) orally for 27 weeks.
|
Drug: Tavapadon
Participants will be randomized to receive tavapadon 5 mg QD to 15 mg QD tablet once daily orally for 27 weeks.
Other Names:
|
|
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 :
- Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score [ Time Frame: Up to 27 weeks ]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.
Secondary Outcome Measures :
- Percentage of Responders with "Much Improved" or "Very Much Improved" on Participant Global Impression of Change (PGIC ) [ Time Frame: Up to 27 weeks ]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.
- Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Combined 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 combined score will be assessed.
- 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 29 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.
- Change from Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score [ Time Frame: Up to 27 weeks ]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.
- Clinical Global Impression - Improvement (CGI-I) Score [ Time Frame: Up to 27 weeks ]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.
- Patient Global Impression of Change (PGIC) Score [ Time Frame: Up to 27 weeks ]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.
- Epworth Sleepiness Scale (ESS) [ Time Frame: Up to 27 weeks ]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.
- Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) [ Time Frame: Up to 27 weeks ]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.
- Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 27 weeks ]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).
- Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 31 Weeks ]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.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| 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 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 1, 1.5, or 2
- Participants with disease duration (from time of diagnosis) of <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 less than (<) 3 months in total but not within 2 months of signing the ICF. Prior and concurrent use of MAO-B inhibitors is permitted if use was initiated greater than (>) 90 days before signing of the ICF and the dosage will remain stable for the duration of the trial (no change in the Monoamine oxidase B (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
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 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.
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): NCT04223193
Locations
Show 41 study locations
Sponsors and Collaborators
Cerevel Therapeutics, LLC
Investigators
| Study Director: | Matthew Leoni, MD | Cerevel Therapeutics, LLC |
| Responsible Party: | Cerevel Therapeutics, LLC |
| ClinicalTrials.gov Identifier: | NCT04223193 |
| Other Study ID Numbers: |
CVL-751-PD-002 2019-002950-22 ( EudraCT Number ) |
| First Posted: | January 10, 2020 Key Record Dates |
| Last Update Posted: | February 25, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
Parkinson Disease Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases |
Central Nervous System Diseases Nervous System Diseases Movement Disorders Neurodegenerative Diseases |