TEMPO-4: Open-label Trial in Parkinson's Disease (PD)
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Up to 62 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.
- Number of Participants Who Discontinued Study Treatment [Up to 62 weeks]
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.
- Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS) [Up to 58 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.
- Epworth Sleepiness Scale (ESS) [Up to 58 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 participant may need to get more sleep, improve sleep practices, or seek medical attention to determine why he or she is sleepy.
- Columbia-Suicide Severity Rating Scale (C-SSRS) [Up to 60 weeks]
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).
- Study Medication Withdrawal Questionnaire (SMWQ) [Up to 60 weeks]
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.
- Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III [Up to 60 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 Hauser diary [Up to 58 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.
- Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Index [Baseline (Day 1), Weeks 32 and 58]
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.
- Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scores (VAS) [Baseline (Day 1), Weeks 32 and 58]
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).
Eligibility Criteria
Criteria
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 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.
De novo participant are eligible for the study if they met the following 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, with bradykinesia and motor asymmetry.
-
Participants with modified Hoehn and Yahr stage 1, 1.5, 2, 2.5, or 3.
-
Participants must be receiving some form of levodopa/carbidopa at the Screening Visit and must continue to use levodopa/carbidopa for the duration of the trial.
-
Prior and concurrent use catechol-O-methyl transferase (COMT) Inhibitor, Monoamine Oxidase B (MAO-B) Inhibitors, amantadine, or anticholinergic drugs are permitted.
-
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:
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.
De novo participants are excluded from the trial if any of the following criteria met:
-
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 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 judgment 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 less than (<) 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham, Alabama | Birmingham | Alabama | United States | 35233 |
| 2 | Scottsdale, Arizona | Scottsdale | Arizona | United States | 85258 |
| 3 | Little Rock, Arkansas | Little Rock | Arkansas | United States | 72205 |
| 4 | Fresno, California | Fresno | California | United States | 93710 |
| 5 | Pasadena, California | Pasadena | California | United States | 91105 |
| 6 | Reseda, California | Reseda | California | United States | 91335 |
| 7 | Englewood, Colorado | Englewood | Colorado | United States | 80113 |
| 8 | Boca Raton, Florida | Boca Raton | Florida | United States | 33486 |
| 9 | Coral Springs, Florida | Coral Springs | Florida | United States | 33067 |
| 10 | Lady Lake, Florida | Lady Lake | Florida | United States | 32159 |
| 11 | Maitland, Florida | Maitland | Florida | United States | 32751 |
| 12 | Naples, Florida | Naples | Florida | United States | 34102 |
| 13 | Ocala, Florida | Ocala | Florida | United States | 34470 |
| 14 | Tampa, Florida | Tampa | Florida | United States | 33615 |
| 15 | Chicago, Illinois | Chicago | Illinois | United States | 60612 |
| 16 | Winfield, Illinois | Winfield | Illinois | United States | 60190 |
| 17 | Scarborough, Maine | Scarborough | Maine | United States | 04074 |
| 18 | Lawrence, Massachusetts | Lawrence | Massachusetts | United States | 01843 |
| 19 | North Dartmouth, Massachusetts | North Dartmouth | Massachusetts | United States | 02747 |
| 20 | West Bloomfield, Michigan | West Bloomfield | Michigan | United States | 48322 |
| 21 | Toms River, New Jersey | Toms River | New Jersey | United States | 08755 |
| 22 | Albany, New York | Albany | New York | United States | 12208 |
| 23 | Asheville, North Carolina | Asheville | North Carolina | United States | 28806 |
| 24 | Durham, North Carolina | Durham | North Carolina | United States | 27705 |
| 25 | Dayton, Ohio | Dayton | Ohio | United States | 45459 |
| 26 | Toledo, Ohio | Toledo | Ohio | United States | 43614 |
| 27 | Rock Hill, South Carolina | Rock Hill | South Carolina | United States | 29732 |
| 28 | Georgetown, Texas | Georgetown | Texas | United States | 78626 |
| 29 | Houston, Texas | Houston | Texas | United States | 77030 |
| 30 | Houston, Texas | Houston | Texas | United States | 77030 |
| 31 | Lubbock, Texas | Lubbock | Texas | United States | 79410 |
| 32 | Round Rock, Texas | Round Rock | Texas | United States | 78681 |
| 33 | Burlington, Vermont | Burlington | Vermont | United States | 05401 |
| 34 | Richmond, Virginia | Richmond | Virginia | United States | 23229 |
| 35 | Richmond, Virginia | Richmond | Virginia | United States | 23233 |
| 36 | Virginia Beach, Virginia | Virginia Beach | Virginia | United States | 23456 |
| 37 | Kirkland, Washington | Kirkland | Washington | United States | 98034 |
| 38 | Spokane, Washington | Spokane | Washington | United States | 99202 |
| 39 | Erina, New South Wales | Erina | New South Wales | Australia | 2250 |
| 40 | Woolloongabba, Queensland | Woolloongabba | Queensland | Australia | 4102 |
| 41 | Clayton, Victoria | Clayton | Victoria | Australia | 3168 |
| 42 | Parkville, Victoria | Parkville | Victoria | Australia | 3050 |
| 43 | Chocen | Choceň | Chocen | Czechia | 56501 |
| 44 | Rychnov nad Kněžnou | Rychnov Nad Kněžnou | Czechia | 516 01 | |
| 45 | Creteil, | Créteil | Creteil | France | 94010 |
| 46 | Nîmes cedex 09 | Nîmes cedex 09 | France | 30029 | |
| 47 | Gera | Gera | Germany | D-07551 | |
| 48 | Haag in Oberbayern | Haag In Oberbayern | Germany | 83527 | |
| 49 | München | München | Germany | 81675 | |
| 50 | Milano | Milano | Italy | 20132 | |
| 51 | Rome | Rome | Italy | 00163 | |
| 52 | Katowice | Katowice | Poland | 40-097 | |
| 53 | Katowice | Katowice | Poland | 40-123 | |
| 54 | Warsaw | Warsaw | Poland | 01-868 | |
| 55 | Elche | Elche | Alicante | Spain | 03203 |
| 56 | Barcelona | Barcelona | Spain | 08035 | |
| 57 | Barcelona | Barcelona | Spain | 08041 | |
| 58 | Sant Cugat del Vallés Barcelona | Barcelona | Spain | 08190 | |
| 59 | Madrid | Madrid | Spain | 28006 | |
| 60 | Móstoles, Madrid | Madrid | Spain | 28938 | |
| 61 | Pamplona | Pamplona | Spain | 31008 | |
| 62 | San Sebastian | San Sebastian | Spain | 20009 | |
| 63 | Terrassa | Terrassa | Spain | 08222 | |
| 64 | Valencia | Valencia | Spain | 46026 |
Sponsors and Collaborators
- Cerevel Therapeutics, LLC
Investigators
- Study Director: Matthew Leoni, MD, Cerevel Therapeutics, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CVL-751-PD-004
- 2019-002952-17