Parkinson Disease
Conditions
Keywords
Parkinsonian Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases
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.
Interventions
DRUGTavapadon
Participants will be randomized to receive tavapadon 5 mg QD to 15 mg QD tablet once daily orally for 27 weeks.
DRUGPlacebo
Participants will receive placebo matching to tavapadon QD orally for 27 weeks.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score | Week 26 | The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 2 and 3 combined is the sum of Part 2 score and Part 3 score at each assessment time for each participant. The combined score assesses 31 items with score range: 0-184. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders With Much Improved or Very Much Improved on Participant Global Impression of Change (PGIC) | Week 26 | The Patient Global Impression of Change (PGIC) is a 7-point response scale. The participant response to the question, Compared to your condition at the beginning of treatment, how much has your condition changed? was assessed. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome. |
| Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 5, 8, 11, 14, 18, 22, 26, and 27 | The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 2 and 3 combined is the sum of Part 2 score and Part 3 score at each assessment time for each participant. The combined score assesses 31 items with score range: 0-184. |
| Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 5, 8, 11, 14, 18, 22, 26, and 27 | The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 1, 2, and 3 combined is the sum of Part 1, Part 2, and Part 3 scores at each assessment time for each participant. The combined score assesses 44 items with score range: 0-236. |
| Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Week 5, 8, 11, 14, 18, 22, 26, and 27 | The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. |
| Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 5, 8, 11, 14, 18, 22, 26, and 27 | The Global Impression - Severity of Illness (CGI-S) Score is a clinician's impression of a participant's severity of illness on a 7-point scale. Scores ranged from 1-7 on a scale of 1 (normal) to 7 (among the most extremely ill participants). Higher values represent a worse outcome. |
| Change From Baseline in the MDS-UPDRS Part II Score | Week 26 | The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. |
| Change From Baseline in the PGIC Score | Week 5, 8, 11, 14, 18, 22, 26, and 27 | The Patient Global Impression of Change (PGIC) is a 7-point response scale. The participant response to the question, Compared to your condition at the beginning of treatment, how much has your condition changed? was assessed. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome. |
| Change From Baseline in the Epworth Sleepiness Scale (ESS) | Week 26 | The ESS is an 8-question, participant questionnaire 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 on a 4-point (0-3) scale with scores ranging from 0 (would never nod off) to 3 (high chance of nodding off). Higher values represent a worse outcome. A negative change from baseline represents an improvement in daytime sleepiness. The total ESS score range was 0 - 24. |
| Change From Baseline in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) | Week 26 | QUIP-RS is a questionnaire for impulse-compulsive disorders in Parkinson's disease rating scale to assess impulse control disorders (ICD). 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. A higher score indicating greater severity of symptoms. A negative change from baseline represents an improvement in ICDs. |
| Columbia-Suicide Severity Rating Scale (C-SSRS) | Week 27 | The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation (SI) categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose of study drug until 190 days following last dose of study drug. | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. |
| Clinical Global Impression - Improvement (CGI-I) Score | Week 5, 8, 11, 14, 18, 22, 26, and 27 | The Clinical Global Impression - Improvement (CGI-I) Score is a clinician's impression of how much the participant's illness has improved or worsened relative to the baseline on a 7-point scale. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome. |
Countries
Australia, France, Germany, Hungary, Italy, Poland, Serbia, South Korea, Spain, Taiwan, Thailand, Ukraine, United States
Participant flow
Pre-assignment details
In this Phase 3, Double-Blind study, a total of 304 participants with Parkinson's Disease (PD) were randomized in a 1:1 ratio to either Placebo, or tavapadon 5 mg to 15 mg once daily (QD) for 27 Weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching to Tavapadon tablet once daily (QD) orally for 27 weeks. | 153 |
| Tavapadon Participants received Tavapadon 5 mg to 15 mg tablet QD orally for 27 weeks. | 151 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 36 |
| Overall Study | Failure to Meet Continuation Criteria | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Non-Compliance with Study Drug | 0 | 1 |
| Overall Study | Other | 3 | 6 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Site Terminated by Sponsor | 1 | 3 |
| Overall Study | Treatment with Prohibited Concomitant Medications | 3 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Placebo | Tavapadon | Total |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.43 | 63.1 years STANDARD_DEVIATION 8.98 | 62.9 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 5 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 137 Participants | 141 Participants | 278 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 5 Participants | 10 Participants |
| MDS-UPDRS Score at Baseline (Parts II and III Combined) | 30.0 units on a scale STANDARD_DEVIATION 11.11 | 31.1 units on a scale STANDARD_DEVIATION 11.21 | 30.5 units on a scale STANDARD_DEVIATION 11.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 17 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 134 Participants | 134 Participants | 268 Participants |
| Sex: Female, Male Female | 68 Participants | 67 Participants | 135 Participants |
| Sex: Female, Male Male | 85 Participants | 84 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 151 |
| other Total, other adverse events | 59 / 153 | 99 / 151 |
| serious Total, serious adverse events | 2 / 153 | 7 / 151 |
Outcome results
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) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 2 and 3 combined is the sum of Part 2 score and Part 3 score at each assessment time for each participant. The combined score assesses 31 items with score range: 0-184.
Time frame: Week 26
Population: mITT Population includes subjects who receive at least 1 dose of study drug and have both a baseline and at least 1 postbaseline MDS-UPDRS assessment, and had available data for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score | -1.2 score on a scale | Standard Error 0.89 |
| Tavapadon | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score | -10.3 score on a scale | Standard Error 0.99 |
p-value: <0.000195% CI: [-11.7, -6.5]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score
The Global Impression - Severity of Illness (CGI-S) Score is a clinician's impression of a participant's severity of illness on a 7-point scale. Scores ranged from 1-7 on a scale of 1 (normal) to 7 (among the most extremely ill participants). Higher values represent a worse outcome.
Time frame: Week 5, 8, 11, 14, 18, 22, 26, and 27
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 5 | 0.0 score on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 8 | 0.0 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 18 | 0.0 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 14 | 0.0 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 22 | 0.0 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 11 | 0.0 score on a scale | Standard Error 0.05 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 26 | 0.0 score on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 27 | 0.0 score on a scale | Standard Error 0.05 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 27 | -0.3 score on a scale | Standard Error 0.06 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 8 | -0.2 score on a scale | Standard Error 0.05 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 11 | -0.3 score on a scale | Standard Error 0.06 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 26 | -0.4 score on a scale | Standard Error 0.06 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 14 | -0.3 score on a scale | Standard Error 0.05 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 18 | -0.3 score on a scale | Standard Error 0.06 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 22 | -0.4 score on a scale | Standard Error 0.06 |
| Tavapadon | Change From Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Week 5 | -0.2 score on a scale | Standard Error 0.05 |
Comparison: Wek 26p-value: <0.000195% CI: [-0.5, -0.2]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the Epworth Sleepiness Scale (ESS)
The ESS is an 8-question, participant questionnaire 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 on a 4-point (0-3) scale with scores ranging from 0 (would never nod off) to 3 (high chance of nodding off). Higher values represent a worse outcome. A negative change from baseline represents an improvement in daytime sleepiness. The total ESS score range was 0 - 24.
Time frame: Week 26
Population: FAS population includes all randomized participants who received at least 1 dose of study drug, and had available data for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Epworth Sleepiness Scale (ESS) | -0.1 score on a scale | Standard Error 0.22 |
| Tavapadon | Change From Baseline in the Epworth Sleepiness Scale (ESS) | -0.1 score on a scale | Standard Error 0.24 |
Comparison: Week 26p-value: 0.979595% CI: [-0.6, 0.6]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the MDS-UPDRS Part II Score
The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function.
Time frame: Week 26
Population: mITT Population includes subjects who receive at least 1 dose of study drug and have both a baseline and at least 1 postbaseline MDS-UPDRS assessment, and had available data for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the MDS-UPDRS Part II Score | 0.0 score on a scale | Standard Error 0.3 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Part II Score | -1.5 score on a scale | Standard Error 0.33 |
p-value: 0.000795% CI: [-2.4, -0.6]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the MDS-UPDRS Parts II and III Combined Score
The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 2 and 3 combined is the sum of Part 2 score and Part 3 score at each assessment time for each participant. The combined score assesses 31 items with score range: 0-184.
Time frame: Week 5, 8, 11, 14, 18, 22, 26, and 27
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 27 | -1.2 score on a scale | Standard Error 0.89 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 8 | -2.4 score on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 11 | -2.3 score on a scale | Standard Error 0.71 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 14 | -2.2 score on a scale | Standard Error 0.76 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 18 | -2.2 score on a scale | Standard Error 0.85 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 22 | -1.3 score on a scale | Standard Error 0.82 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 26 | -1.2 score on a scale | Standard Error 0.89 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 5 | -2.1 score on a scale | Standard Error 0.58 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 26 | -10.3 score on a scale | Standard Error 0.99 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 5 | -5.5 score on a scale | Standard Error 0.63 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 18 | -10.0 score on a scale | Standard Error 0.93 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 8 | -8.5 score on a scale | Standard Error 0.69 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 27 | -10.4 score on a scale | Standard Error 0.99 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 11 | -9.5 score on a scale | Standard Error 0.77 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 22 | -10.1 score on a scale | Standard Error 0.92 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts II and III Combined Score | Week 14 | -10.3 score on a scale | Standard Error 0.84 |
Comparison: Week 26p-value: <0.000195% CI: [-11.7, -6.5]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score
The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function. Parts 1, 2, and 3 combined is the sum of Part 1, Part 2, and Part 3 scores at each assessment time for each participant. The combined score assesses 44 items with score range: 0-236.
Time frame: Week 5, 8, 11, 14, 18, 22, 26, and 27
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 5 | -2.7 score on a scale | Standard Error 0.67 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 8 | -3.2 score on a scale | Standard Error 0.73 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 18 | -2.9 score on a scale | Standard Error 0.96 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 22 | -1.8 score on a scale | Standard Error 0.96 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 27 | -1.8 score on a scale | Standard Error 1.03 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 11 | -3.2 score on a scale | Standard Error 0.82 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 14 | -3.0 score on a scale | Standard Error 0.88 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 26 | -1.6 score on a scale | Standard Error 1.03 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 22 | -10.1 score on a scale | Standard Error 1.07 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 5 | -5.2 score on a scale | Standard Error 0.72 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 26 | -9.9 score on a scale | Standard Error 1.15 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 8 | -8.3 score on a scale | Standard Error 0.79 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 11 | -9.3 score on a scale | Standard Error 0.89 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 14 | -10.4 score on a scale | Standard Error 0.96 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 27 | -10.2 score on a scale | Standard Error 1.14 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Combined Score | Week 18 | -10.1 score on a scale | Standard Error 1.05 |
Comparison: Week 26p-value: <0.000195% CI: [-11.3, -5.3]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score
The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating tool was used to follow longitudinal course of Parkinson's Disease. It was made up of 4 parts: Part 1: Non-motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 2: Motor aspects of experiences of daily living (13 items. Score range: 0-52); Part 3: Motor examination (18 items. Score range: 0-132); Part 4: Motor complications (6 items. Score range: 0-24. Part 4 was not collected in this trial). Each item has 0-4 rating on scale from 0 (normal) to 4 (severe). Higher values represent a worse outcome. A negative change from baseline represents an improvement in motor function.
Time frame: Week 5, 8, 11, 14, 18, 22, 26, and 27
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 5 | -0.6 score on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 8 | -0.8 score on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 11 | -0.8 score on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 18 | -0.7 score on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 22 | -0.5 score on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 26 | -0.4 score on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 27 | -0.6 score on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 5 | -0.6 score on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 8 | -0.4 score on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 14 | -0.4 score on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 18 | -0.3 score on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 8 | -2.0 score on a scale | Standard Error 0.53 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 11 | -2.2 score on a scale | Standard Error 0.58 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 18 | -1.9 score on a scale | Standard Error 0.69 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 22 | -1.5 score on a scale | Standard Error 0.68 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 26 | -1.2 score on a scale | Standard Error 0.71 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 14 | -0.7 score on a scale | Standard Error 0.25 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 11 | -0.2 score on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 22 | 0.2 score on a scale | Standard Error 0.29 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 26 | 0.0 score on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 27 | 0.0 score on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 5 | -1.5 score on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 14 | -1.9 score on a scale | Standard Error 0.63 |
| Placebo | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 27 | -1.2 score on a scale | Standard Error 0.71 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 22 | -1.4 score on a scale | Standard Error 0.32 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 5 | 0.4 score on a scale | Standard Error 0.25 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 18 | -8.4 score on a scale | Standard Error 0.77 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 5 | -4.5 score on a scale | Standard Error 0.52 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 11 | 0.2 score on a scale | Standard Error 0.27 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 14 | -0.1 score on a scale | Standard Error 0.27 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 22 | -8.7 score on a scale | Standard Error 0.76 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 18 | -0.2 score on a scale | Standard Error 0.27 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 26 | -1.5 score on a scale | Standard Error 0.33 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 26 | -8.9 score on a scale | Standard Error 0.8 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 26 | 0.3 score on a scale | Standard Error 0.32 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 8 | 0.2 score on a scale | Standard Error 0.27 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 27 | 0.2 score on a scale | Standard Error 0.31 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 8 | -7.0 score on a scale | Standard Error 0.58 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 5 | -1.0 score on a scale | Standard Error 0.24 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part I: Week 22 | 0.0 score on a scale | Standard Error 0.3 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 8 | -1.5 score on a scale | Standard Error 0.25 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 14 | -1.7 score on a scale | Standard Error 0.29 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 27 | -1.3 score on a scale | Standard Error 0.34 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 18 | -1.5 score on a scale | Standard Error 0.3 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part II: Week 11 | -1.4 score on a scale | Standard Error 0.28 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 27 | -9.0 score on a scale | Standard Error 0.8 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 11 | -8.1 score on a scale | Standard Error 0.64 |
| Tavapadon | Change From Baseline in the MDS-UPDRS Parts I, II and III Individual Score | Part III: Week 14 | -8.6 score on a scale | Standard Error 0.69 |
Comparison: Part I: Week 26p-value: 0.076695% CI: [-0.1, 1.6]Mixed-effect Model Repeated Measurement
Comparison: Part II: Week 26p-value: 0.000795% CI: [-2.4, -0.6]Mixed-effect Model Repeated Measurement
Comparison: Part III: Week 26p-value: <0.000195% CI: [-9.7, -5.6]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the PGIC Score
The Patient Global Impression of Change (PGIC) is a 7-point response scale. The participant response to the question, Compared to your condition at the beginning of treatment, how much has your condition changed? was assessed. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome.
Time frame: Week 5, 8, 11, 14, 18, 22, 26, and 27
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the PGIC Score | Week 18 | 3.7 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the PGIC Score | Week 8 | 3.6 score on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the PGIC Score | Week 27 | 3.8 score on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in the PGIC Score | Week 11 | 3.6 score on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the PGIC Score | Week 22 | 3.7 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the PGIC Score | Week 14 | 3.6 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in the PGIC Score | Week 26 | 3.8 score on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in the PGIC Score | Week 5 | 3.5 score on a scale | Standard Error 0.08 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 26 | 2.8 score on a scale | Standard Error 0.12 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 18 | 2.9 score on a scale | Standard Error 0.12 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 22 | 2.9 score on a scale | Standard Error 0.12 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 27 | 2.8 score on a scale | Standard Error 0.12 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 5 | 3.3 score on a scale | Standard Error 0.09 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 8 | 3.1 score on a scale | Standard Error 0.09 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 11 | 3.1 score on a scale | Standard Error 0.1 |
| Tavapadon | Change From Baseline in the PGIC Score | Week 14 | 2.9 score on a scale | Standard Error 0.11 |
Comparison: Week 26p-value: <0.000195% CI: [-1.3, -0.7]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
QUIP-RS is a questionnaire for impulse-compulsive disorders in Parkinson's disease rating scale to assess impulse control disorders (ICD). 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. A higher score indicating greater severity of symptoms. A negative change from baseline represents an improvement in ICDs.
Time frame: Week 26
Population: FAS population includes all randomized participants who received at least 1 dose of study drug, and had available data for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) | -1.9 score on a scale | Standard Error 0.31 |
| Tavapadon | Change From Baseline in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) | -2.0 score on a scale | Standard Error 0.34 |
Comparison: Week 26p-value: 0.891695% CI: [-0.9, 0.8]Mixed-effect Model Repeated Measurement
Secondary
Clinical Global Impression - Improvement (CGI-I) Score
The Clinical Global Impression - Improvement (CGI-I) Score is a clinician's impression of how much the participant's illness has improved or worsened relative to the baseline on a 7-point scale. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome.
Time frame: Week 5, 8, 11, 14, 18, 22, 26, and 27
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 14 | 3.6 units on a scale | Standard Error 0.08 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 5 | 3.6 units on a scale | Standard Error 0.06 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 8 | 3.5 units on a scale | Standard Error 0.07 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 11 | 3.5 units on a scale | Standard Error 0.08 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 18 | 3.7 units on a scale | Standard Error 0.09 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 22 | 3.6 units on a scale | Standard Error 0.09 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 26 | 3.7 units on a scale | Standard Error 0.1 |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Score | Week 27 | 3.7 units on a scale | Standard Error 0.09 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 27 | 2.8 units on a scale | Standard Error 0.11 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 18 | 2.8 units on a scale | Standard Error 0.1 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 5 | 3.3 units on a scale | Standard Error 0.07 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 26 | 2.7 units on a scale | Standard Error 0.11 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 8 | 3.1 units on a scale | Standard Error 0.08 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 22 | 2.8 units on a scale | Standard Error 0.1 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 11 | 3.0 units on a scale | Standard Error 0.09 |
| Tavapadon | Clinical Global Impression - Improvement (CGI-I) Score | Week 14 | 2.9 units on a scale | Standard Error 0.09 |
Comparison: Week 26p-value: <0.000195% CI: [-1.3, -0.7]Mixed-effect Model Repeated Measurement
Secondary
Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation (SI) categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.
Time frame: Week 27
Population: FAS population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Any Suicidal Ideations | 0 Participants |
| Placebo | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Any Suicidal Behaviors | 0 Participants |
| Placebo | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Any Suicidal Behaviors or Ideations | 0 Participants |
| Placebo | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Non-Suicidal Self-Injurious Behavior | 0 Participants |
| Tavapadon | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Non-Suicidal Self-Injurious Behavior | 0 Participants |
| Tavapadon | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Any Suicidal Ideations | 5 Participants |
| Tavapadon | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Any Suicidal Behaviors or Ideations | 5 Participants |
| Tavapadon | Columbia-Suicide Severity Rating Scale (C-SSRS) | Participants With Any Suicidal Behaviors | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Time frame: From first dose of study drug until 190 days following last dose of study drug.
Population: FAS Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 84 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TESAE | 2 Participants |
| Tavapadon | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TESAE | 7 Participants |
| Tavapadon | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 115 Participants |
Secondary
Percentage of Responders With Much Improved or Very Much Improved on Participant Global Impression of Change (PGIC)
The Patient Global Impression of Change (PGIC) is a 7-point response scale. The participant response to the question, Compared to your condition at the beginning of treatment, how much has your condition changed? was assessed. Scores ranged from 1-7 on a scale of 1 (very much improved) to 7 (very much worse). Higher values represent a worse outcome.
Time frame: Week 26
Population: mITT Population includes subjects who receive at least 1 dose of study drug and have both a baseline and at least 1 postbaseline PGIC assessment, and had available data for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Percentage of Responders With Much Improved or Very Much Improved on Participant Global Impression of Change (PGIC) | 25 Participants |
| Tavapadon | Percentage of Responders With Much Improved or Very Much Improved on Participant Global Impression of Change (PGIC) | 46 Participants |
p-value: <0.000195% CI: [2.209, 7.037]Mixed Models Analysis