Parkinson Disease
Conditions
Keywords
Parkinsonian Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Disease, Movement Disorders, Neurodegenerative Diseases
Brief summary
The purpose of this study is to assess the effect of tavapadon on the change from baseline in total daily hours of on time without troublesome dyskinesia in L-Dopa-treated participants with Parkinson's Disease (PD) who are experiencing motor fluctuations.
Interventions
DRUGTavapadon
Participants will be randomized to receive tavapadon 5 to 15 mg tablet QD 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 this 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 2, 2.5, or 3 in the on state. * Participants with a good response to levodopa (L- Dopa) in the judgment of the investigator. * Participants who return a completed self-reported home diary for motor function status (Hauser diary) during the screening period (after diary training and concordance testing has occurred), with recordings for 2 consecutive days (ie, 2 consecutive 24-hour periods) showing at least 2 and half hours of off time on each of the 2 days. * Participants who are on a stable dose of L-Dopa for at least 4 weeks prior to screening and are taking a minimum total daily dose of 400 milligram (mg) divided in at least 4 doses per day of standard carbidopa/levodopa or divided in at least 3 doses per day of extended-release carbidopa/levodopa capsules. The carbidopa/levodopa dose and frequency must be maintained for the duration of the trial. * Prior and concurrent use of catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidaseB (MAO-B) inhibitors, amantadine, istradefylline or anticholinergic drugs are permitted if the use was initiated greater than (\>) 90 days before the baseline visit and the dosage will remain stable for the duration of the trial (ie, no change in the COMT,MAO-B inhibitor, amantadine, istradefylline or anticholinergic dose is permitted during 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 supranuclear 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 Columbia-Suicide Severity Rating Scale (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 last6 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 5C-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 6months (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 12months. 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-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 aQTcF 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 Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 26 | The Hauser diary 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. The total on time without troublesome dyskinesia will be assessed and reported at endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 26 | The Hauser diary 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. The total daily Off time will be assessed and reported at endpoint. |
| Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 2, 5, 8, 11, 14, 18, 22, and 26 | The Hauser diary 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. The total on time without troublesome dyskinesia will be assessed and reported at different time points. |
| Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Week 26 | The 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. |
Countries
Australia, Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Serbia, Spain, Ukraine, United States
Participant flow
Recruitment details
In this Phase 3, Double-Blind study, a total of 368 subjects with Parkinson's Disease(PD) were be randomized in a 1:1 ratio to receive Tavapadon (5 mg to 15 mg) or Placebo once daily (QD) for 27 Weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will receive placebo matching to tavapadon tablet QD orally for 27 weeks.
Placebo: Participants will receive placebo matching to tavapadon QD orally for 27 weeks. | 255 |
| Tavapadon Participants will receive a tavapadon tablet titrated 5 to 15milligrams (mg) once daily (QD)orally for 27 weeks.
Tavapadon: Participants will be randomized to receive tavapadon 5 to 15 mg tablet QD orally for 27 weeks. | 252 |
| Total | 507 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 43 |
| Overall Study | Failure to Meet Continuation Criteria | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 2 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Non-Compliance with Study Drug | 0 | 2 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Site Terminated by Sponsor | 3 | 5 |
| Overall Study | Treatment with Prohibited Concomitant Medications | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 33 |
Baseline characteristics
| Characteristic | Placebo | Tavapadon | Total |
|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8.52 | 65.6 years STANDARD_DEVIATION 8.42 | 64.9 years STANDARD_DEVIATION 8.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 11 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 232 Participants | 226 Participants | 458 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 15 Participants | 22 Participants |
| Movement Disorder Society - Unified Parkinson's Disease Rating Score at Baseline (Parts I, II, III) Part I | 7.5 units on a scale STANDARD_DEVIATION 4.93 | 8.0 units on a scale STANDARD_DEVIATION 5.13 | 7.7 units on a scale STANDARD_DEVIATION 5.03 |
| Movement Disorder Society - Unified Parkinson's Disease Rating Score at Baseline (Parts I, II, III) Part II | 12.5 units on a scale STANDARD_DEVIATION 7.05 | 13.3 units on a scale STANDARD_DEVIATION 6.54 | 12.9 units on a scale STANDARD_DEVIATION 6.8 |
| Movement Disorder Society - Unified Parkinson's Disease Rating Score at Baseline (Parts I, II, III) Part III | 32.4 units on a scale STANDARD_DEVIATION 14.26 | 32.6 units on a scale STANDARD_DEVIATION 14.34 | 32.5 units on a scale STANDARD_DEVIATION 14.29 |
| OFF Time (hours) at Baseline | 5.408 hours STANDARD_DEVIATION 2.484 | 5.638 hours STANDARD_DEVIATION 2.246 | 5.523 hours STANDARD_DEVIATION 2.369 |
| ON Time (hours) Without Troublesome Dyskinesia at Baseline | 10.148 hours STANDARD_DEVIATION 2.637 | 9.884 hours STANDARD_DEVIATION 2.569 | 10.016 hours STANDARD_DEVIATION 2.604 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 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 | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 245 Participants | 246 Participants | 491 Participants |
| Sex: Female, Male Female | 85 Participants | 101 Participants | 186 Participants |
| Sex: Female, Male Male | 170 Participants | 151 Participants | 321 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 255 | 1 / 252 |
| other Total, other adverse events | 90 / 255 | 130 / 252 |
| serious Total, serious adverse events | 14 / 255 | 17 / 252 |
Outcome results
Primary
Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary)
The Hauser diary 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. The total on time without troublesome dyskinesia will be assessed and reported at endpoint.
Time frame: Week 26
Population: Population includes subjects who received at least one dose of study drug and had available data for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | 0.619 hours | Standard Error 0.188 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | 1.721 hours | Standard Error 0.207 |
p-value: <0.000195% CI: [0.553, 1.653]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score
The MDS-UPDRS 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.
Time frame: Week 26
Population: Population includes subjects who received at least one dose of study drug and had available data for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Part I | 0.0 units on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Part II | -0.1 units on a scale | Standard Error 0.35 |
| Placebo | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Part III | -4.6 units on a scale | Standard Error 0.65 |
| Tavapadon | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Part I | 0.4 units on a scale | Standard Error 0.3 |
| Tavapadon | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Part II | -1.4 units on a scale | Standard Error 0.39 |
| Tavapadon | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III Individual Score | Part III | -7.0 units on a scale | Standard Error 0.71 |
Comparison: Part Ip-value: 0.326595% CI: [-0.4, 1.2]Mixed-effect Model Repeated Measurement
Comparison: Part IIp-value: 0.020395% CI: [-2.2, -0.2]Mixed-effect Model Repeated Measurement
Comparison: Part IIIp-value: 0.011895% CI: [-4.3, -0.5]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary)
The Hauser diary 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. The total on time without troublesome dyskinesia will be assessed and reported at different time points.
Time frame: Week 2, 5, 8, 11, 14, 18, 22, and 26
Population: Population includes subjects who received at least one dose of study drug and had available data for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 2 | 0.535 hours | Standard Error 0.133 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 5 | 0.516 hours | Standard Error 0.148 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 8 | 0.470 hours | Standard Error 0.162 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 11 | 0.705 hours | Standard Error 0.163 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 14 | 0.584 hours | Standard Error 0.175 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 18 | 0.623 hours | Standard Error 0.174 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 22 | 0.870 hours | Standard Error 0.177 |
| Placebo | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 26 | 0.619 hours | Standard Error 0.188 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 26 | 1.721 hours | Standard Error 0.207 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 2 | 0.305 hours | Standard Error 0.133 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 14 | 1.282 hours | Standard Error 0.187 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 5 | 0.616 hours | Standard Error 0.151 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 22 | 1.749 hours | Standard Error 0.19 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 8 | 1.052 hours | Standard Error 0.168 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 18 | 1.592 hours | Standard Error 0.185 |
| Tavapadon | Change From Baseline in the Total On Time Without Troublesome Dyskinesia Based on the 2-day Average of the Self-completed Home Diary for Motor Function Status (Hauser Diary) | Week 11 | 1.063 hours | Standard Error 0.171 |
Comparison: Week 2p-value: 0.221695% CI: [-0.6, 0.139]Mixed-effect Model Repeated Measurement
Comparison: Week 5p-value: 0.637995% CI: [-0.316, 0.515]Mixed-effect Model Repeated Measurement
Comparison: Week 8p-value: 0.013295% CI: [0.122, 1.042]Mixed-effect Model Repeated Measurement
Comparison: Week 11p-value: 0.129995% CI: [-0.106, 0.821]Mixed-effect Model Repeated Measurement
Comparison: Week 14p-value: 0.006895% CI: [0.194, 1.202]Mixed-effect Model Repeated Measurement
Comparison: Week 18p-value: 0.000295% CI: [0.469, 1.469]Mixed-effect Model Repeated Measurement
Comparison: Week 22p-value: 0.000895% CI: [0.369, 1.389]Mixed-effect Model Repeated Measurement
Comparison: Week 26p-value: <0.000195% CI: [0.553, 1.653]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary)
The Hauser diary 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. The total daily Off time will be assessed and reported at endpoint.
Time frame: Week 26
Population: Population includes subjects who received at least one dose of study drug and had available data for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | -0.933 hours | Standard Error 0.182 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | -1.876 hours | Standard Error 0.2 |
p-value: 0.000695% CI: [-1.475, -0.41]Mixed-effect Model Repeated Measurement
Secondary
Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary)
The Hauser diary 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. The total daily Off time will be assessed and reported at different time points.
Time frame: Week 2, 5, 8, 11, 14, 18, 22, and 26
Population: Population includes subjects who received at least one dose of study drug and had available data for analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 2 | -0.598 hours | Standard Error 0.127 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 5 | -0.612 hours | Standard Error 0.144 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 8 | -0.549 hours | Standard Error 0.153 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 11 | -0.876 hours | Standard Error 0.156 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 14 | -0.779 hours | Standard Error 0.173 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 18 | -0.786 hours | Standard Error 0.176 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 22 | -1.014 hours | Standard Error 0.179 |
| Placebo | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 26 | -0.933 hours | Standard Error 0.182 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 26 | -1.876 hours | Standard Error 0.2 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 2 | -0.490 hours | Standard Error 0.127 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 14 | -1.682 hours | Standard Error 0.185 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 5 | -0.849 hours | Standard Error 0.146 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 22 | -1.993 hours | Standard Error 0.191 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 8 | -1.367 hours | Standard Error 0.159 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 18 | -1.810 hours | Standard Error 0.187 |
| Tavapadon | Change From Baseline in Total Daily Off Time Based on the 2-Day Average of the Self-Completed Home Diary for Motor Function Status (Hauser Diary) | Week 11 | -1.629 hours | Standard Error 0.164 |
Comparison: Week 2p-value: 0.547195% CI: [-0.245, 0.461]Mixed-effect Model Repeated Measurement
Comparison: Week 5p-value: 0.248895% CI: [-0.64, 0.166]Mixed-effect Model Repeated Measurement
Comparison: Week 8p-value: 0.000295% CI: [-1.252, -0.384]Mixed-effect Model Repeated Measurement
Comparison: Week 11p-value: 0.00195% CI: [-1.199, -0.307]Mixed-effect Model Repeated Measurement
Comparison: Week 14p-value: 0.000495% CI: [-1.403, -0.405]Mixed-effect Model Repeated Measurement
Comparison: Week 18p-value: <0.000195% CI: [-1.528, -0.52]Mixed-effect Model Repeated Measurement
Comparison: Week 22p-value: 0.000295% CI: [-1.493, -0.465]Mixed-effect Model Repeated Measurement
Comparison: Week 26p-value: 0.000695% CI: [-1.475, -0.41]Mixed-effect Model Repeated Measurement