Idiopathic Parkinson's Disease
Conditions
Keywords
Motor fluctuations, Off time, On time, Dyskinesia
Brief summary
Phase 3, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 3-arm safety and efficacy study (Part A) with an open-label phase (Part B).
Detailed description
During Part A, each patient will participate for up to 30 weeks, which includes a Screening Period of 1 to ≤ 6 weeks, followed by a Baseline Visit and 24 weeks of double-blind treatment: * Screening Period: 1 - 6 weeks. * Double-Blind Treatment Period: 24 weeks. After completion of Part A, patients will continue in Part B for an additional 56 weeks: * Open-Label Treatment Period: 52 weeks. * Post-Treatment Safety Follow Up: 4 weeks.
Interventions
DRUGtozadenant
DRUGplacebo
Sponsors
Biotie Therapies Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patient understands study requirements and has given his/her written informed consent on an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved consent form. * Parkinson's disease diagnosis consistent with UK Parkinson's Disease Society Brain Bank Diagnostic criteria * Minimum of 3 years since diagnosis. * Meet Hoehn and Yahr PD stage * Good response to levodopa * Stable regimen of anti-PD medications * Patients must have been taking a levodopa-containing anti-PD medication continuously for at least the previous 12 months * Patient has documented a minimum amount of Off time. * If of childbearing potential (male and female) must use an acceptable method of contraception
Exclusion criteria
* Previous tozadenant study participation * Current or recent participation in another study. * Secondary or atypical parkinsonism * Neurosurgical intervention for PD * Patient is taking apomorphine, budipine, istradefylline, tolcapone, or DUOPA™/Duodopa® * Treatment with excluded medications * Untreated or uncontrolled hyperthyroidism or hypothyroidism * Clinically significant out-of-range laboratory * MMSE out of range * Current episode of major depression (stable treatment for depression is permitted). * Recent suicide attempt or suicidal ideation type 4 or type 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) * Women lactating or pregnant * Hypersensitivity to any components of tozadenant or excipients * Abnormal findings on the physical or neurological examination, or medical history that would make the patient unsuitable for the study * History of hepatitis or cholangitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Baseline to 24 Weeks | Awake time in OFF state (hr) is the average of maximum of 3 days diary. The primary efficacy endpoint was the change from baseline to Week 24 in OFF time, where OFF time in the Hauser Parkinson's Disease Home Diary (PD) was averaged over 3 days prior to the study visit. During Screening and through Part A of the study, the Hauser Parkinson's Disease Home Diary (PD) was completed on specified days directly preceding the scheduled study visits/assessments. Motor activity was recorded as OFF, ON (mobility improved), or asleep time. Patients were asked to record ON time according to dyskinesia categories without dyskinesia, with non troublesome dyskinesia or with troublesome dyskinesia. Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Good ON Time From Baseline to Week 24 | Baseline to 24 Weeks | The first key secondary efficacy endpoint was the change from baseline to Week 24 in good ON which was defined as ON without dyskinesia or ON with non-troublesome dyskinesia. Awake Time in Good ON State (hr) is the average of a maximum of 3 days diary. Patients were asked to record ON time according to dyskinesia categories without dyskinesia, with non troublesome dyskinesia or with troublesome dyskinesia . Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep. For patients with missing baseline or baseline was measured post-dose, screening was used as baseline in the calculation of change from baseline. |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Baseline to Week 24 | The Unified Parkinson's Disease Rating Scale (UPDRS) is a scale to monitor Parkinson's Disease related disability and impairment. The scale itself has 4 components are titled; (1) nonmotor experiences of daily living (13 items), (2) motor experiences of daily living (13 items), (3) motor examination (18 items), and (4) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. In this outcome measure we are evaluating Part II and Part III. Part II: self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food Part III: clinician-scored monitored motor evaluation Range of score is 0 - 160: 0 meaning less impact and Higher score indicates greater impact of PD symptoms. |
| Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Baseline to Week 24 | Change from Baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III Motor Function (motor subscale) total scores. Each subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Range of score is 0 - 108. Higher scores indicate greater impact of PD symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) in the ON state was measured at a time representative of the ON state in that patient, not in best ON. Unified Parkinson's Disease Rating Scale Part III in OFF was not evaluated. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | At Week 24 | For the Clinical Global Impression of Improvement (CGI-I), the investigator or rater is asked to rate the patient's total improvement, whether or not in his or her judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale ranging from very much improved (1) to very much worse (7). A zero score is assigned if the score is not assessed. Scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Tables show Treatment vs Placebo. |
| Patient Global Impression of Improvement (PGI-I) Week 24 | At Week 24 | For the Patient Global Impression of Improvement (PG-I), the patient is asked to rate the total improvement of their Parkinson's Disease, whether or not in the patient's judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale. very much improved (1) to very much worse (7). A zero score is assigned if the score is not assessed. Scale: 1 = Normal, not at all ill, 2 = Borderline ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severly ill, 7 = Among the most extremely ill. Tables show Treatment vs Placebo. |
Countries
Austria, Canada, Czechia, Germany, Italy, Spain, United States
Participant flow
Recruitment details
This study was conducted at 80 sites in 7 countries. Planned patient enrollment numbers were achieved, but the study and the tozadenant development program were terminated prior to study completion by all patients, based on an unexpected emerging safety signal as discussed in the safety sections of this report.
Participants by arm
| Arm | Count |
|---|---|
| Tozadenant 60 mg BID During Part A, patients took two (2) tablets, one 60 mg tozadenant and one placebo, by mouth BID for a total of four (4) tablets per day. | 151 |
| Tozadenant 120 mg BID During Part A, patients took two (2) tablets of 60 mg tozadenant, by mouth BID for a total of four (4) tablets per day. | 149 |
| Placebo BID During Part A, patients took two (2) tablets of placebo, by mouth BID for a total of four (4) tablets per day. | 149 |
| Total | 449 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 22 | 30 | 15 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Sponsor Terminated by Investigator | 0 | 1 | 2 |
| Overall Study | Sponsor Terminated Study | 14 | 8 | 11 |
| Overall Study | Subject Terminated by Sponsor | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 9 | 9 |
Baseline characteristics
| Characteristic | Tozadenant 60 mg BID | Total | Placebo BID | Tozadenant 120 mg BID |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 78 Participants | 249 Participants | 83 Participants | 88 Participants |
| Age, Categorical Between 18 and 65 years | 73 Participants | 200 Participants | 66 Participants | 61 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8.68 | 64.7 years STANDARD_DEVIATION 8.19 | 65.0 years STANDARD_DEVIATION 8.29 | 65.1 years STANDARD_DEVIATION 7.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 15 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 146 Participants | 434 Participants | 144 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 148 Participants | 438 Participants | 146 Participants | 144 Participants |
| Region of Enrollment Austria | 3 participants | 8 participants | 2 participants | 3 participants |
| Region of Enrollment Canada | 5 participants | 15 participants | 5 participants | 5 participants |
| Region of Enrollment Czechia | 22 participants | 66 participants | 22 participants | 22 participants |
| Region of Enrollment Germany | 19 participants | 57 participants | 19 participants | 19 participants |
| Region of Enrollment Italy | 20 participants | 59 participants | 20 participants | 19 participants |
| Region of Enrollment Spain | 13 participants | 37 participants | 12 participants | 12 participants |
| Region of Enrollment United States | 69 participants | 207 participants | 69 participants | 69 participants |
| Sex: Female, Male Female | 51 Participants | 148 Participants | 48 Participants | 49 Participants |
| Sex: Female, Male Male | 100 Participants | 301 Participants | 101 Participants | 100 Participants |
| Weight at Screening | 78.74 kilograms STANDARD_DEVIATION 15.725 | 79.50 kilograms STANDARD_DEVIATION 15.585 | 79.35 kilograms STANDARD_DEVIATION 14.436 | 80.42 kilograms STANDARD_DEVIATION 16.576 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 150 | 1 / 149 | 1 / 148 |
| other Total, other adverse events | 115 / 150 | 111 / 149 | 111 / 148 |
| serious Total, serious adverse events | 13 / 150 | 12 / 149 | 15 / 148 |
Outcome results
Primary
Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time
Awake time in OFF state (hr) is the average of maximum of 3 days diary. The primary efficacy endpoint was the change from baseline to Week 24 in OFF time, where OFF time in the Hauser Parkinson's Disease Home Diary (PD) was averaged over 3 days prior to the study visit. During Screening and through Part A of the study, the Hauser Parkinson's Disease Home Diary (PD) was completed on specified days directly preceding the scheduled study visits/assessments. Motor activity was recorded as OFF, ON (mobility improved), or asleep time. Patients were asked to record ON time according to dyskinesia categories without dyskinesia, with non troublesome dyskinesia or with troublesome dyskinesia. Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep.
Time frame: Baseline to 24 Weeks
Population: Modified Intent-to-Treat (mITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 18 | 0.860 hours | Standard Deviation 2.4246 |
| Placebo BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 24 | -0.958 hours | Standard Deviation 2.2725 |
| Placebo BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 6 | -0.817 hours | Standard Deviation 2.0993 |
| Placebo BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Baseline | 6.34 hours | Standard Deviation 1.986 |
| Placebo BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 2 | -0.725 hours | Standard Deviation 2.0018 |
| Placebo BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 12 | -0.962 hours | Standard Deviation 2.2186 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Baseline | 6.00 hours | Standard Deviation 1.97 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 18 | -1.020 hours | Standard Deviation 2.5886 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 2 | -1.100 hours | Standard Deviation 2.1188 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 24 | -0.835 hours | Standard Deviation 2.973 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 12 | -1.460 hours | Standard Deviation 2.3689 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 6 | -1.112 hours | Standard Deviation 2.2903 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 24 | -1.789 hours | Standard Deviation 2.4802 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 2 | -1.409 hours | Standard Deviation 2.3957 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 18 | -1.742 hours | Standard Deviation 2.6855 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Baseline | 6.25 hours | Standard Deviation 2.337 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 6 | -1.879 hours | Standard Deviation 2.2866 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the Number of Hours Per Day Spent in OFF Time | Week 12 | -1.919 hours | Standard Deviation 2.2008 |
Secondary
Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl
Change from Baseline to Week 24 in the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III Motor Function (motor subscale) total scores. Each subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Range of score is 0 - 108. Higher scores indicate greater impact of PD symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) in the ON state was measured at a time representative of the ON state in that patient, not in best ON. Unified Parkinson's Disease Rating Scale Part III in OFF was not evaluated.
Time frame: Baseline to Week 24
Population: mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 24 | -2.15 score on a scale | Standard Deviation 6.363 |
| Placebo BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 18 | -2.46 score on a scale | Standard Deviation 6.112 |
| Placebo BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 6 | -2.29 score on a scale | Standard Deviation 5.011 |
| Placebo BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Baseline | 20.9 score on a scale | Standard Deviation 8.8 |
| Placebo BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 2 | -2.13 score on a scale | Standard Deviation 4.828 |
| Placebo BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 12 | -2.31 score on a scale | Standard Deviation 6.276 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Baseline | 19.8 score on a scale | Standard Deviation 8.58 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 6 | -2.18 score on a scale | Standard Deviation 5.476 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 18 | -2.64 score on a scale | Standard Deviation 6.303 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 24 | -2.13 score on a scale | Standard Deviation 6.822 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 2 | -2.35 score on a scale | Standard Deviation 5.144 |
| Tozadenant 60 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 12 | -2.69 score on a scale | Standard Deviation 5.822 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 24 | -2.93 score on a scale | Standard Deviation 6.048 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Baseline | 20.5 score on a scale | Standard Deviation 8.71 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 6 | -2.76 score on a scale | Standard Deviation 5.423 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 18 | -2.95 score on a scale | Standard Deviation 5.572 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 12 | -3.19 score on a scale | Standard Deviation 5.356 |
| Tozadenant 120 mg BID | Change From Baseline to Week 24 in the ON State in Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl | Week 2 | -2.83 score on a scale | Standard Deviation 4.613 |
Secondary
Change in Good ON Time From Baseline to Week 24
The first key secondary efficacy endpoint was the change from baseline to Week 24 in good ON which was defined as ON without dyskinesia or ON with non-troublesome dyskinesia. Awake Time in Good ON State (hr) is the average of a maximum of 3 days diary. Patients were asked to record ON time according to dyskinesia categories without dyskinesia, with non troublesome dyskinesia or with troublesome dyskinesia . Patients (and/or caregivers) were trained to complete the PD diary to record their status at half hourly intervals as OFF, ON without dyskinesia, ON with non troublesome dyskinesia, ON with troublesome dyskinesia, or asleep. For patients with missing baseline or baseline was measured post-dose, screening was used as baseline in the calculation of change from baseline.
Time frame: Baseline to 24 Weeks
Population: Modified Intent-to-Treat (mITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change in Good ON Time From Baseline to Week 24 | Week 2 | 0.790 hours | Standard Deviation 2.2778 |
| Placebo BID | Change in Good ON Time From Baseline to Week 24 | Week 18 | 0.709 hours | Standard Deviation 2.6284 |
| Placebo BID | Change in Good ON Time From Baseline to Week 24 | Week 6 | 0.812 hours | Standard Deviation 2.4177 |
| Placebo BID | Change in Good ON Time From Baseline to Week 24 | Week 24 | 1.011 hours | Standard Deviation 2.547 |
| Placebo BID | Change in Good ON Time From Baseline to Week 24 | Week 12 | 0.777 hours | Standard Deviation 2.43 |
| Placebo BID | Change in Good ON Time From Baseline to Week 24 | Baseline | 9.58 hours | Standard Deviation 2.266 |
| Tozadenant 60 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 2 | 1.145 hours | Standard Deviation 2.1291 |
| Tozadenant 60 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 12 | 1.307 hours | Standard Deviation 2.7051 |
| Tozadenant 60 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 6 | 1.002 hours | Standard Deviation 2.4533 |
| Tozadenant 60 mg BID | Change in Good ON Time From Baseline to Week 24 | Baseline | 9.92 hours | Standard Deviation 2.217 |
| Tozadenant 60 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 18 | 0.903 hours | Standard Deviation 2.6297 |
| Tozadenant 60 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 24 | 0.705 hours | Standard Deviation 3.1219 |
| Tozadenant 120 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 24 | 1.689 hours | Standard Deviation 2.7335 |
| Tozadenant 120 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 2 | 1.397 hours | Standard Deviation 2.5102 |
| Tozadenant 120 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 12 | 1.830 hours | Standard Deviation 2.287 |
| Tozadenant 120 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 6 | 1.650 hours | Standard Deviation 2.2538 |
| Tozadenant 120 mg BID | Change in Good ON Time From Baseline to Week 24 | Week 18 | 1.553 hours | Standard Deviation 2.6138 |
| Tozadenant 120 mg BID | Change in Good ON Time From Baseline to Week 24 | Baseline | 9.51 hours | Standard Deviation 2.554 |
Secondary
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function
The Unified Parkinson's Disease Rating Scale (UPDRS) is a scale to monitor Parkinson's Disease related disability and impairment. The scale itself has 4 components are titled; (1) nonmotor experiences of daily living (13 items), (2) motor experiences of daily living (13 items), (3) motor examination (18 items), and (4) motor complications (six items). Each subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. In this outcome measure we are evaluating Part II and Part III. Part II: self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food Part III: clinician-scored monitored motor evaluation Range of score is 0 - 160: 0 meaning less impact and Higher score indicates greater impact of PD symptoms.
Time frame: Baseline to Week 24
Population: mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 2 | -3.16 score on a scale | Standard Deviation 5.931 |
| Placebo BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 24 | -2.80 score on a scale | Standard Deviation 8.183 |
| Placebo BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 18 | -3.35 score on a scale | Standard Deviation 7.934 |
| Placebo BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 6 | -3.53 score on a scale | Standard Deviation 6.375 |
| Placebo BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Baseline | 33.2 score on a scale | Standard Deviation 12.14 |
| Placebo BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 12 | -3.02 score on a scale | Standard Deviation 8.385 |
| Tozadenant 60 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 24 | -2.54 score on a scale | Standard Deviation 8.584 |
| Tozadenant 60 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 2 | -3.43 score on a scale | Standard Deviation 6.611 |
| Tozadenant 60 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 12 | -3.64 score on a scale | Standard Deviation 7.393 |
| Tozadenant 60 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 18 | -3.63 score on a scale | Standard Deviation 7.958 |
| Tozadenant 60 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Baseline | 31.3 score on a scale | Standard Deviation 12.18 |
| Tozadenant 60 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 6 | -2.82 score on a scale | Standard Deviation 7.223 |
| Tozadenant 120 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 6 | -4.31 score on a scale | Standard Deviation 6.362 |
| Tozadenant 120 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 18 | -3.83 score on a scale | Standard Deviation 7.15 |
| Tozadenant 120 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 2 | -3.96 score on a scale | Standard Deviation 5.924 |
| Tozadenant 120 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Baseline | 32.3 score on a scale | Standard Deviation 12.08 |
| Tozadenant 120 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 12 | -4.38 score on a scale | Standard Deviation 6.602 |
| Tozadenant 120 mg BID | Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part II Activities of Daily Living (ADL) Subscale + Part III Motor Function | Week 24 | -3.68 score on a scale | Standard Deviation 7.853 |
Other Pre-specified
Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24
For the Clinical Global Impression of Improvement (CGI-I), the investigator or rater is asked to rate the patient's total improvement, whether or not in his or her judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale ranging from very much improved (1) to very much worse (7). A zero score is assigned if the score is not assessed. Scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. Tables show Treatment vs Placebo.
Time frame: At Week 24
Population: mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit. Patients were accounted for in the treatment group to which they were originally randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 2 | 3.5 score on a scale | Standard Deviation 0.8 |
| Placebo BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 12 | 3.5 score on a scale | Standard Deviation 0.98 |
| Placebo BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 18 | 3.5 score on a scale | Standard Deviation 1.04 |
| Placebo BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 24 | 3.5 score on a scale | Standard Deviation 0.92 |
| Placebo BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 6 | 3.4 score on a scale | Standard Deviation 0.86 |
| Tozadenant 60 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 18 | 3.5 score on a scale | Standard Deviation 0.92 |
| Tozadenant 60 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 2 | 3.4 score on a scale | Standard Deviation 0.87 |
| Tozadenant 60 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 12 | 3.3 score on a scale | Standard Deviation 1.01 |
| Tozadenant 60 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 6 | 3.3 score on a scale | Standard Deviation 0.96 |
| Tozadenant 60 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 24 | 3.5 score on a scale | Standard Deviation 1.07 |
| Tozadenant 120 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 6 | 3.2 score on a scale | Standard Deviation 0.93 |
| Tozadenant 120 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 24 | 3.2 score on a scale | Standard Deviation 0.98 |
| Tozadenant 120 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 18 | 3.2 score on a scale | Standard Deviation 0.97 |
| Tozadenant 120 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 12 | 3.2 score on a scale | Standard Deviation 0.92 |
| Tozadenant 120 mg BID | Global Assessments of Improvement: Clinical Global Impression of Improvement (CGI-I) Week 24 | Week 2 | 3.2 score on a scale | Standard Deviation 0.85 |
Other Pre-specified
Patient Global Impression of Improvement (PGI-I) Week 24
For the Patient Global Impression of Improvement (PG-I), the patient is asked to rate the total improvement of their Parkinson's Disease, whether or not in the patient's judgment it is due entirely to drug treatment, based on a 1-7 point weighted scale. very much improved (1) to very much worse (7). A zero score is assigned if the score is not assessed. Scale: 1 = Normal, not at all ill, 2 = Borderline ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severly ill, 7 = Among the most extremely ill. Tables show Treatment vs Placebo.
Time frame: At Week 24
Population: mITT population (Modified Intent-to-Treat) - all safety set patients who had valid diaries at baseline and had valid diaries on at least 1 post-baseline visit. Patients were accounted for in the treatment group to which they were originally randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 18 | 3.6 score on a scale | Standard Deviation 1.03 |
| Placebo BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 2 | 3.6 score on a scale | Standard Deviation 0.9 |
| Placebo BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 24 | 3.6 score on a scale | Standard Deviation 1.14 |
| Placebo BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 6 | 3.5 score on a scale | Standard Deviation 0.92 |
| Placebo BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 12 | 3.5 score on a scale | Standard Deviation 1.16 |
| Tozadenant 60 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 2 | 3.3 score on a scale | Standard Deviation 1.02 |
| Tozadenant 60 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 6 | 3.4 score on a scale | Standard Deviation 1.22 |
| Tozadenant 60 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 18 | 3.6 score on a scale | Standard Deviation 1.13 |
| Tozadenant 60 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 24 | 3.6 score on a scale | Standard Deviation 1.21 |
| Tozadenant 60 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 12 | 3.5 score on a scale | Standard Deviation 1.21 |
| Tozadenant 120 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 6 | 3.1 score on a scale | Standard Deviation 1.02 |
| Tozadenant 120 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 24 | 3.4 score on a scale | Standard Deviation 1.14 |
| Tozadenant 120 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 12 | 3.1 score on a scale | Standard Deviation 1.13 |
| Tozadenant 120 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 2 | 3.1 score on a scale | Standard Deviation 1 |
| Tozadenant 120 mg BID | Patient Global Impression of Improvement (PGI-I) Week 24 | Week 18 | 3.2 score on a scale | Standard Deviation 1.08 |