Dyskinesia, Levodopa Induced Dyskinesia (LID), Parkinson's Disease
Conditions
Keywords
Levodopa Induced Dyskinesia, LID, Parkinsonism
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled, 2-arm, parallel group study to evaluate the efficacy and safety of ADS-5102 extended release (ER) capsules, an investigational formulation of amantadine, dosed once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) maximal concentrations in the early morning through mid-day, when LID can be troublesome, and ii) lower concentrations in the evening, potentially reducing the negative impact of amantadine on sleep. This pharmacokinetic profile could enable higher doses to be tolerated with a once-nightly ER formulation than can be tolerated with an immediate-release formulation. The once-nightly dosing regimen may also provide enhanced convenience and compliance. In a previous clinical study, ADS-5102 met its primary endpoint; LID was significantly reduced as measured by the change in UDysRS score over 8 weeks vs. placebo.
Interventions
DRUGADS-5102
Oral capsules to be administered once nightly at bedtime, for 25 weeks
OTHERPlacebo
Oral capsules to be administered once nightly at bedtime, for 25 weeks
Sponsors
Adamas Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Signed a current IRB/REB/IEC-approved informed consent form * Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria * On a stable regimen of antiparkinson's medications for at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation * Following diary training, the subject is willing and able to understand and complete the 24-hour PD home diary (caregiver/study partner assistance allowed) * Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and subject must be willing to continue the same doses and regimens during study participation (this criterion does not apply to medications that are being taken pre-study only on an as-needed basis)
Exclusion criteria
* History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation) * History of seizures within 2 years prior to screening * History of stroke or transient ischemic attack (TIA) within 2 years prior to screening * History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer * Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening * If female, is pregnant or lactating * If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment. * Treatment with an investigational drug or device within 30 days prior to screening * Treatment with an investigational biologic within 6 months prior to screening * Current participation in another clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12 | Baseline to Week 12 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24 | Baseline to Week 24 | The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24. |
| Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Baseline (BL) to Week 12 (W12) and Week 24 (W24) | A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 8, 12, 18, and 24 visits. |
| Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | Baseline (BL) to Week 12 (W12) and Week 24 (W24) | The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each Part contains items or questions that were each rated on a scale from 0 (normal) to 4 (severe). The Combined Parts I, II, and III (representing the sum of the individual scores from Parts I, II, and III) has a scale range of 0-236. Higher scores, whether for individual Parts or the sum of the combined Parts, indicate more severe PD. |
| Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Baseline to Week 12 and Week 24 | The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement). The CGI-C was assessed at Baseline and Weeks 2, 8, 12, 18, and 24. |
Countries
Canada, United States
Participant flow
Recruitment details
126 Participants with Parkinson's disease (PD) and Levodopa-induced Dyskinesia (LID) were randomized at 41 study sites in the United States and Canada. The first subject was randomized on 20 May 2014 and the last subject completed on 18 November 2015.
Pre-assignment details
All randomized subjects who received ≥ 1 dose of study drug (123) were included in the Safety Analysis Population (60 placebo, 63 ADS-5102); all randomized subjects who received ≥ 1 dose of study drug and provided ≥ 1 postbaseline efficacy assessment (121) were included in the Modified Intent-to-Treat (MITT) population (58 placebo, 63 ADS-5102).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: oral capsules administered once nightly at bedtime for 25 weeks | 60 |
| ADS-5102 (340 mg) 340 mg dose of ADS-5102 (amantadine HCl extended release): oral capsules administered once nightly at bedtime for 25 weeks | 63 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Did Not Receive Study Drug | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Sponsor's Decision to Stop the Study | 7 | 7 |
| Overall Study | Subject Unwilling to Proceed | 7 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 10 |
Baseline characteristics
| Characteristic | Placebo | ADS-5102 (340 mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 31 Participants | 64 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 32 Participants | 59 Participants |
| Age, Continuous | 65.6 years STANDARD_DEVIATION 8.59 | 63.9 years STANDARD_DEVIATION 9.43 | 64.7 years STANDARD_DEVIATION 9.04 |
| Duration of Levodopa Treatment | 6.82 years STANDARD_DEVIATION 3.346 | 7.82 years STANDARD_DEVIATION 3.719 | 7.33 years STANDARD_DEVIATION 3.563 |
| Duration of LID | 3.21 years STANDARD_DEVIATION 2.491 | 4.05 years STANDARD_DEVIATION 3.085 | 3.64 years STANDARD_DEVIATION 2.831 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 3 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 60 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hoehn and Yahr Stage | 2.3 units on a scale STANDARD_DEVIATION 0.56 | 2.2 units on a scale STANDARD_DEVIATION 0.54 | 2.3 units on a scale STANDARD_DEVIATION 0.55 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Parts I, II, and III | 51.9 units on a scale STANDARD_DEVIATION 16.95 | 54.2 units on a scale STANDARD_DEVIATION 20.37 | 53.1 units on a scale STANDARD_DEVIATION 18.75 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I | 11.5 units on a scale STANDARD_DEVIATION 4.17 | 12.5 units on a scale STANDARD_DEVIATION 6.18 | 12.0 units on a scale STANDARD_DEVIATION 5.31 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II | 15.8 units on a scale STANDARD_DEVIATION 5.8 | 15.7 units on a scale STANDARD_DEVIATION 6.77 | 15.8 units on a scale STANDARD_DEVIATION 6.29 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | 24.6 units on a scale STANDARD_DEVIATION 12.1 | 25.9 units on a scale STANDARD_DEVIATION 14.49 | 25.3 units on a scale STANDARD_DEVIATION 13.34 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV | 11.3 units on a scale STANDARD_DEVIATION 2.36 | 11.8 units on a scale STANDARD_DEVIATION 2.95 | 11.6 units on a scale STANDARD_DEVIATION 2.68 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, Item 4.1 | 2.4 units on a scale STANDARD_DEVIATION 0.82 | 2.6 units on a scale STANDARD_DEVIATION 0.94 | 2.5 units on a scale STANDARD_DEVIATION 0.89 |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, Item 4.2 | 2.5 units on a scale STANDARD_DEVIATION 0.54 | 2.6 units on a scale STANDARD_DEVIATION 0.56 | 2.5 units on a scale STANDARD_DEVIATION 0.55 |
| PD Home Diary Asleep | 8.02 hours STANDARD_DEVIATION 1.446 | 7.78 hours STANDARD_DEVIATION 1.732 | 7.90 hours STANDARD_DEVIATION 1.597 |
| PD Home Diary Off | 2.94 hours STANDARD_DEVIATION 2.105 | 3.16 hours STANDARD_DEVIATION 2.372 | 3.05 hours STANDARD_DEVIATION 2.239 |
| PD Home Diary ON without Troublesome Dyskinesia | 8.59 hours STANDARD_DEVIATION 2.815 | 8.34 hours STANDARD_DEVIATION 3.466 | 8.46 hours STANDARD_DEVIATION 3.155 |
| PD Home Diary ON with Troublesome Dyskinesia | 4.46 hours STANDARD_DEVIATION 1.933 | 4.72 hours STANDARD_DEVIATION 2.537 | 4.59 hours STANDARD_DEVIATION 2.257 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 53 Participants | 60 Participants | 113 Participants |
| Sex: Female, Male Female | 23 Participants | 28 Participants | 51 Participants |
| Sex: Female, Male Male | 37 Participants | 35 Participants | 72 Participants |
| Subjects taking Antiparkinson Medication Anticholinergics | 3 Participants | 2 Participants | 5 Participants |
| Subjects taking Antiparkinson Medication COMT Inhibitor | 9 Participants | 7 Participants | 16 Participants |
| Subjects taking Antiparkinson Medication Dopamine Agonist | 34 Participants | 29 Participants | 63 Participants |
| Subjects taking Antiparkinson Medication Levodopa (Sinemet or Stalevo) | 60 Participants | 63 Participants | 123 Participants |
| Subjects taking Antiparkinson Medication MAO Inhibitors | 24 Participants | 26 Participants | 50 Participants |
| Time Since PD Diagnosis | 8.85 years STANDARD_DEVIATION 3.911 | 9.45 years STANDARD_DEVIATION 4.372 | 9.16 years STANDARD_DEVIATION 4.148 |
| Unified Dyskinesia Rating Scale (UDysRS) Total Objective Score (Parts III, IV) | 15.3 units on a scale STANDARD_DEVIATION 6.66 | 16.4 units on a scale STANDARD_DEVIATION 7.72 | 15.9 units on a scale STANDARD_DEVIATION 7.21 |
| Unified Dyskinesia Rating Scale (UDysRS) Total Score | 38.2 units on a scale STANDARD_DEVIATION 11.2 | 40.9 units on a scale STANDARD_DEVIATION 13.34 | 39.6 units on a scale STANDARD_DEVIATION 12.37 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 1 / 63 |
| other Total, other adverse events | 36 / 60 | 56 / 63 |
| serious Total, serious adverse events | 3 / 60 | 7 / 63 |
Outcome results
Primary
Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12
The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24.
Time frame: Baseline to Week 12
Population: MITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12 | -8.0 units on a scale | Standard Error 1.64 |
| ADS-5102 (340 mg) | Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 12 | -15.9 units on a scale | Standard Error 1.62 |
Comparison: 46 subjects per treatment arm provided 90% power using a 2-sided test at 5% significance.p-value: 0.000995% CI: [-12.5, -3.3]Linear Mixed Model w/ Repeated Measures
Secondary
Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24
The UDysRS is a dyskinesia rating scale from 0-104; it evaluates involuntary movements associated with PD. A higher score indicates more severe PD. The UDysRS was measured at Baseline and Weeks 2, 8, 12, 18, and 24.
Time frame: Baseline to Week 24
Population: MITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24 | -6.3 units on a scale | Standard Error 1.94 |
| ADS-5102 (340 mg) | Change From Baseline in the Unified Dyskinesia Rating Scale (UDysRS) Score at Week 24 | -15.6 units on a scale | Standard Error 1.87 |
p-value: 0.000895% CI: [-14.7, -4]Linear Mixed Model w/ Repeated Measures
Secondary
Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III)
The MDS-UPDRS Parts I, II, and III examined non-motor experiences of daily living, motor experiences of daily living, and motor examination, respectively. Each Part contains items or questions that were each rated on a scale from 0 (normal) to 4 (severe). The Combined Parts I, II, and III (representing the sum of the individual scores from Parts I, II, and III) has a scale range of 0-236. Higher scores, whether for individual Parts or the sum of the combined Parts, indicate more severe PD.
Time frame: Baseline (BL) to Week 12 (W12) and Week 24 (W24)
Population: MITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | Change from BL at Week 12 | -4.0 units on a scale | Standard Error 1.96 |
| Placebo | Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | Change from BL at Week 24 | -3.5 units on a scale | Standard Error 2.6 |
| ADS-5102 (340 mg) | Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | Change from BL at Week 12 | -5.2 units on a scale | Standard Error 1.92 |
| ADS-5102 (340 mg) | Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Combined Score (Parts I, II, and III) | Change from BL at Week 24 | -1.3 units on a scale | Standard Error 2.45 |
p-value: 0.683395% CI: [-6.6, 4.3]Linear Mixed Model w/ Repeated Measures
p-value: 0.555795% CI: [-5, 9.2]Linear Mixed Model w/ Repeated Measures
Secondary
Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time)
A PD home diary was used to score 5 different conditions in 30-minute intervals: ASLEEP, OFF, ON (ie, had adequate control of PD symptoms) without dyskinesia, ON with non-troublesome dyskinesia, and ON with troublesome dyskinesia. The results were based on 2 consecutive 24-hour diaries taken prior to the day of randomization and prior to the Week 2, 8, 12, 18, and 24 visits.
Time frame: Baseline (BL) to Week 12 (W12) and Week 24 (W24)
Population: MITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/o troublesome dyskinesia (W12) | 0.82 hours | Standard Error 0.432 |
| Placebo | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/o troublesome dyskinesia (W24) | 1.37 hours | Standard Error 0.456 |
| Placebo | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in OFF time (W12) | 0.32 hours | Standard Error 0.263 |
| Placebo | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in OFF time (W24) | 0.22 hours | Standard Error 0.282 |
| Placebo | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/ troublesome dyskinesia (W12) | -1.58 hours | Standard Error 0.358 |
| Placebo | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/ troublesome dyskinesia (W24) | -1.86 hours | Standard Error 0.38 |
| ADS-5102 (340 mg) | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/ troublesome dyskinesia (W12) | -3.12 hours | Standard Error 0.359 |
| ADS-5102 (340 mg) | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/o troublesome dyskinesia (W12) | 3.56 hours | Standard Error 0.434 |
| ADS-5102 (340 mg) | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in OFF time (W24) | -0.58 hours | Standard Error 0.268 |
| ADS-5102 (340 mg) | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/o troublesome dyskinesia (W24) | 3.59 hours | Standard Error 0.44 |
| ADS-5102 (340 mg) | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in ON time w/ troublesome dyskinesia (W24) | -3.31 hours | Standard Error 0.363 |
| ADS-5102 (340 mg) | Change in the Standardized PD Home Diary (ON Time Without Troublesome Dyskinesia, ON Time With Troublesome Dyskinesia, OFF Time) | Change in OFF time (W12) | -0.59 hours | Standard Error 0.265 |
p-value: <0.000195% CI: [1.53, 3.96]Linear Mixed Model w/ Repeated Measures
p-value: 0.000795% CI: [0.96, 3.47]Linear Mixed Model w/ Repeated Measures
p-value: 0.017195% CI: [-1.64, -0.16]Linear Mixed Model w/ Repeated Measures
p-value: 0.040695% CI: [-1.58, -0.04]Linear Mixed Model w/ Repeated Measures
p-value: 0.003195% CI: [-2.55, -0.53]Linear Mixed Model w/ Repeated Measures
p-value: 0.007295% CI: [-2.49, -0.4]Linear Mixed Model w/ Repeated Measures
Secondary
Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms
The CGI-C consisted of a single question that assessed the investigator's global impression of the subject's change from Baseline in overall PD symptoms, including but not limited to LID. The CGI-C required that the investigator rate the extent to which the subject's PD had improved or worsened (from marked worsening to marked improvement). The CGI-C was assessed at Baseline and Weeks 2, 8, 12, 18, and 24.
Time frame: Baseline to Week 12 and Week 24
Population: MITT population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | No Change | 25 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Marked Improvement | 5 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Marked Improvement | 2 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Moderate Improvement | 10 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Minimal Worsening | 10 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Minimal Improvement | 12 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Minimal Improvement | 10 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | No Change | 17 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Moderate Worsening | 2 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Moderate Improvement | 9 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Moderate Worsening | 4 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Marked Worsening | 0 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Marked Worsening | 0 Participants |
| Placebo | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Minimal Worsening | 6 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Marked Worsening | 2 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Marked Improvement | 18 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Moderate Improvement | 20 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Minimal Improvement | 13 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | No Change | 9 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Minimal Worsening | 2 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Moderate Worsening | 0 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 12 | Marked Worsening | 1 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Marked Improvement | 14 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Moderate Improvement | 17 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Minimal Improvement | 12 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | No Change | 7 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Minimal Worsening | 5 Participants |
| ADS-5102 (340 mg) | Clinician's Global Impression of Change (CGI-C) in Overall PD Symptoms | Week 24 | Moderate Worsening | 5 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.1071Cochran-Mantel-Haenszel