Early Parkinson's Disease
Conditions
Keywords
SPM 962, rotigotine, Parkinson's disease, monotherapy
Brief summary
To investigate superiority of SPM 962 over placebo in early Parkinson's disease patients in a multi-center, placebo-controlled, double-blind study following once-daily multiple transdermal doses of SPM 962 within a range of 4.5 to 36.0 mg (12-week dose titration/maintenance period)
Interventions
DRUGSPM 962
transdermal application, 1 time per day
DRUGplacebo
transdermal application, 1 time per day
Sponsors
Otsuka Pharmaceutical Co., Ltd.
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 79 Years
Healthy volunteers
No
Inclusion criteria
1. Subject diagnosed as having Parkinson's disease in accordance with Diagnostic Criteria established by the Research Committee of MHLW-specified Intractable Neurodegenerative Diseases (1995) 2. Subject is 30 years \< \> 80 years at the time of informed consent 3. Hoehn & Yahr stage 1- 3 4. Total of each sum score of UPDRS Part 2 and 3 is over 10 at screening test
Exclusion criteria
1. Subject has previously participated in a trial with SPM 962 2. Subject is on L-dopa treatment for total of over 6 months at the time of informed consent 3. Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening test and baseline 4. Subject has orthostatic hypotension 5. Subject has a history of epilepsy, convulsion and other 6. Subject has a complication of serious cardiac disorder/arrhythmia or has the history 7. Subject has arrhythmia and treated with class 1a anti-arrhythmic drugs (e.g. quinidine, procainamide etc.) or class 3 anti-arrhythmic drugs (e.g. amiodarone, sotalol etc.) 8. Subject has serious ECG abnormal at screening i.e.; 1) Subject has more than 450 msec of QTc values both in two measurements at screening test 2) Subject has more than 470 msec for females and more than 450 msec for males of mean QTc values of two measurements at baseline 9. Subject has congenital long QT syndrome 10. Subject has serum potassium of less than 3.5 mEq/L at screening test. 11. Subject has total bilirubin of 3.0 mg/dL and above or AST(GOT), ALT(GPT) greater than 2.5 times (or 100 IU/L and above) of the clinical laboratory's upper limit of the reference range at screening test 12. Subject has 30 mg/dL and above of BUN or 2.0 mg/dL and above of serum creatinine at screening test 13. Subject has a history of allergy to topical medicine, e.g. transdermal patch 14. Subject is pregnant, nursing, or is child bearing potential while the trial 15. Subject is receiving therapy with prohibited drug specified in the study protocol 16. Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal tissue transplant 17. Subject has dementia 18. Subject is unable to give consent 19. Subject is participating in another trial of an investigational drug or done so within 12 weeks prior to the initial treatment 20. Investigator judges that subject is inappropriate as a study subject with other reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End of Maintenance Period in Total of Each Sum Score of UPDRS Part 2 and Part 3 | baseline, end of maintenance period | Mean change (LOCF) from baseline to the end of maintenance period in total of each sum score of UPDRS Part 2 and Part 3. UPDRS is a scale for monitoring Parkinson's Disease-related disability and impairment. The UPDRS consists of the following four sub-scales. Part 1: Mentation, Part 2: Activities of Daily Living, Part 3: Motor, Part 4: Complications. Part 2 assesses 13 items and Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in UPDRS Part 2 Sum Score | Baseline, every two weeks | Mean change (LOCF) from baseline in UPDRS Part 2 sum score at every two weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. |
| Efficacy Rate in UPDRS Part 2 Sum Score | Baseline, every two weeks | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score at every two weeks after dosing. |
| UPDRS Part 3 Sum Score | Baseline, every two weeks | Mean change (LOCF) from baseline in UPDRS Part 3 sum score at every two weeks after dosing. UPDRS sub-scale Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. |
| Efficacy Rate in UPDRS Part 3 Sum Score | Baseline, every two weeks | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score at every two weeks after dosing. |
| Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3 | baseline, end of maintenance period | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in total of each sum score of UPDRS Part 2 and Part 3 at the end of maintenance period |
| UPDRS Part 4 Sum Score | Baseline, every two weeks | Mean change (LOCF) from baseline in UPDRS Part 4 sum score at every two weeks after dosing. UPDRS sub-scale Part 4 assesses 11 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. |
| Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Baseline, every two weeks | Mean change (LOCF) from baseline to the end of maintenance period in total of each sum score of UPDRS Part 1, 2, 3 and 4. UPDRS sub-scale Part 1, 2, 3, and 4 assess 4, 13, 14, and 11 items respectively. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. |
| The Modified Hoehn and Yahr Stage | Baseline, end of maintenance period | Mean change (LOCF) from baseline in the Modified Hoehn and Yahr Severity of Illness at the end of maintenance period. The Modified Hoehn and Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease without impairment of balance; 2.5, Mild bilateral disease with recovery on pull test; 3, Mild to moderate bilateral disease, some postural instability, physically independent 4, Severe disability, still able to walk or stand unassisted; and 5, Wheelchair bound or bedridden unless aided. |
| UPDRS Part 1 Sum Score | Baseline, every two weeks | MMean change (LOCF) from baseline in UPDRS Part 1 sum score at every two weeks after dosing. UPDRS sub-scale Part 1 assesses 4 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPM962 transdermal application of SPM962, 1 time per day | 88 |
| Placebo transdermal application of placebo, 1 time per day | 88 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | SPM962 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 53 Participants | 52 Participants | 105 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 36 Participants | 71 Participants |
| Age, Continuous | 66.2 years STANDARD_DEVIATION 7.9 | 65.1 years STANDARD_DEVIATION 8.1 | 65.6 years STANDARD_DEVIATION 8 |
| Region of Enrollment Japan | 88 participants | 88 participants | 176 participants |
| Sex: Female, Male Female | 51 Participants | 55 Participants | 106 Participants |
| Sex: Female, Male Male | 37 Participants | 33 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 90 | 55 / 90 |
| serious Total, serious adverse events | 2 / 90 | 0 / 90 |
Outcome results
Primary
Change From Baseline to the End of Maintenance Period in Total of Each Sum Score of UPDRS Part 2 and Part 3
Mean change (LOCF) from baseline to the end of maintenance period in total of each sum score of UPDRS Part 2 and Part 3. UPDRS is a scale for monitoring Parkinson's Disease-related disability and impairment. The UPDRS consists of the following four sub-scales. Part 1: Mentation, Part 2: Activities of Daily Living, Part 3: Motor, Part 4: Complications. Part 2 assesses 13 items and Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.
Time frame: baseline, end of maintenance period
Population: Full analysis set (FAS), last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPM962 | Change From Baseline to the End of Maintenance Period in Total of Each Sum Score of UPDRS Part 2 and Part 3 | -8.4 Scores on a scale | Standard Deviation 9.7 |
| Placebo | Change From Baseline to the End of Maintenance Period in Total of Each Sum Score of UPDRS Part 2 and Part 3 | -4.1 Scores on a scale | Standard Deviation 8.2 |
p-value: 0.00295% CI: [-3.7, 1.1]t-test, 2 sided
Secondary
Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3
Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in total of each sum score of UPDRS Part 2 and Part 3 at the end of maintenance period
Time frame: baseline, end of maintenance period
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM962 | Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3 | ≥20% decrease | 71.6 Percentage of participants |
| SPM962 | Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3 | ≥30% decrease | 55.7 Percentage of participants |
| Placebo | Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3 | ≥20% decrease | 40.9 Percentage of participants |
| Placebo | Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3 | ≥30% decrease | 29.5 Percentage of participants |
p-value: <0.00195% CI: [16.7, 44.6]Chi-squared, Corrected
p-value: <0.00195% CI: [12, 40.2]Chi-squared, Corrected
Secondary
Efficacy Rate in UPDRS Part 2 Sum Score
Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score at every two weeks after dosing.
Time frame: Baseline, every two weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (End of maintenance period) | 60.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 12) | 48.9 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 2) | 20.5 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 8) | 56.8 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 4) | 36.4 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 6) | 43.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 4) | 46.6 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 8) | 43.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 10) | 58.0 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 10) | 43.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 2) | 36.4 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 12) | 61.4 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (End of maintenance period) | 48.9 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 6) | 52.3 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (End of maintenance period) | 26.1 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 2) | 13.6 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 4) | 34.1 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 6) | 40.9 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 8) | 43.2 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 10) | 38.6 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (Week 12) | 39.8 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥20% decrease (End of maintenance period) | 39.8 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 2) | 13.6 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 6) | 28.4 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 8) | 25.0 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 10) | 29.5 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 12) | 26.1 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 2 Sum Score | ≥30% decrease (Week 4) | 19.3 Percentage of participants |
Secondary
Efficacy Rate in UPDRS Part 3 Sum Score
Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score at every two weeks after dosing.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 8) | 67.0 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 2) | 22.7 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 4) | 52.3 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 4) | 36.4 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 10) | 70.5 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 6) | 52.3 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 6) | 62.5 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 8) | 54.5 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 10) | 58.0 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 12) | 70.5 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 12) | 60.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 2) | 35.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (End of maintenance period) | 60.2 Percentage of participants |
| SPM962 | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (End of maintenance period) | 70.5 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (End of maintenance period) | 28.4 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 8) | 28.4 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 2) | 19.3 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 6) | 35.2 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 8) | 37.0 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 10) | 42.0 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 12) | 40.9 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (End of maintenance period) | 40.9 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 2) | 15.9 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 4) | 21.6 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 6) | 23.9 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 10) | 29.5 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥30% decrease (Week 12) | 28.4 Percentage of participants |
| Placebo | Efficacy Rate in UPDRS Part 3 Sum Score | ≥20% decrease (Week 4) | 28.4 Percentage of participants |
Secondary
Mean Change in UPDRS Part 2 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 2 sum score at every two weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.
Time frame: Baseline, every two weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | Week 12 | -1.8 Scores on a scale | Standard Deviation 3.2 |
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | End of maintenance period | -1.8 Scores on a scale | Standard Deviation 3.3 |
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | Week 4 | -1.2 Scores on a scale | Standard Deviation 2.7 |
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | Week 2 | -0.6 Scores on a scale | Standard Deviation 2.1 |
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | Week 6 | -1.6 Scores on a scale | Standard Deviation 2.9 |
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | Week 8 | -1.6 Scores on a scale | Standard Deviation 3.3 |
| SPM962 | Mean Change in UPDRS Part 2 Sum Score | Week 10 | -1.7 Scores on a scale | Standard Deviation 3.2 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | Week 12 | -1.1 Scores on a scale | Standard Deviation 2.9 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | End of maintenance period | -1.1 Scores on a scale | Standard Deviation 2.9 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | Week 6 | -1.4 Scores on a scale | Standard Deviation 2.1 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | Week 10 | -1.2 Scores on a scale | Standard Deviation 2.7 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | Week 8 | -1.3 Scores on a scale | Standard Deviation 2.4 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | Week 2 | -0.5 Scores on a scale | Standard Deviation 1.3 |
| Placebo | Mean Change in UPDRS Part 2 Sum Score | Week 4 | -1.0 Scores on a scale | Standard Deviation 1.9 |
Secondary
The Modified Hoehn and Yahr Stage
Mean change (LOCF) from baseline in the Modified Hoehn and Yahr Severity of Illness at the end of maintenance period. The Modified Hoehn and Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease without impairment of balance; 2.5, Mild bilateral disease with recovery on pull test; 3, Mild to moderate bilateral disease, some postural instability, physically independent 4, Severe disability, still able to walk or stand unassisted; and 5, Wheelchair bound or bedridden unless aided.
Time frame: Baseline, end of maintenance period
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM962 | The Modified Hoehn and Yahr Stage | Increased | 8.1 Percentage of participants |
| SPM962 | The Modified Hoehn and Yahr Stage | Not changed | 66.3 Percentage of participants |
| SPM962 | The Modified Hoehn and Yahr Stage | Decreased | 25.6 Percentage of participants |
| Placebo | The Modified Hoehn and Yahr Stage | Increased | 9.1 Percentage of participants |
| Placebo | The Modified Hoehn and Yahr Stage | Not changed | 71.6 Percentage of participants |
| Placebo | The Modified Hoehn and Yahr Stage | Decreased | 19.3 Percentage of participants |
Secondary
Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4
Mean change (LOCF) from baseline to the end of maintenance period in total of each sum score of UPDRS Part 1, 2, 3 and 4. UPDRS sub-scale Part 1, 2, 3, and 4 assess 4, 13, 14, and 11 items respectively. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 4 | -5.4 Scores on a scale | Standard Deviation 7.1 |
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 10 | -8.1 Scores on a scale | Standard Deviation 9.6 |
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 2 | -3.3 Scores on a scale | Standard Deviation 5.9 |
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 12 | -8.5 Scores on a scale | Standard Deviation 9.9 |
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 6 | -7.2 Scores on a scale | Standard Deviation 8.7 |
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | End of maintenance period | -8.5 Scores on a scale | Standard Deviation 9.9 |
| SPM962 | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 8 | -7.7 Scores on a scale | Standard Deviation 9.4 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | End of maintenance period | -4.1 Scores on a scale | Standard Deviation 8.5 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 2 | -2.1 Scores on a scale | Standard Deviation 4.6 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 4 | -3.8 Scores on a scale | Standard Deviation 5.8 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 8 | -4.6 Scores on a scale | Standard Deviation 7.6 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 10 | -4.7 Scores on a scale | Standard Deviation 7.7 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 12 | -4.1 Scores on a scale | Standard Deviation 8.5 |
| Placebo | Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Week 6 | -4.7 Scores on a scale | Standard Deviation 6.7 |
Secondary
UPDRS Part 1 Sum Score
MMean change (LOCF) from baseline in UPDRS Part 1 sum score at every two weeks after dosing. UPDRS sub-scale Part 1 assesses 4 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM962 | UPDRS Part 1 Sum Score | Week 4 | -0.17 Scores on a scale | Standard Deviation 0.75 |
| SPM962 | UPDRS Part 1 Sum Score | Week 2 | -0.17 Scores on a scale | Standard Deviation 0.46 |
| SPM962 | UPDRS Part 1 Sum Score | Week 6 | -0.14 Scores on a scale | Standard Deviation 0.89 |
| SPM962 | UPDRS Part 1 Sum Score | Week 8 | -0.23 Scores on a scale | Standard Deviation 0.89 |
| SPM962 | UPDRS Part 1 Sum Score | Week 10 | -0.25 Scores on a scale | Standard Deviation 0.91 |
| SPM962 | UPDRS Part 1 Sum Score | Week 12 | -0.25 Scores on a scale | Standard Deviation 0.91 |
| SPM962 | UPDRS Part 1 Sum Score | End of maintenance period | -0.25 Scores on a scale | Standard Deviation 0.91 |
| Placebo | UPDRS Part 1 Sum Score | End of maintenance period | -0.05 Scores on a scale | Standard Deviation 0.88 |
| Placebo | UPDRS Part 1 Sum Score | Week 8 | -0.07 Scores on a scale | Standard Deviation 0.56 |
| Placebo | UPDRS Part 1 Sum Score | Week 12 | -0.05 Scores on a scale | Standard Deviation 0.88 |
| Placebo | UPDRS Part 1 Sum Score | Week 2 | -0.01 Scores on a scale | Standard Deviation 0.28 |
| Placebo | UPDRS Part 1 Sum Score | Week 4 | -0.11 Scores on a scale | Standard Deviation 0.49 |
| Placebo | UPDRS Part 1 Sum Score | Week 10 | -0.11 Scores on a scale | Standard Deviation 0.63 |
| Placebo | UPDRS Part 1 Sum Score | Week 6 | -0.13 Scores on a scale | Standard Deviation 0.58 |
Secondary
UPDRS Part 3 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 3 sum score at every two weeks after dosing. UPDRS sub-scale Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM962 | UPDRS Part 3 Sum Score | Week 4 | -4.3 Scores on a scale | Standard Deviation 5.2 |
| SPM962 | UPDRS Part 3 Sum Score | Week 10 | -6.4 Scores on a scale | Standard Deviation 6.7 |
| SPM962 | UPDRS Part 3 Sum Score | Week 2 | -2.6 Scores on a scale | Standard Deviation 4.2 |
| SPM962 | UPDRS Part 3 Sum Score | Week 12 | -6.6 Scores on a scale | Standard Deviation 7.2 |
| SPM962 | UPDRS Part 3 Sum Score | Week 6 | -5.7 Scores on a scale | Standard Deviation 6.3 |
| SPM962 | UPDRS Part 3 Sum Score | End of maintenance period | -6.6 Scores on a scale | Standard Deviation 7.2 |
| SPM962 | UPDRS Part 3 Sum Score | Week 8 | -6.1 Scores on a scale | Standard Deviation 6.7 |
| Placebo | UPDRS Part 3 Sum Score | End of maintenance period | -3.0 Scores on a scale | Standard Deviation 6.2 |
| Placebo | UPDRS Part 3 Sum Score | Week 2 | -1.7 Scores on a scale | Standard Deviation 3.9 |
| Placebo | UPDRS Part 3 Sum Score | Week 4 | -2.7 Scores on a scale | Standard Deviation 4.7 |
| Placebo | UPDRS Part 3 Sum Score | Week 8 | -3.3 Scores on a scale | Standard Deviation 5.8 |
| Placebo | UPDRS Part 3 Sum Score | Week 10 | -3.4 Scores on a scale | Standard Deviation 5.8 |
| Placebo | UPDRS Part 3 Sum Score | Week 12 | -3.1 Scores on a scale | Standard Deviation 6.2 |
| Placebo | UPDRS Part 3 Sum Score | Week 6 | -3.3 Scores on a scale | Standard Deviation 5.3 |
Secondary
UPDRS Part 4 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 4 sum score at every two weeks after dosing. UPDRS sub-scale Part 4 assesses 11 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM962 | UPDRS Part 4 Sum Score | Week 10 | 0.19 Scores on a scale | Standard Deviation 0.62 |
| SPM962 | UPDRS Part 4 Sum Score | Week 2 | 0.19 Scores on a scale | Standard Deviation 0.45 |
| SPM962 | UPDRS Part 4 Sum Score | Week 4 | 0.28 Scores on a scale | Standard Deviation 0.79 |
| SPM962 | UPDRS Part 4 Sum Score | Week 6 | 0.18 Scores on a scale | Standard Deviation 0.54 |
| SPM962 | UPDRS Part 4 Sum Score | Week 8 | 0.20 Scores on a scale | Standard Deviation 0.61 |
| SPM962 | UPDRS Part 4 Sum Score | Week 12 | 0.18 Scores on a scale | Standard Deviation 0.64 |
| SPM962 | UPDRS Part 4 Sum Score | End of maintenance period | 0.18 Scores on a scale | Standard Deviation 0.64 |
| Placebo | UPDRS Part 4 Sum Score | Week 12 | 0.05 Scores on a scale | Standard Deviation 0.48 |
| Placebo | UPDRS Part 4 Sum Score | Week 6 | 0.03 Scores on a scale | Standard Deviation 0.39 |
| Placebo | UPDRS Part 4 Sum Score | Week 8 | 0.09 Scores on a scale | Standard Deviation 0.42 |
| Placebo | UPDRS Part 4 Sum Score | Week 2 | 0.09 Scores on a scale | Standard Deviation 0.33 |
| Placebo | UPDRS Part 4 Sum Score | Week 10 | 0.03 Scores on a scale | Standard Deviation 0.44 |
| Placebo | UPDRS Part 4 Sum Score | Week 4 | 0.08 Scores on a scale | Standard Deviation 0.38 |
| Placebo | UPDRS Part 4 Sum Score | End of maintenance period | 0.03 Scores on a scale | Standard Deviation 0.47 |