Parkinson's Disease
Conditions
Keywords
SPM 962, rotigotine, Parkinson's disease, concomitant use of L-dopa
Brief summary
* To investigate the safety of once-daily repeated transdermal administration of SPM 962 within a dose range of 4.5 to 36.0 mg/day (54-week treatment period) in Parkinson's disease (PD) patients treated concomitantly with L-dopa in a multi-center, open-label uncontrolled study. * To investigate efficacy of SPM 962 in an exploratory manner.
Interventions
DRUGSPM 962
SPM 962 transdermal patch once a daily up to 36.0 mg/day
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Subject completed the preceding trial 243-08-001.
Exclusion criteria
* Subject discontinued from the preceding trial 243-08-001. * Subject had a serious adverse event which association with the investigational drug was not ruled out during trial 243-08-001. * Subject has a persistent serious adverse event at the baseline, which was observed and association with the investigational drug was ruled out during trial 243-08-001. * Subject had persistent confusion, hallucination, delusion or excitation during trial 243-08-001. * Subject has abnormal behavior such as obsessive-compulsive disorder and delusion in 243-08-001 study. * Subject showed serious or extensive application site reactions beyond the application site in the 243-08-001 study. * Subject has orthostatic hypotension or a systolic blood pressure (SBP) \<= 100 mmHg and has a decrease of SBP from spine to standing position \>= 30 mmHg at baseline. * Subject has a history of epilepsy, convulsion etc. during trial 243-08-001. * Subject develops serious ECG abnormality at the baseline. * Subject has QTc-interval \>= 500 msec at the baseline or subject has an increase of QTc-interval \>= 60 msec from the baseline in the trial 243-08-001 and has a QTc-interval \> 470 msec in female or \> 450 msec in male at the baseline. * Subject had a serum potassium level \< 3.5 mEq/L at the end of the taper period in trial 243-08-001. * Subject has a total bilirubin \>= 3.0 mg/dL or AST(GOT) or ALT(GPT) greater than 2.5 times of the upper limit of the reference range (or ? 100 IU/L) at the end of the period in trial 243-08-001. * Subject had BUN \>= 30 mg/dL or serum creatinine \>= 2.0 mg/dl at the end of the taper period in trial 243-08-001. * Subject who plans pregnancy during the trial. * Subject is unable to give consent. * Subject is judged to be inappropriate for this trial by the investigator for the reasons other than above.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Up to 55 weeks after dosing | The safety of the long-term SPM 962 treatment was examined based on the incidence and severity of AEs, vital signs, and laboratory parameters. AEs of special interest (1-3) are defined as below: 1. sudden onset of sleep 2. obsessive-compulsive disorder or impulse-control disorder 3. hallucination, delusion Application site reaction is scored as -, ±, +, ++, +++, or ++++. More + indicates a greater severity of symptoms. The worst score obtained throughout the evaluation period was to be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| UPDRS Part 2 Sum Score (Average of on State and Off State) | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average of on state and off state). 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. |
| Absolute Time Spent Off | Baseline, up to 54 weeks after dosing | Mean number of hours in off state during a 24-hour period. |
| UPDRS Part 1 Sum Score | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 1 sum score. 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. |
| UPDRS Part 2 Sum Score (On State) | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (on state). A decrease in the scores means improvement. |
| UPDRS Part 2 Sum Score (Off State) | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (off state). A decrease in the scores means improvement. |
| UPDRS Part 4 Sum Score | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 4 sum score. 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 UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average of on State and Off State), UPDRS Part 3 Sum Score (on State), and UPDRS Part 4 Sum Score | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in total of UPDRS Part 1 sum score, UPDRS Part 2 sum score (average of on state and off state), UPDRS Part 3 sum score (on state), and UPDRS Part 4 sum score. A decrease in the scores means improvement. |
| Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Baseline, Up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 3 sum score (on state). 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 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. |
| Each Item of UPDRS Part 1 | Baseline, up to 54 weeks after dosing. | The percentage of subjects with elevated scores for each item of UPDRS Part 1. The data at week 52 is shown. |
| Each Item of UPDRS Part 2 (on State) | Baseline, up to 54 weeks after dosing. | The percentage of subjects with elevated scores for each item of UPDRS Part 2 (on state). The data at week 52 is shown. |
| Each Item of UPDRS Part 2 (Off State) | Baseline, up to 54 weeks after dosing. | The percentage of subjects with elevated scores for each item of UPDRS Part 2 (off state). The data at week 52 is shown. |
| Each Item of UPDRS Part 2 (Average of on State and Off State) | Baseline, up to 54 weeks after dosing. | The percentage of subjects with elevated scores for each item of UPDRS Part 2 (average of on state and off state). The data at week 52 is shown. |
| Total of UPDRS Part 2 Sum Score (Average of on State and Off State) and UPDRS Part 3 Sum Score (on State) | Baseline, up to 54 weeks after dosing | Mean change (LOCF) from baseline in total of UPDRS Part 2 sum score (average of on state and off state) and UPDRS Part 3 sum score (on state). A decrease in the scores means improvement. |
| Each Item of UPDRS Part 3 (on State) | Baseline, up to 54 weeks after dosing. | The percentage of subjects with elevated scores for each item of UPDRS Part 3 (on state). The data at week 52 is shown. |
| Each Item of UPDRS Part 4 | Baseline, up to 54 weeks after dosing. | The percentage of subjects with elevated scores for each item of UPDRS Part 4. The data at week 52 is shown. |
| The Modified Hoehn & Yahr Severity of Illness | Baseline, up to 54 weeks after dosing. | Change (LOCF) from baseline in the Modified Hoehn & Yahr Severity of Illness. The Modified Hoehn & 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. The data at week 52 is shown. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPM 962 SPM 962 transdermal patch | 321 |
| Total | 321 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 42 |
| Overall Study | Discontinuation criteria | 1 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | SPM 962 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 206 Participants |
| Age, Categorical Between 18 and 65 years | 115 Participants |
| Age, Continuous | 65.9 years STANDARD_DEVIATION 8.4 |
| Region of Enrollment Japan | 321 participants |
| Sex: Female, Male Female | 185 Participants |
| Sex: Female, Male Male | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 290 / 321 |
| serious Total, serious adverse events | 34 / 321 |
Outcome results
Primary
Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters
The safety of the long-term SPM 962 treatment was examined based on the incidence and severity of AEs, vital signs, and laboratory parameters. AEs of special interest (1-3) are defined as below: 1. sudden onset of sleep 2. obsessive-compulsive disorder or impulse-control disorder 3. hallucination, delusion Application site reaction is scored as -, ±, +, ++, +++, or ++++. More + indicates a greater severity of symptoms. The worst score obtained throughout the evaluation period was to be assessed.
Time frame: Up to 55 weeks after dosing
Population: Safety set (SS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Severe AEs | 16 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Discontinuation due to AEs | 47 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Sitting systolic blood pressure, ≤ 100 mmHg | 9 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | QTcB ≥ 500 ms | 5 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Any AEs | 311 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Treatment-related AEs | 269 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | SAEs | 34 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Treatment-related SAEs | 6 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Death | 1 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | AEs of special interest 1 | 7 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | AEs of special interest 2 | 4 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | AEs of special interest 3 | 54 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Valvular disease of the heart | 0 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | QTcF ≥ 500 ms | 2 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Application site reaction ≥ +++ | 14 participants |
| SPM 962 | Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | Weight decrease reported as AE | 8 participants |
Secondary
Absolute Time Spent Off
Mean number of hours in off state during a 24-hour period.
Time frame: Baseline, up to 54 weeks after dosing
Population: FAS subjects with measurable off time at baseline, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | Absolute Time Spent Off | Week 12 | -2.5 Hours | Standard Deviation 2.5 |
| SPM 962 | Absolute Time Spent Off | Week 24 | -2.5 Hours | Standard Deviation 2.7 |
| SPM 962 | Absolute Time Spent Off | Week 52 | -2.0 Hours | Standard Deviation 2.7 |
Secondary
Each Item of UPDRS Part 1
The percentage of subjects with elevated scores for each item of UPDRS Part 1. The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Each Item of UPDRS Part 1 | Intellectual impairment | 2.8 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 1 | Thought disorder | 9.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 1 | Depression | 5.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 1 | Motivation/Initiative | 4.4 Percentage of Participants |
Secondary
Each Item of UPDRS Part 2 (Average of on State and Off State)
The percentage of subjects with elevated scores for each item of UPDRS Part 2 (average of on state and off state). The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Sensory Complaints Related to Parkinsonism | 5.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Speech | 6.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Salivation | 13.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Swallowing | 7.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Handwriting | 12.1 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Cutting Food and Handling Utensils | 11.1 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Dressing | 9.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Hygiene | 10.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Turning in Bed / Adjusting Bed Clothes | 10.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Falling - Unrelated to Freezing | 9.9 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Freezing When Walking | 14.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Walking | 12.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Average of on State and Off State) | Tremor | 5.7 Percentage of Participants |
Secondary
Each Item of UPDRS Part 2 (Off State)
The percentage of subjects with elevated scores for each item of UPDRS Part 2 (off state). The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Speech | 5.8 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Salivation | 10.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Swallowing | 6.3 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Handwriting | 11.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Cutting Food and Handling Utensils | 11.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Dressing | 9.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Hygiene | 11.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Turning in Bed / Adjusting Bed Clothes | 10.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Falling - Unrelated to Freezing | 9.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Freezing When Walking | 17.9 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Walking | 13.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Tremor | 4.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (Off State) | Sensory Complaints Related to Parkinsonism | 5.8 Percentage of Participants |
Secondary
Each Item of UPDRS Part 2 (on State)
The percentage of subjects with elevated scores for each item of UPDRS Part 2 (on state). The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Speech | 4.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Salivation | 11.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Swallowing | 6.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Handwriting | 7.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Cutting Food and Handling Utensils | 6.9 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Dressing | 6.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Hygiene | 5.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Turning in Bed / Adjusting Bed Clothes | 7.9 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Falling - Unrelated to Freezing | 8.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Freezing When Walking | 6.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Walking | 8.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Tremor | 4.4 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 2 (on State) | Sensory Complaints Related to Parkinsonism | 3.5 Percentage of Participants |
Secondary
Each Item of UPDRS Part 3 (on State)
The percentage of subjects with elevated scores for each item of UPDRS Part 3 (on state). The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rapid Alternating Movements of Hands (Right) | 6.9 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Speech | 6.3 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Facial Expression | 5.4 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Tremor at Rest (Face, lips, chin) | 0.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Tremor at Rest (Left hand) | 1.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Tremor at Rest (Right hand) | 1.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Tremor at Rest (Left foot) | 2.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Tremor at Rest (Right foot) | 1.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Action or Postural Tremor of Hands (Left hand) | 5.4 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Action or Postural Tremor of Hands (Right hand) | 6.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rigidity (Neck) | 5.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rigidity (Left upper extremity) | 2.8 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Posture Erect | 11.4 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rigidity (Right upper extremity) | 2.8 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rigidity (Left lower extremity) | 5.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rigidity (Right lower extremity) | 4.1 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Finger Taps (Left) | 5.1 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Finger Taps (Right) | 5.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Hand Movements (Left) | 7.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Hand Movements (Right) | 6.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Rapid Alternating Movements of Hands (Left) | 7.3 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Leg Agility (Left) | 6.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Leg Agility (Right) | 7.3 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Arising From Chair | 9.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Gait | 9.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Postural Stability | 8.9 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 3 (on State) | Body Bradykinesia / Hypokinesia | 7.0 Percentage of Participants |
Secondary
Each Item of UPDRS Part 4
The percentage of subjects with elevated scores for each item of UPDRS Part 4. The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Each Item of UPDRS Part 4 | Duration | 15.1 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Disability | 5.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Painful Dyskinesias | 0.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Presence of Early Morning Dystonia | 2.5 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Are off periods predictable? | 3.2 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Are off periods unpredictable? | 1.6 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Do off periods come on suddenly? | 1.3 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Proportion of off in waking day | 5.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Patients with anorexia, nausea, or vomiting | 5.0 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Patients with any sleep disturbances | 10.7 Percentage of Participants |
| SPM 962 | Each Item of UPDRS Part 4 | Patient with symptomatic orthostasis | 1.9 Percentage of Participants |
Secondary
The Modified Hoehn & Yahr Severity of Illness
Change (LOCF) from baseline in the Modified Hoehn & Yahr Severity of Illness. The Modified Hoehn & 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. The data at week 52 is shown.
Time frame: Baseline, up to 54 weeks after dosing.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | The Modified Hoehn & Yahr Severity of Illness | Increased | 7.3 Percentage of participants |
| SPM 962 | The Modified Hoehn & Yahr Severity of Illness | Not changed | 62.5 Percentage of participants |
| SPM 962 | The Modified Hoehn & Yahr Severity of Illness | Decreased | 30.2 Percentage of participants |
Secondary
Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average of on State and Off State), UPDRS Part 3 Sum Score (on State), and UPDRS Part 4 Sum Score
Mean change (LOCF) from baseline in total of UPDRS Part 1 sum score, UPDRS Part 2 sum score (average of on state and off state), UPDRS Part 3 sum score (on state), and UPDRS Part 4 sum score. A decrease in the scores means improvement.
Time frame: Baseline, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average of on State and Off State), UPDRS Part 3 Sum Score (on State), and UPDRS Part 4 Sum Score | Week 12 | -11.4 Scores on a scale | Standard Deviation 9.7 |
| SPM 962 | Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average of on State and Off State), UPDRS Part 3 Sum Score (on State), and UPDRS Part 4 Sum Score | Week 24 | -11.1 Scores on a scale | Standard Deviation 10.5 |
| SPM 962 | Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average of on State and Off State), UPDRS Part 3 Sum Score (on State), and UPDRS Part 4 Sum Score | Week 52 | -9.7 Scores on a scale | Standard Deviation 12.1 |
Secondary
Total of UPDRS Part 2 Sum Score (Average of on State and Off State) and UPDRS Part 3 Sum Score (on State)
Mean change (LOCF) from baseline in total of UPDRS Part 2 sum score (average of on state and off state) and UPDRS Part 3 sum score (on state). A decrease in the scores means improvement.
Time frame: Baseline, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | Total of UPDRS Part 2 Sum Score (Average of on State and Off State) and UPDRS Part 3 Sum Score (on State) | Week 12 | -10.9 Scores on a scale | Standard Deviation 9.2 |
| SPM 962 | Total of UPDRS Part 2 Sum Score (Average of on State and Off State) and UPDRS Part 3 Sum Score (on State) | Week 24 | -10.5 Scores on a scale | Standard Deviation 9.9 |
| SPM 962 | Total of UPDRS Part 2 Sum Score (Average of on State and Off State) and UPDRS Part 3 Sum Score (on State) | Week 52 | -9.4 Scores on a scale | Standard Deviation 11.4 |
Secondary
Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 3 sum score (on state). 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 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, Up to 54 weeks after dosing
Population: Full analysis set (FAS), last observation carried forward (LOCF)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Week 12 | -8.3 Scores on a scale | Standard Deviation 7.1 |
| SPM 962 | Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Week 24 | -8.0 Scores on a scale | Standard Deviation 7.6 |
| SPM 962 | Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Week 52 | -7.5 Scores on a scale | Standard Deviation 8.6 |
Secondary
UPDRS Part 1 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 1 sum score. 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, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | UPDRS Part 1 Sum Score | Week 12 | -0.33 Scores on a scale | Standard Deviation 1.07 |
| SPM 962 | UPDRS Part 1 Sum Score | Week 24 | -0.25 Scores on a scale | Standard Deviation 1.17 |
| SPM 962 | UPDRS Part 1 Sum Score | Week 52 | -0.15 Scores on a scale | Standard Deviation 1.29 |
Secondary
UPDRS Part 2 Sum Score (Average of on State and Off State)
Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average of on state and off state). 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, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | UPDRS Part 2 Sum Score (Average of on State and Off State) | Week 12 | -2.6 Scores on a scale | Standard Deviation 3 |
| SPM 962 | UPDRS Part 2 Sum Score (Average of on State and Off State) | Week 24 | -2.5 Scores on a scale | Standard Deviation 3.4 |
| SPM 962 | UPDRS Part 2 Sum Score (Average of on State and Off State) | Week 52 | -1.9 Scores on a scale | Standard Deviation 4 |
Secondary
UPDRS Part 2 Sum Score (Off State)
Mean change (LOCF) from baseline in UPDRS Part 2 sum score (off state). A decrease in the scores means improvement.
Time frame: Baseline, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | UPDRS Part 2 Sum Score (Off State) | Week 12 | -3.7 Scores on a scale | Standard Deviation 4.3 |
| SPM 962 | UPDRS Part 2 Sum Score (Off State) | Week 24 | -3.8 Scores on a scale | Standard Deviation 4.8 |
| SPM 962 | UPDRS Part 2 Sum Score (Off State) | Week 52 | -2.5 Scores on a scale | Standard Deviation 5.5 |
Secondary
UPDRS Part 2 Sum Score (On State)
Mean change (LOCF) from baseline in UPDRS Part 2 sum score (on state). A decrease in the scores means improvement.
Time frame: Baseline, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | UPDRS Part 2 Sum Score (On State) | Week 12 | -1.9 Scores on a scale | Standard Deviation 2.8 |
| SPM 962 | UPDRS Part 2 Sum Score (On State) | Week 24 | -1.7 Scores on a scale | Standard Deviation 3 |
| SPM 962 | UPDRS Part 2 Sum Score (On State) | Week 52 | -1.3 Scores on a scale | Standard Deviation 3.7 |
Secondary
UPDRS Part 4 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 4 sum score. 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, up to 54 weeks after dosing
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | UPDRS Part 4 Sum Score | Week 12 | -0.24 Scores on a scale | Standard Deviation 1.29 |
| SPM 962 | UPDRS Part 4 Sum Score | Week 24 | -0.28 Scores on a scale | Standard Deviation 1.32 |
| SPM 962 | UPDRS Part 4 Sum Score | Week 52 | -0.13 Scores on a scale | Standard Deviation 1.42 |