Parkinson's Disease
Conditions
Keywords
SPM 962, rotigotine, Parkinson's disease, concomitant use of L-dopa
Brief summary
The primary objective of this study is to investigate safety of SPM 962 in advanced PD patients in a multi-center, open-label, non-controlled study following once-daily multiple transdermal doses of SPM962 within a range of 4.5 to 36.0 mg (maximum treatment period: 54 weeks). Efficacy is also to be exploratory investigated.
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 243-05-001.
Exclusion criteria
* Subject discontinued from the preceding trial 243-05-001. * Subject had a serious adverse event which association with the investigational drug was not ruled out during trial 243-05-001. * Subject has a persistent serious adverse event at the baseline, which was observed and association with the investigational drug was ruled out during trial 243-05-001. * Subject had persistent hallucination or delusion during trial 243-05-001. * Subject has psychiatric conditions such as confusion, excitation, delirium, abnormal behaviour at the baseline. * Subject has orthostatic hypotension at baseline. * Subject has a history of epilepsy, convulsion etc. during trial 243-05-001. * Subject has a complication of serious cardiac disorder. * Subject has arrhythmia and need to be treated with class 1a antiarrhythmic drugs (e.g. quinidine, procainamide etc.) or class 3 antiarrhythmic drugs (e.g. amiodarone, sotalol etc.). * 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 243-05-001 and has a QTc-interval \> 470 msec in female or \> 450 msec in male at the baseline. * Subject had hypokalaemia in 243-05-001 study and not yet recovered. * 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 243-05-001. * Subject has BUN \>= 25 mg/dL or serum creatinine \>= 2.0 mg/dl at the end of the taper period in trial 243-05-001. * Subject has a history of allergic reaction to topical agents such as transdermal patch. Subject showed serious or extensive application site reactions beyond the application site in the 243-05-001 study. * Subject who plans pregnancy during the trial. * Subject has dementia. * 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, Vital Signs, and Laboratory Parameters. | Up to 55 weeks after dosing | Incidence and severity of adverse events, vital signs, and laboratory parameters after dosing. \*decrease in difference between supine and standing systolic blood pressure |
| Skin Irritation Score of the Application Site | Up to 55 weeks after dosing | Skin irritation score of the application site were evaluated according to the criteria below. The worst score throughout the treatment period was used in the analysis. -: no reaction, ±: mild erythema, +: erythema, ++: erythema and Oedema, +++: erythema and oedema and rash papular, or serous papule, or vesicles, ++++: bullosum |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) up to 54 weeks after dosing 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. |
| UPDRS Part 2 Sum Score | Baseline, Up to 54 weeks after dosing | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) up to 54 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. |
| Absolute Time Spent Off | Up to 54 weeks after dosing | Mean number of hours in off state during a 24-hour period. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPM 962 SPM 962 : SPM 962 transdermal patch once a daily up to 36.0 mg/day | 130 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 25 |
| Overall Study | Lack of Efficacy | 5 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | SPM 962 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 96 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age, Continuous | 66.9 years STANDARD_DEVIATION 7.5 |
| Region of Enrollment Japan | 130 participants |
| Sex: Female, Male Female | 74 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 119 / 130 |
| serious Total, serious adverse events | 17 / 130 |
Outcome results
Primary
Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters.
Incidence and severity of adverse events, vital signs, and laboratory parameters after dosing. \*decrease in difference between supine and standing systolic blood pressure
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, Vital Signs, and Laboratory Parameters. | Any AEs | 126 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | Treatment-Related AEs | 112 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | SAEs including death | 17 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | Severe AEs | 12 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | Discontinuation due to AEs | 26 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | Severe laboratory abnormality | 10 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | ≥30 mmHg decrease* | 6 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | Treatment-related AE of orthostatic hypotension | 6 participants |
| SPM 962 | Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters. | QTcB ≥500 ms | 1 participants |
Primary
Skin Irritation Score of the Application Site
Skin irritation score of the application site were evaluated according to the criteria below. The worst score throughout the treatment period was used in the analysis. -: no reaction, ±: mild erythema, +: erythema, ++: erythema and Oedema, +++: erythema and oedema and rash papular, or serous papule, or vesicles, ++++: bullosum
Time frame: Up to 55 weeks after dosing
Population: SS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPM 962 | Skin Irritation Score of the Application Site | - | 18 participants |
| SPM 962 | Skin Irritation Score of the Application Site | ± | 53 participants |
| SPM 962 | Skin Irritation Score of the Application Site | + | 42 participants |
| SPM 962 | Skin Irritation Score of the Application Site | ++ | 9 participants |
| SPM 962 | Skin Irritation Score of the Application Site | +++ | 7 participants |
| SPM 962 | Skin Irritation Score of the Application Site | ++++ | 1 participants |
| SPM 962 | Skin Irritation Score of the Application Site | +++> | 8 participants |
Secondary
Absolute Time Spent Off
Mean number of hours in off state during a 24-hour period.
Time frame: Up to 54 weeks after dosing
Population: FAS subjects with off state at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | Absolute Time Spent Off | Week 12 | -3.0 Hours | Standard Deviation 2.7 |
| SPM 962 | Absolute Time Spent Off | Week 24 | -2.6 Hours | Standard Deviation 2.9 |
| SPM 962 | Absolute Time Spent Off | Week 52 | -1.9 Hours | Standard Deviation 3 |
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) up to 54 weeks after dosing 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 | -9.6 Scores on a scale | Standard Deviation 8.1 |
| SPM 962 | Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Week 24 | -9.1 Scores on a scale | Standard Deviation 8.2 |
| SPM 962 | Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Week 52 | -8.3 Scores on a scale | Standard Deviation 9.8 |
Secondary
UPDRS Part 2 Sum Score
Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) up to 54 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, Up to 54 weeks after dosing
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPM 962 | UPDRS Part 2 Sum Score | Week 12 | -2.7 Scores on a scale | Standard Deviation 3.5 |
| SPM 962 | UPDRS Part 2 Sum Score | Week 24 | -2.4 Scores on a scale | Standard Deviation 3.7 |
| SPM 962 | UPDRS Part 2 Sum Score | Week 52 | -1.9 Scores on a scale | Standard Deviation 4.7 |