A Placebo- and Ropinirole-Controlled Study for SPM 962 in Advanced Parkinson's Disease Patients

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01628926
• Collaborator: (none)
• Enrollment: 420
• Locations: 8
• Arms: 3
• Duration (Months): 23
• Patients Per Site: 52.5
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

• To demonstrate the non-inferiority of SPM 962 to ropinirole in terms of efficacy in order to confirm clinical value of SPM 962.

• To demonstrate the superiority of SPM 962 to placebo in terms of efficacy.

• To investigate the tolerability and safety of SPM 962 up to 36.0 mg/day.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: SPM 962; Drug: Ropinirole; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 420 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, 3-Arm, Parallel Group, Placebo- and Ropinirole-Controlled Study for SPM 962 in Advanced Parkinson's Disease Patients With Concomitant Treatment of L-dopa
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPM 962 SPM 962 transdermal patch	Drug: SPM 962; SPM 962 transdermal patch once a daily up to 36.0 mg/day
Active Comparator: Ropinirole Ropinirole tablet	Drug: Ropinirole; Ropinirole oral administration TID up to 15.0 mg/day
Placebo Comparator: Placebo SPM962 placebo patch and Ropinirole placebo tab	Drug: Placebo; SPM962-placebo patch and Ropinirole-placebo tab

Outcome Measures

Primary Outcome Measures

1. Unified Parkinson's Disease Rating Score (UPDRS) Part 3 Sum Score [baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in UPDRS Part 3 sum score (on state) at 16 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.

Secondary Outcome Measures

1. UPDRS Part 3 Sum Score [baseline, 8 and 10 weeks after dosing]

   Mean change (LOCF) from baseline in UPDRS Part 3 sum score (on state) at 8 and 10 weeks after dosing. UPDRS 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.

2. UPDRS Part 2 Sum Score [Baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) at 16 weeks after dosing. UPDRS 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.

3. Off Time [Baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in off time at 16 weeks after dosing. Off-time is a state where L-Dopa becomes ineffective. Off-time was measured by patient diary in hours/day.

4. Parkinson's Disease Sleep Scale-2 (PDSS-2) [Baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in PDSS-2 sum score at 16 weeks after dosing. PDSS-2 is a scale for assessing sleep disorders in Parkinson's disease. PDSS consists of 15 questions about sleep and nocturnal disturbances. The score of each question ranges from 0 (never) to 4 (very frequent). The sum of each question serves as the scale score. Thus a decrease in the scores means improvement.

5. On Time [Baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in on time at 16 weeks after dosing. On-time is a state where L-Dopa is effective. On-time was measured by patient diary in hours/day.

6. On Time Without Dyskinesia Disturbing Daily Activities [Baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in on time without dyskinesia disturbing daily activities at 16 weeks after dosing. On-time is a state where L-Dopa is effective. On-time was measured by patient diary in hours/day.

7. On Time With Dyskinesia Disturbing Daily Activities [Baseline, 16 weeks after dosing]

   Mean change (LOCF) from baseline in on time with dyskinesia disturbing daily activities at 16 weeks after dosing (rate against on time).

8. Effective Rate in UPDRS Part 3 Sum Score [Baseline, 16 weeks after dosing]

   Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 3 sum score (on state) at 16 weeks after dosing.

9. Effective Rate in UPDRS Part 2 Sum Score [Baseline, 16 weeks after dosing]

   Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score (average scores of on state and off state) at 16 weeks after dosing.

10. Effective Rate in Off Time [Baseline, 16 weeks after dosing]

    Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in off time at 16 weeks after dosing. On-time is a state where L-Dopa is effective. On-time was measured by patient diary in hours/day.

11. Clinical Global Impression (CGI) [Baseline, 16 weeks after dosing]

    Change (LOCF) from baseline in CGI score. CGI improvement is a clinician-reported scale for assessing how much the patient's illness has improved or worsened from baseline. The scale scoring criteria are 1: very much improved, 2: much improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: much worse, 7: very much worse. A decrease in the scores means improvement.

12. Dystonia (at an Early Hour) [Baseline, 16 weeks after dosing]

    Change (LOCF) from baseline in occurrence of Dystonia (at an early hour).

13. Dystonia (in the Daytime) [Baseline, 16 weeks after dosing]

    Change (LOCF) from baseline in occurrence of Dystonia (in the daytime).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject diagnosed as having Parkinson's disease in accordance with "Diagnostic Criteria established by the Research Committee of MHLW-specified Intractable Neurodegenerative Diseases (1995)".

• Subject is 30 and more and less than 80 years of age at the time of informed consent.

• Hoehn & Yahr stage 2-4 (on time).

• Total UPDRS Part 3 score is over 10 at screening test (on time).

• Subject is on a stable dose of L-dopa with no change in daily dose or dosing regimen for at least 28 days prior to the initial treatment of SPM 962.

• Subject has any of the following problematic symptoms; 1) Wearing off phenomenon (including frozen gait at off time and dystonia at off time) 2) On and off phenomenon

1. Delayed-on and/or No-on phenomenon 4) Dyskinesia 5) Not well controlled with L-dopa.

Exclusion Criteria:

• Subject who has previously participated in a clinical trial of SPM962 and taken the investigational product (IP).

• Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening test or baseline.

• Subject whose SBP declines by at least 30 mmHg from supine to standing position based on the orthostatic hypotension assessment, or subject who develops orthostatic hypotension at baseline.

• Subject has a history of epilepsy, convulsion and other.

• Subject who has complications or a history of serious cardiac diseases or arrhythmia (eg, congestive heart failure of class 3 or 4 in the NYHA classification, second or third degree atrioventricular block, complete left bundle branch block, sick sinus syndrome, ventricular fibrillation, myocardial infarction within 12 months prior to the screening test, or a complication of angina pectoris).

• Subjects has QTc-interval >450 msec twice at screening. Subject has a the average QTc-interval from two ECGs >450 msec in males and >470 msec in females at baseline.

• Subject has congenital long QT syndrome.

• Subject whose serum potassium level is < 3.5mEq/L at the screening test.

• 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 screening test, or suffers complications of active phase of chronic hepatitis or liver cirrhosis.

• Subject has BUN >= 30 mg/dL or serum creatinine >= 2.0 mg/dl at screening test.

• Subject has a history of allergic reaction to topical agents such as transdermal patch.

• Subject has a history of known intolerance/hypersensitivity to ropinirole and/or adverse drug reactions that prevent subject from receiving treatment.

• Subject is pregnant or nursing or woman who plans pregnancy during the trial.

• Subject is receiving therapy with prohibited drug specified in the study protocol.

• Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal tissue transplant.

• Subject has dementia, including DLB and PDD (MMSE score <= 24 at screening).

• Subject who has a complication or history of malignant neoplastic disease, or received treatment for the disease within 12 months prior to the screening test.

• Subject is unable to give consent.

• Subject who is unable to properly record information in a diary.

• Subject is participating in another trial of IPs or received other IPs within 12 weeks prior to commencement of study treatment.

• Investigator judges that subject is inappropriate as a study subject with other reasons.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chubu Region		Japan
2		Chugoku Region		Japan
3		Hokkaido Region		Japan
4		Kanto Region		Japan
5		Kinki Region		Japan
6		Kyushu Region		Japan
7		Shikoku Region		Japan
8		Tohoku Region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Kyoji Imaoka, Mr, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01628926
• Other Study ID Numbers: 243-08-001; JapicCTI-090888
• First Posted: Jun 27, 2012
• Last Update Posted: May 23, 2014
• Last Verified: Apr 1, 2014

• Additional relevant MeSH terms: Parkinson Disease; Ropinirole

Study Results

Participant Flow

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch	Ropinirole tablet	SPM962 placebo patch and Ropinirole placebo tab
Period Title: Overall Study
STARTED	168	167	85
COMPLETED	142	144	68
NOT COMPLETED	26	23	17

Baseline Characteristics

Arm/Group Title	SPM 962	Ropinirole	Placebo	Total
Arm/Group Description	SPM 962 transdermal patch	Ropinirole tablet	SPM962 placebo patch and Ropinirole placebo tab	Total of all reporting groups
Overall Participants	164	166	84	414
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	71 43.3%	52 31.3%	28 33.3%	151 36.5%
>=65 years	93 56.7%	114 68.7%	56 66.7%	263 63.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (8.8)	67.0 (7.9)	65.3 (7.9)	65.8 (8.3)
Sex: Female, Male (Count of Participants)
Female	103 62.8%	98 59%	42 50%	243 58.7%
Male	61 37.2%	68 41%	42 50%	171 41.3%
Region of Enrollment (participants) [Number]
Japan	164 100%	166 100%	84 100%	414 100%

Outcome Measures

1. Primary Outcome

Title	Unified Parkinson's Disease Rating Score (UPDRS) Part 3 Sum Score
Description	Mean change (LOCF) from baseline in UPDRS Part 3 sum score (on state) at 16 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, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS), last observation carried forward (LOCF)

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	164	166	84
Mean (Standard Deviation) [Scores on a scale]	-10.9 (8.1)	-9.5 (8.7)	-4.5 (9.7)

2. Secondary Outcome

Title	UPDRS Part 3 Sum Score
Description	Mean change (LOCF) from baseline in UPDRS Part 3 sum score (on state) at 8 and 10 weeks after dosing. UPDRS 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, 8 and 10 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	164	166	84
8 weeks after dosing	-9.7 (7.2)	-8.4 (8.1)	-5.5 (8.3)
10 weeks after dosing	-9.9 (7.1)	-8.8 (8.3)	-5.3 (9.0)

3. Secondary Outcome

Title	UPDRS Part 2 Sum Score
Description	Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) at 16 weeks after dosing. UPDRS 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, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	163	166	84
Mean (Standard Deviation) [Scores on a scale]	-3.6 (4.1)	-2.9 (3.5)	-1.3 (3.4)

4. Secondary Outcome

Title	Off Time
Description	Mean change (LOCF) from baseline in off time at 16 weeks after dosing. Off-time is a state where L-Dopa becomes ineffective. Off-time was measured by patient diary in hours/day.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS subjects with measurable off time data at baseline, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	111	113	57
Mean (Standard Deviation) [Hours/day]	-1.3 (2.9)	-2.0 (3.0)	-0.4 (2.7)

5. Secondary Outcome

Title	Parkinson's Disease Sleep Scale-2 (PDSS-2)
Description	Mean change (LOCF) from baseline in PDSS-2 sum score at 16 weeks after dosing. PDSS-2 is a scale for assessing sleep disorders in Parkinson's disease. PDSS consists of 15 questions about sleep and nocturnal disturbances. The score of each question ranges from 0 (never) to 4 (very frequent). The sum of each question serves as the scale score. Thus a decrease in the scores means improvement.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	162	165	81
Mean (Standard Deviation) [Scores on a scale]	-3.1 (6.8)	-3.4 (7.6)	-1.8 (7.0)

6. Secondary Outcome

Title	On Time
Description	Mean change (LOCF) from baseline in on time at 16 weeks after dosing. On-time is a state where L-Dopa is effective. On-time was measured by patient diary in hours/day.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	164	165	83
Mean (Standard Deviation) [Hours/day]	1.3 (2.7)	1.7 (2.9)	0.2 (2.6)

7. Secondary Outcome

Title	On Time Without Dyskinesia Disturbing Daily Activities
Description	Mean change (LOCF) from baseline in on time without dyskinesia disturbing daily activities at 16 weeks after dosing. On-time is a state where L-Dopa is effective. On-time was measured by patient diary in hours/day.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF Evaluation for this outcome measure was not possible, because only 22.6% (37/164), 12.7% (21/165), and 6.0% (5/83) of the subjects in the SPM 962, Ropinirole, and Placebo groups, respectively, had dyskinesia disturbing daily activities on either day from baseline until the end of titration/maintenance.

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	164	165	83
Mean (Standard Deviation) [Hours/day]	1.1 (2.9)	1.6 (3.0)	0.3 (2.6)

8. Secondary Outcome

Title	On Time With Dyskinesia Disturbing Daily Activities
Description	Mean change (LOCF) from baseline in on time with dyskinesia disturbing daily activities at 16 weeks after dosing (rate against on time).
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF Evaluation for this outcome measure was not possible, because only 22.6% (37/164), 12.7% (21/165), and 6.0% (5/83) of the subjects in the SPM 962, Ropinirole, and Placebo groups, respectively, had dyskinesia disturbing daily activities on either day from baseline until the end of titration/maintenance period.

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab.
Measure Participants	37	21	5
Mean (Standard Deviation) [Hours]	1.3 (11.0)	0.6 (7.8)	-0.2 (1.4)

9. Secondary Outcome

Title	Effective Rate in UPDRS Part 3 Sum Score
Description	Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 3 sum score (on state) at 16 weeks after dosing.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	164	166	84
≥20% decrease	80.5 49.1%	69.1 41.6%	56.6 67.4%
≥30% decrease	69.5 42.4%	60.6 36.5%	39.8 47.4%

10. Secondary Outcome

Title	Effective Rate in UPDRS Part 2 Sum Score
Description	Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score (average scores of on state and off state) at 16 weeks after dosing.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	163	166	84
≥20% decrease	65.2 39.8%	56.7 34.2%	47.0 56%
≥30% decrease	55.9 34.1%	43.3 26.1%	28.9 34.4%

11. Secondary Outcome

Title	Effective Rate in Off Time
Description	Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in off time at 16 weeks after dosing. On-time is a state where L-Dopa is effective. On-time was measured by patient diary in hours/day.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS subjects with measurable off time data at baseline, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	111	113	57
≥20% decrease	61.8 37.7%	65.5 39.5%	47.4 56.4%
≥30% decrease	55.5 33.8%	61.9 37.3%	40.4 48.1%

12. Secondary Outcome

Title	Clinical Global Impression (CGI)
Description	Change (LOCF) from baseline in CGI score. CGI improvement is a clinician-reported scale for assessing how much the patient's illness has improved or worsened from baseline. The scale scoring criteria are 1: very much improved, 2: much improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: much worse, 7: very much worse. A decrease in the scores means improvement.
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	163	165	81
Decreased	50.3 30.7%	49.1 29.6%	30.9 36.8%
Decreased (by at least 2 points)	8.0 4.9%	8.5 5.1%	3.7 4.4%
Increased	3.1 1.9%	4.2 2.5%	4.9 5.8%
Increased (by at least 2 points)	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Dystonia (at an Early Hour)
Description	Change (LOCF) from baseline in occurrence of Dystonia (at an early hour).
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

FAS, LOCF Evaluation for this outcome measure was not possible, because 87.1% (142/163), 88.5% (146/165), and 91.4% (74/81) of the subjects in the SPM 962, Ropinirole, and Placebo groups, respectively, had no dystonia in the day time at baseline.

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab.
Measure Participants	163	165	81
Decreased	10.4 6.3%	10.9 6.6%	7.4 8.8%
Decreased (by at least 2 events)	1.8 1.1%	4.2 2.5%	2.5 3%
Increased	1.2 0.7%	3.0 1.8%	3.7 4.4%
Increased (by at least 2 events)	0 0%	0.6 0.4%	0 0%

14. Secondary Outcome

Title	Dystonia (in the Daytime)
Description	Change (LOCF) from baseline in occurrence of Dystonia (in the daytime).
Time Frame	Baseline, 16 weeks after dosing

Outcome Measure Data

Analysis Population Description

Appropriate interpretation for this outcome measure was not possible, because 87.1% (142/163), 88.5% (146/165), and 91.4% (74/81) of the subjects in the SPM 962, Ropinirole, and Placebo groups, respectively, had no dystonia in the day time at baseline.

Arm/Group Title	SPM 962	Ropinirole	Placebo
Arm/Group Description	SPM 962 transdermal patch once a daily up to 36.0 mg/day	Ropinirole oral administration TID up to 15.0 mg/day	SPM962-placebo patch and Ropinirole-placebo tab
Measure Participants	163	165	81
Decreased	8.6 5.2%	7.9 4.8%	3.7 4.4%
Decreased (by at least 2 events)	3.7 2.3%	5.5 3.3%	2.5 3%
Increased	3.7 2.3%	2.4 1.4%	4.9 5.8%
Increased (by at least 2 events)	1.8 1.1%	0.6 0.4%	1.2 1.4%

Adverse Events

Time Frame	21 weeks
Arm/Group Title	SPM 962		Ropinirole		Placebo
Arm/Group Description	SPM 962 transdermal patch		Ropinirole tablet		SPM962 placebo patch and Ropinirole placebo tab
All Cause Mortality
	SPM 962		Ropinirole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SPM 962		Ropinirole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/168 (4.2%)		5/167 (3%)		6/85 (7.1%)
Cardiac disorders
Angina Pectoris	0/168 (0%)	0	0/167 (0%)	0	1/85 (1.2%)	1
Gastrointestinal disorders
Gastric Ulcer	1/168 (0.6%)	1	0/167 (0%)	0	0/85 (0%)	0
Gastric Ulcer Bleeding	0/168 (0%)	0	1/167 (0.6%)	1	0/85 (0%)	0
Ileus	1/168 (0.6%)	1	0/167 (0%)	0	0/85 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/168 (0%)	0	1/167 (0.6%)	1	0/85 (0%)	0
Cholelithiasis	0/168 (0%)	0	1/167 (0.6%)	1	0/85 (0%)	0
Infections and infestations
Pneumonia	0/168 (0%)	0	0/167 (0%)	0	1/85 (1.2%)	1
Urinary Tract Infection	0/168 (0%)	0	0/167 (0%)	0	1/85 (1.2%)	1
Injury, poisoning and procedural complications
Spinal Compression Fracture	1/168 (0.6%)	1	0/167 (0%)	0	1/85 (1.2%)	1
Femoral Neck Fracture	1/168 (0.6%)	1	0/167 (0%)	0	0/85 (0%)	0
Musculoskeletal and connective tissue disorders
Torticollis	1/168 (0.6%)	1	0/167 (0%)	0	0/85 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoma Gastric	0/168 (0%)	0	0/167 (0%)	0	1/85 (1.2%)	1
Breast Cancer	0/168 (0%)	0	1/167 (0.6%)	1	0/85 (0%)	0
Nervous system disorders
Posture Abnormal	1/168 (0.6%)	1	0/167 (0%)	0	0/85 (0%)	0
Disease Parkinson's	1/168 (0.6%)	1	1/167 (0.6%)	1	1/85 (1.2%)	1
Cerebral Artery Embolism	0/168 (0%)	0	0/167 (0%)	0	1/85 (1.2%)	1
Psychiatric disorders
Delusion	0/168 (0%)	0	1/167 (0.6%)	1	0/85 (0%)	0
Renal and urinary disorders
Caruncle Urethral	1/168 (0.6%)	1	0/167 (0%)	0	0/85 (0%)	0
Respiratory, thoracic and mediastinal disorders
Embolism Pulmonary	0/168 (0%)	0	0/167 (0%)	0	1/85 (1.2%)	1
Other (Not Including Serious) Adverse Events
	SPM 962		Ropinirole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/168 (83.3%)		99/167 (59.3%)		40/85 (47.1%)
Gastrointestinal disorders
Nausea	25/168 (14.9%)	27	23/167 (13.8%)	26	7/85 (8.2%)	8
Vomiting	11/168 (6.5%)	15	11/167 (6.6%)	13	2/85 (2.4%)	2
General disorders
Application Site Reaction	91/168 (54.2%)	93	30/167 (18%)	33	10/85 (11.8%)	11
Application Site Pruritus	6/168 (3.6%)	7	0/167 (0%)	0	0/85 (0%)	0
Oedema Peripheral	0/168 (0%)	0	2/167 (1.2%)	2	3/85 (3.5%)	3
Infections and infestations
Nasopharyngitis	28/168 (16.7%)	38	24/167 (14.4%)	29	13/85 (15.3%)	17
Cystitis	3/168 (1.8%)	3	3/167 (1.8%)	3	4/85 (4.7%)	5
Injury, poisoning and procedural complications
Contusion	7/168 (4.2%)	7	2/167 (1.2%)	2	6/85 (7.1%)	8
Investigations
Blood Creatine Phosphokinase Increased	5/168 (3%)	5	6/167 (3.6%)	6	1/85 (1.2%)	2
Musculoskeletal and connective tissue disorders
Back Pain	3/168 (1.8%)	3	5/167 (3%)	5	2/85 (2.4%)	2
Nervous system disorders
Dyskinesia	27/168 (16.1%)	28	23/167 (13.8%)	23	1/85 (1.2%)	1
Psychiatric disorders
Hallucination Visual	13/168 (7.7%)	14	10/167 (6%)	10	3/85 (3.5%)	3
Somnolence	11/168 (6.5%)	11	9/167 (5.4%)	9	2/85 (2.4%)	2
Hallucination	3/168 (1.8%)	3	6/167 (3.6%)	6	0/85 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Inflammation	3/168 (1.8%)	4	1/167 (0.6%)	1	3/85 (3.5%)	4
Vascular disorders
Orthostatic Hypotension	5/168 (3%)	5	7/167 (4.2%)	8	4/85 (4.7%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.