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Study of SPM 962 in Patients With Restless Legs Syndrome (RLS)

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ClinicalTrials.gov Identifier: NCT01084551
Recruitment Status : Completed
First Posted : March 10, 2010
Results First Posted : June 5, 2014
Last Update Posted : June 5, 2014
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Idiopathic Restless Legs Syndrome
Interventions Drug: SPM 962
Drug: Placebo of SPM 962
Enrollment 284
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description 0 mg/day for 13 weeks started at 2.25 mg/day to 4.5 mg/day for 13 weeks started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Period Title: Overall Study
Started 95 95 94
Completed 86 81 86
Not Completed 9 14 8
Reason Not Completed
Adverse Event             2             9             4
Lack of Efficacy             2             0             1
Withdrawal by Subject             2             1             0
Protocol Violation             2             4             0
Lost to Follow-up             0             0             3
Physician Decision             1             0             0
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75 Total
Hide Arm/Group Description 0 mg/day for 13 weeks started at 2.25 mg/day to 4.5 mg/day for 13 weeks started at 2.25 mg/day to 6.75 mg/day for 13 weeks Total of all reporting groups
Overall Number of Baseline Participants 95 95 94 284
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 95 participants 95 participants 94 participants 284 participants
53.4  (15.3) 50.7  (13.3) 50.9  (13.7) 51.7  (14.1)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 95 participants 94 participants 284 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
65
  68.4%
77
  81.1%
77
  81.9%
219
  77.1%
>=65 years
30
  31.6%
18
  18.9%
17
  18.1%
65
  22.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 95 participants 94 participants 284 participants
Female
54
  56.8%
54
  56.8%
46
  48.9%
154
  54.2%
Male
41
  43.2%
41
  43.2%
48
  51.1%
130
  45.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 95 participants 95 participants 94 participants 284 participants
95 95 94 284
1.Primary Outcome
Title International Restless Legs Syndrome Rating Scale (IRLS) Total Score
Hide Description

Change from the baseline to the end of dose-titration/dose-maintenance period. IRLS is a scale for assessing severity of restless legs syndrome symptoms. IRLS consists of ten questions. Each question is scored from 4 for the first (top) answer (usually ‘very severe’) to 0 for the last answer (usually none).

The sum of the score of each question serves as the scale score. The scale scoring criteria are: Mild (score 1-10); Moderate (score 11-20); Severe (score 21-30); Very severe (score 31-40). A decrease in the scores means improvement.

Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS), last observation carried forward (LOCF)
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 94
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-11.6  (8.2) -14.3  (8.9) -14.6  (9.0)
2.Secondary Outcome
Title Clinical Global Impression (CGI) Improvement
Hide Description

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.

Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 93
Measure Type: Number
Unit of Measure: Percentage of Participants
Subjects with “much improved” 24.2 25.8 29.0
Subjects with “very much improved” 33.7 41.9 45.2
3.Secondary Outcome
Title Patient Global Impression (PGI) Improvement
Hide Description

PGI improvement is a patient-reported scale for assessing how much the patient's illness has improved or worsened from baseline.

The scale scoring criteria are 1: very much better, 2: much better, 3: a little better, 4: no change, 5: a little worse, 6: much worse, 7: very much worse.

Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 93
Measure Type: Number
Unit of Measure: Percentage of Participants
Subjects with “much improved” 23.2 24.7 30.1
Subjects with “very much improved” 38.9 48.4 50.5
4.Secondary Outcome
Title The Pittsburgh Sleep Quality Index (PSQI)
Hide Description

Change of PSQI from baseline to the end of dose-titration/dose-maintenance period.

PSQI is a scale for assessing severity of sleep disorders. The score ranges from 0 to 21. 0 indicates “no difficulty” and 21 indicates “severe difficulty”. A decrease in the scores means improvement.

Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 94 93 90
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-2.5  (2.4) -3.1  (3.2) -3.2  (3.3)
5.Secondary Outcome
Title Each Item of IRLS (10 Items)
Hide Description

IRLS is a scale for assessing severity of restless legs syndrome symptoms. IRLS consists of ten questions. Each question is scored from 4 for the first (top) answer (usually 'very severe') to 0 for the last answer (usually none).

Numbers of subjects with -4 or -3 score change from baseline in each item of IRLS. A decrease in the scores means improvement.

Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 94
Measure Type: Number
Unit of Measure: percentage of participants
-4 (RLS discomfort) 1.1 2.2 6.4
-3 (RLS discomfort) 11.6 17.2 12.8
-4 (need to move around due to RLS symptoms) 2.1 2.2 7.4
-3 (need to move around due to RLS symptoms) 11.6 25.8 18.1
-4 (discomfort relief by moving around) 0 1.1 2.1
-3 (discomfort relief by moving around) 10.5 20.4 28.7
-4 (severity of RLS as a whole) 1.1 1.1 4.3
-3 (severity of RLS as a whole) 6.3 12.9 12.8
-4 (RLS symptoms frequency) 12.6 24.7 26.6
-3 (RLS symptoms frequency) 12.6 9.7 11.7
-4 (average duration of RLS symptoms) 1.1 2.2 2.1
-3 (average duration of RLS symptoms) 6.3 10.8 9.6
-4 (severity of sleep disturbance) 2.1 4.3 6.4
-3 (severity of sleep disturbance) 16.8 16.1 21.3
-4 (tiredness or sleepiness during the day) 0 2.2 2.1
-3 (tiredness or sleepiness during the day) 8.4 11.8 8.5
-4 (severity of the impact on daily affairs) 0 1.1 1.1
-3 (severity of the impact on daily affairs) 8.4 11.8 4.3
-4 (severity of mood disturbance) 1.1 4.3 1.1
-3 (severity of mood disturbance) 8.4 10.8 12.8
6.Secondary Outcome
Title Incidence of RLS Symptoms
Hide Description Incidence rate of RLS symptoms is calculated as the number of days with RLS symptoms in the week / the number of evaluation days in the week* 100%
Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 92
Mean (Standard Deviation)
Unit of Measure: percentage of days with RLS symptom
Baseline 85.7  (20.8) 85.4  (20.5) 83.2  (22.2)
Week 13 48.7  (40.9) 35.8  (38.6) 36.8  (38.8)
7.Secondary Outcome
Title Average Duration of RLS Symptoms
Hide Description Change of average duration of RLS symptoms in a week from baseline to the end of dose-titration/dose-maintenance period. Only the days with RLS symptoms are used for calculation.
Time Frame Baseline, the end of dose-titration/dose-maintenance period (weeks 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 71 59 55
Mean (Standard Deviation)
Unit of Measure: Hours
-3.1  (4.7) -3.7  (4.6) -4.3  (4.4)
8.Secondary Outcome
Title Incidence of RLS Symptoms in the Evening and Night
Hide Description Incidence rate of RLS symptoms is calculated as the number of days with RLS symptoms / the number of days of evaluation * 100%.
Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 92
Mean (Standard Deviation)
Unit of Measure: percentage of days/week with symptoms
Baseline 80.6  (24.2) 83.3  (20.8) 79.5  (24.2)
Week 13 45.4  (41.0) 34.6  (38.2) 31.8  (37.7)
9.Secondary Outcome
Title Average Duration of RLS Symptoms in the Evening and Night in a Week
Hide Description Change of average duration of RLS symptoms in a week from baseline to the end of dose-titration/dose-maintenance period. Only the days with RLS symptoms are used for calculation.
Time Frame Baseline, the end of dose-titration/dose-maintenance period (weeks 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 69 58 50
Mean (Standard Deviation)
Unit of Measure: Hours
-1.3  (3.1) -1.8  (2.5) -1.5  (2.3)
10.Secondary Outcome
Title Nocturnal Awakenings Due to RLS Symptoms in a Week
Hide Description Nocturnal awakening rate is calculated as the number of days with nocturnal awakenings / the number of days of evaluation * 100%.
Time Frame Baseline, the end of dose-titration/dose-maintenance period (week 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 92
Mean (Standard Deviation)
Unit of Measure: percentage of days/week with awakening
Baseline 33.5  (35.9) 22.6  (31.3) 28.3  (34.3)
Week 13 15.6  (31.7) 7.7  (20.5) 7.5  (19.5)
11.Secondary Outcome
Title Average Sleep Time in a Week
Hide Description Change of average sleep time in a week from baseline to the end of dose-titration/dose-maintenance period.
Time Frame Baseline, the end of dose-titration/dose-maintenance period (weeks 13)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS, LOCF
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description:
Once a daily transdermal administration for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 4.5 mg/day for 13 weeks
Once a daily transdermal administration of SPM 962 started at 2.25 mg/day to 6.75 mg/day for 13 weeks
Overall Number of Participants Analyzed 95 93 92
Mean (Standard Deviation)
Unit of Measure: Hours
0.4  (0.8) 0.5  (1.1) 0.4  (1.1)
Time Frame 14 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo SPM 962 4.5 SPM 962 6.75
Hide Arm/Group Description 0 mg/day for 13 weeks started at 2.25 mg/day to 4.5 mg/day for 13 weeks started at 2.25 mg/day to 6.75 mg/day for 13 weeks
All-Cause Mortality
Placebo SPM 962 4.5 SPM 962 6.75
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo SPM 962 4.5 SPM 962 6.75
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/95 (2.11%)      0/95 (0.00%)      1/94 (1.06%)    
Injury, poisoning and procedural complications       
Contusion * 1  0/95 (0.00%)  0 0/95 (0.00%)  0 1/94 (1.06%)  1
Traffic Accident * 1  0/95 (0.00%)  0 0/95 (0.00%)  0 1/94 (1.06%)  1
Nervous system disorders       
Lacunar Infarction * 1  1/95 (1.05%)  1 0/95 (0.00%)  0 0/94 (0.00%)  0
VIIth Nerve Paralysis * 1  1/95 (1.05%)  1 0/95 (0.00%)  0 0/94 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA(13.1)J
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo SPM 962 4.5 SPM 962 6.75
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/95 (33.68%)      72/95 (75.79%)      77/94 (81.91%)    
Cardiac disorders       
Ventricular Extrasystoles * 1  0/95 (0.00%)  0 0/95 (0.00%)  0 3/94 (3.19%)  3
Gastrointestinal disorders       
Nausea * 1  9/95 (9.47%)  12 32/95 (33.68%)  37 41/94 (43.62%)  48
Vomiting * 1  1/95 (1.05%)  2 4/95 (4.21%)  5 10/94 (10.64%)  11
Abdominal Discomfort * 1  3/95 (3.16%)  3 0/95 (0.00%)  0 10/94 (10.64%)  11
Abdominal Pain * 1  0/95 (0.00%)  0 3/95 (3.16%)  3 1/94 (1.06%)  1
Constipation * 1  0/95 (0.00%)  0 3/95 (3.16%)  3 3/94 (3.19%)  3
Diarrhoea * 1  3/95 (3.16%)  3 0/95 (0.00%)  0 1/94 (1.06%)  1
General disorders       
Application Site Reaction * 1  7/95 (7.37%)  8 40/95 (42.11%)  41 47/94 (50.00%)  50
Malaise * 1  1/95 (1.05%)  2 2/95 (2.11%)  2 3/94 (3.19%)  3
Infections and infestations       
Nasopharyngitis * 1  12/95 (12.63%)  17 12/95 (12.63%)  14 16/94 (17.02%)  17
Nervous system disorders       
Headache * 1  0/95 (0.00%)  0 5/95 (5.26%)  6 2/94 (2.13%)  2
Dizziness * 1  3/95 (3.16%)  3 2/95 (2.11%)  2 1/94 (1.06%)  1
Psychiatric disorders       
Somnolence * 1  2/95 (2.11%)  2 10/95 (10.53%)  10 14/94 (14.89%)  14
Respiratory, thoracic and mediastinal disorders       
Upper Respiratory Tract Inflammation * 1  1/95 (1.05%)  1 3/95 (3.16%)  4 4/94 (4.26%)  4
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA(13.1)J
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.
Results Point of Contact
Name/Title: Director of Clinical Research and Development
Organization: Otsuka Pharmaceutical Co., Ltd.
Phone: +81-3-6361-7366
Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT01084551     History of Changes
Other Study ID Numbers: 243-09-001
JapicCTI-101053
First Submitted: March 4, 2010
First Posted: March 10, 2010
Results First Submitted: February 3, 2014
Results First Posted: June 5, 2014
Last Update Posted: June 5, 2014