Trial Outcomes & Findings for A Long-Term Extension Trial From Late Phase II of SPM 962 in Patients With Restless Legs Syndrome (NCT NCT01562743)

NCT ID: NCT01562743

Last Updated: 2014-04-23

Results Overview

The safety of the long-term SPM 962 treatment was examined based on the incidence and severity of adverse events, 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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 185 participants
• Primary outcome timeframe: Up to 54 weeks
• Results posted on: 2014-04-23

Participant Flow

Participant milestones

Measure	SPM 962 Rotigotine transdermal patch A patch containing 2.25 - 6.75mg of rotigotine was administered once a day.
Overall Study STARTED	185
Overall Study COMPLETED	133
Overall Study NOT COMPLETED	52

Reasons for withdrawal

Measure	SPM 962 Rotigotine transdermal patch A patch containing 2.25 - 6.75mg of rotigotine was administered once a day.
Overall Study Adverse Event	29
Overall Study Lack of Efficacy	3
Overall Study Withdrawal by Subject	13
Overall Study Protocol Violation	1
Overall Study Discontinuation criteria	2
Overall Study Lost to Follow-up	2
Overall Study Physician Decision	2

Baseline Characteristics

A Long-Term Extension Trial From Late Phase II of SPM 962 in Patients With Restless Legs Syndrome

Baseline characteristics by cohort

Measure	SPM 962 n=185 Participants Rotigotine transdermal patch
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	157 Participants n=5 Participants
Age, Categorical >=65 years	28 Participants n=5 Participants
Age, Continuous	49.8 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants
Region of Enrollment Japan	185 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 54 weeks

Population: Safety set (SS)

The safety of the long-term SPM 962 treatment was examined based on the incidence and severity of adverse events, 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

Outcome measures

Measure	SPM 962 n=185 Participants Rotigotine transdermal patch
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Any AEs	175 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Treatment-related AEs	139 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters SAEs	5 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Treatment-related SAEs	1 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Severe AEs	3 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Discontinuation due to AEs	29 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Death	0 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters AEs of special interest 1	0 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters AEs of special interest 2	0 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters AEs of special interest 3	0 participants
The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters Valvular disease of the heart	0 participants

PRIMARY outcome

Timeframe: Up to 53 weeks

Population: SS

Augmentation is the main complication during long-term dopaminergic treatment of restless legs syndrome (RLS) and reflects an overall increase in RLS severity.

Augmentation is clinically significant when at least one of the following occurs:

1. Change in daily activities and/or behavior (e.g., the patient stops riding in cars in the afternoon) due to augmentation;

2. Negative impact on the patient's quality of life (sleep, mood, etc.) due to augmentation;

3. Need to change the treatment dose or the patienｔ needs to take the dose earlier in the day (e.g., dividing the dose);

4. Adjustments in concomitant medication are made to compensate for augmented RLS symptoms (e.g., an increased intake of analgesics or hypnotics to cover an increase in symptom intensity);

5. Any other aspect as judged by the evaluator (should be specified).

Outcome measures

Measure	SPM 962 n=185 Participants Rotigotine transdermal patch
Augmentation Subjects with augmentation	11 participants
Augmentation Subjects with clinically significant augmentation	5 participants

PRIMARY outcome

Timeframe: Baseline, Up to 53 weeks

Population: FAS, LOCF

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.

Outcome measures

Measure	SPM 962 n=182 Participants Rotigotine transdermal patch
Change of the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Each Visit Week 8	-2.2 Scores on a scale Standard Deviation 3.3
Change of the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Each Visit Week 16	-2.2 Scores on a scale Standard Deviation 2.9
Change of the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Each Visit Week 44	-2.0 Scores on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: Baseline, Up to 53 weeks

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

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.

Outcome measures

Measure	SPM 962 n=184 Participants Rotigotine transdermal patch
Change of IRLS Sum Score From the Baseline to Each Visit Weeks 8	-11.4 Scores on a scale Standard Deviation 8.8
Change of IRLS Sum Score From the Baseline to Each Visit Week 16	-9.7 Scores on a scale Standard Deviation 9.6
Change of IRLS Sum Score From the Baseline to Each Visit Week 32	-9.5 Scores on a scale Standard Deviation 9.1
Change of IRLS Sum Score From the Baseline to Each Visit Week 44	-10.4 Scores on a scale Standard Deviation 9.1

SECONDARY outcome

Timeframe: Baseline, Up to 53 weeks

Population: FAS, LOCF

Efficacy rate (percentage of subjects with 50% decrease) (LOCF) in IRLS sum score.

Outcome measures

Measure	SPM 962 n=184 Participants Rotigotine transdermal patch
Efficacy Rate in IRLS Sum Score Weeks 8	64.1 Percentage of participants Interval 57.2 to 71.1
Efficacy Rate in IRLS Sum Score Week 16	54.9 Percentage of participants Interval 47.7 to 62.1
Efficacy Rate in IRLS Sum Score Week 32	57.6 Percentage of participants Interval 50.5 to 64.7
Efficacy Rate in IRLS Sum Score Week 44	60.3 Percentage of participants Interval 53.3 to 67.4

SECONDARY outcome

Timeframe: Baseline, Up to 52 weeks

Population: FAS, LOCF

ASRS is a scale for assessing severity of augmentation. ASRS consists of 3 items (one item containing 4 sub-items). The sum of the score of each question serves as the scale score (each question score: 0-3, sum score 0-24).

A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.

Outcome measures

Measure	SPM 962 n=184 Participants Rotigotine transdermal patch
Change of Augmentation Severity Rating Scale (ASRS) Sum Score From Baseline to Each Visit Week 32	1.6 Scores on a scale Standard Deviation 2.7
Change of Augmentation Severity Rating Scale (ASRS) Sum Score From Baseline to Each Visit Week 44	1.4 Scores on a scale Standard Deviation 2.6
Change of Augmentation Severity Rating Scale (ASRS) Sum Score From Baseline to Each Visit Week 8	1.4 Scores on a scale Standard Deviation 2.5
Change of Augmentation Severity Rating Scale (ASRS) Sum Score From Baseline to Each Visit Week 16	1.4 Scores on a scale Standard Deviation 2.6

SECONDARY outcome

Timeframe: Baseline, Up to 53 weeks

Population: FAS, LOCF

SF-36 is a scale for assessing health status in clinical practice and research. The scores of 36 questions are summarized into 7 sub-scales. In each sub-scale which range is 0-100, a higher score indicates a better health status. Thus a increase in the scores means improvement.

Outcome measures

Measure	SPM 962 n=182 Participants Rotigotine transdermal patch
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit Physical functioning	-0.2 Scores on a scale Standard Deviation 8.0
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit Role physical	3.7 Scores on a scale Standard Deviation 17.4
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit Bodily pain	5.1 Scores on a scale Standard Deviation 22.3
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit General health	1.8 Scores on a scale Standard Deviation 12.8
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit Vitality	4.9 Scores on a scale Standard Deviation 15.8
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit Social functioning	3.0 Scores on a scale Standard Deviation 16.2
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit Role emotional	5.6 Scores on a scale Standard Deviation 14.5

Adverse Events

SPM 962

Serious events: 5 serious events

Other events: 165 other events

Deaths: 0 deaths

Serious adverse events

Measure	SPM 962 n=185 participants at risk Rotigotine transdermal patch
Eye disorders Cataract	0.54% 1/185 • Number of events 1 • 53 weeks
Gastrointestinal disorders Diverticulitis Intestinal Haemorrhagic	0.54% 1/185 • Number of events 1 • 53 weeks
General disorders Application Site Discolouration	0.54% 1/185 • Number of events 1 • 53 weeks
Injury, poisoning and procedural complications Contusion	0.54% 1/185 • Number of events 1 • 53 weeks
Injury, poisoning and procedural complications Neck Crushing	0.54% 1/185 • Number of events 1 • 53 weeks
Injury, poisoning and procedural complications Nerve Root Injury Lumbar	0.54% 1/185 • Number of events 1 • 53 weeks
Injury, poisoning and procedural complications Traffic Accident	0.54% 1/185 • Number of events 1 • 53 weeks
Vascular disorders Haematoma	0.54% 1/185 • Number of events 1 • 53 weeks

Other adverse events

Measure	SPM 962 n=185 participants at risk Rotigotine transdermal patch
Gastrointestinal disorders Nausea	28.6% 53/185 • Number of events 79 • 53 weeks
Gastrointestinal disorders Vomiting	8.1% 15/185 • Number of events 26 • 53 weeks
Gastrointestinal disorders Diarrhoea	6.5% 12/185 • Number of events 12 • 53 weeks
Gastrointestinal disorders Abdominal Pain Upper	5.4% 10/185 • Number of events 11 • 53 weeks
General disorders Application Site Reaction	45.9% 85/185 • Number of events 94 • 53 weeks
General disorders Application Site Pruritus	6.5% 12/185 • Number of events 13 • 53 weeks
General disorders Application Site Erythema	3.2% 6/185 • Number of events 6 • 53 weeks
Infections and infestations Nasopharyngitis	52.4% 97/185 • Number of events 186 • 53 weeks
Infections and infestations Influenza	3.2% 6/185 • Number of events 6 • 53 weeks
Injury, poisoning and procedural complications Fall	5.9% 11/185 • Number of events 11 • 53 weeks
Injury, poisoning and procedural complications Contusion	4.3% 8/185 • Number of events 8 • 53 weeks
Investigations Blood Creatine Phosphokinase Increased	3.2% 6/185 • Number of events 7 • 53 weeks
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 10/185 • Number of events 10 • 53 weeks
Nervous system disorders Headache	13.5% 25/185 • Number of events 34 • 53 weeks
Nervous system disorders Dizziness	4.3% 8/185 • Number of events 12 • 53 weeks
Psychiatric disorders Somnolence	15.7% 29/185 • Number of events 33 • 53 weeks
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Inflammation	4.9% 9/185 • Number of events 11 • 53 weeks
Skin and subcutaneous tissue disorders Eczema	4.9% 9/185 • Number of events 10 • 53 weeks

Additional Information

Director of Clinical Research and Development

Otsuka Pharmaceutical Co., Ltd.

Phone: +81-6361-7366

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place