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

An Open-label Long-term Extension Trial From Late Phase II of SPM 962 (243-07-003) in Patients With Restless Legs Syndrome

The aims of the trial are to assess the safety and the efficacy of SPM 962 following once-a-daily transdermal administration within a range of 2.25 to 6.75 mg/day in Japanese patients with restless legs syndrome (RLS) in a multi-center, open-label trial. The maximum treatment period is 53 weeks. The trial is an extension trial from the precedent 6-week, double-blind, randomized, placebo-controlled, parallel-group comparative trial(243-07-003). The trial is also for an exploratory investigation of incidence of augmentation, the most problematic complications in dopaminergic treatment.

Study Overview

• Status: Completed
• Conditions: Idiopathic Restless Legs Syndrome
• Intervention / Treatment: Drug: SPM 962

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject completed the preceding trial 243-07-003 (NCT00666965)

Exclusion Criteria:

• Subject discontinued from the preceding trial 243-07-003 (NCT00666965)
• Subject had a serious adverse event which association with the investigational drug is not ruled out during trial 243-07-003
• Subject had a persistent serious adverse event at the baseline, which was observed and association with the investigational drug is ruled out during trial 243-07-003.
• Subject had persistent hallucination or delusion during trial 243-07-003.
• Subject had psychiatric conditions such as confusion, excitation, delirium, abnormal behaviour at the baseline.
• Subject had orthostatic hypotension or a systolic blood pressure (SBP) ≤ 100 mmHg and had a decrease of SBP from spine to standing position ≥ 30 mmHg at baseline.
• Subject had a history of epilepsy, convulsion etc. during trial 243-07-003.
• Subject developed serious ECG abnormality at the baseline.
• Subject had QTc-interval ≥ 500 msec at the baseline or subject had an increase of QTc-interval ≥ 60 msec from the baseline in the trial 243-07-003 and had 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 243-07-003.
• Subject had 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 243-07-003.
• Subject had BUN ≥ 30 mg/dL or serum creatinine ≥ 2.0 mg/dl at the end of the taper period in trial 243-07-003.
• Subject who planned pregnancy during the trial.
• Subject was judged to be inappropriate for this trial by the investigator for the reasons other than above.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPM 962; Rotigotine transdermal patch	Drug: SPM 962; Tansdermal patch; Other Names: rotigotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 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 adverse events, vital signs, and laboratory parameters. AEs of special interest (1-3) are defined as below: sudden onset of sleep; obsessive-compulsive disorder or impulse-control disorder; hallucination, delusion	Up to 54 weeks
Augmentation	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: Change in daily activities and/or behavior (e.g., the patient stops riding in cars in the afternoon) due to augmentation;; Negative impact on the patient's quality of life (sleep, mood, etc.) due to augmentation;; Need to change the treatment dose or the patienｔ needs to take the dose earlier in the day (e.g., dividing the dose);; 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);; Any other aspect as judged by the evaluator (should be specified).	Up to 53 weeks
Change of the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Each Visit	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.	Baseline, Up to 53 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of IRLS Sum Score From the Baseline to Each Visit	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.	Baseline, Up to 53 weeks
Efficacy Rate in IRLS Sum Score	Efficacy rate (percentage of subjects with 50% decrease) (LOCF) in IRLS sum score.	Baseline, Up to 53 weeks
Change of Augmentation Severity Rating Scale (ASRS) Sum Score From Baseline to Each Visit	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.	Baseline, Up to 52 weeks
Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit	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.	Baseline, Up to 53 weeks

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Inoue Y, Hirata K, Hayashida K, Hattori N, Tomida T, Garcia-Borreguero D; Rotigotine Study Group. Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10;40:326-33. doi: 10.1016/j.pnpbp.2012.10.012. Epub 2012 Oct 25.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: March 22, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 26, 2012

Study Record Updates

• Last Update Posted (Estimate): April 23, 2014
• Last Update Submitted That Met QC Criteria: March 26, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Rotigotine
• Other Study ID Numbers: 243-07-004