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

• ClinicalTrials.gov Identifier: NCT01562743
• Recruitment Status: Completed
• First Posted: March 26, 2012
• Results First Posted: April 23, 2014
• Last Update Posted: April 23, 2014
• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: March 22, 2012
• First Posted Date: March 26, 2012
• Results First Submitted Date: February 3, 2014
• Results First Posted Date: April 23, 2014
• Last Update Posted Date: April 23, 2014
• Study Start Date: August 2008
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2014)

• The Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters [ Time Frame: Up to 54 weeks ]
  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
• Augmentation [ Time Frame: Up to 53 weeks ]
  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).
• Change of the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Each Visit [ Time Frame: Baseline, Up to 53 weeks ]
  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.

Original Primary Outcome Measures (submitted: March 22, 2012)

the incidence and severity of adverse events, vital signs, and laboratory parameters [ Time Frame: Up to 53 weeks ]

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.

Current Secondary Outcome Measures (submitted: March 26, 2014)

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

• Original Secondary Outcome Measures (submitted: March 22, 2012): Change of IRLS sum score from the baseline to each visit [ Time Frame: Up to 53 weeks ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Long-Term Extension Trial From Late Phase II of SPM 962 in Patients With Restless Legs Syndrome
• Official Title: An Open-label Long-term Extension Trial From Late Phase II of SPM 962 (243-07-003) in Patients With Restless Legs Syndrome
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Idiopathic Restless Legs Syndrome

Intervention

Drug: SPM 962

Tansdermal patch

Other Name: rotigotine

Study Arms

Experimental: SPM 962

Rotigotine transdermal patch

Intervention: Drug: SPM 962

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 22, 2012): 185
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT01562743
• Other Study ID Numbers: 243-07-004
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• Study Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Otsuka Pharmaceutical Co., Ltd.
• Verification Date: March 2014