Switching From Oral Dopamine Agonists to Rotigotine (SWITCH)
The primary objective is to demonstrate safety and tolerability of switching patients with Restless Legs Syndrome (RLS) from an oral dopamine agonist to rotigotine.
As a secondary objective, the investigators will evaluate control of RLS symptoms on rotigotine compared to the prior oral regimen.
|Restless Legs Syndrome Ekbom Syndrome Willis-Ekbom Disease||Drug: Rotigotine||Phase 4|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Method to Switch From Oral Dopamine Agonists to Rotigotine in Patients With Restless Legs Syndrome|
- Proportion of Patients Completing the Switch and Their Adverse Events [ Time Frame: Participants will be monitored for the duration of the study, approximately 6-10 weeks depending upon scheduling of visits ]
The primary endpoint will be the safety and tolerability of switching from an oral dopamine agonist to rotigotine.
The CGIC scales were developed to assess treatment outcomes in pharmacological studies. The scales are meant completed by the clinician in person after assessment of the subject. They include 4 global scales describing the severity of illness, change in severity from baseline, therapeutic efficacy, and tolerability of treatment.
Clinical Global Impression - Improvement scale (CGI-I) rated as: 1, very much improved since the baseline week; 2, much improved; 3, minimally improved; 4, no change from baseline; 5, minimally worse; 6, much worse; or 7, very much worse since the baseline week. The CGI-I was performed at baseline and at Week 5 to see which participants rated as much or very much improved.
Adverse Events are reported in the Adverse Events module.
- International Restless Legs Scale (IRLS) [ Time Frame: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine) ]
The IRLS will be used to determine the overall efficacy of RLS symptom control on rotigotine.
The IRLS is a well-validated instrument for measuring RLS severity during the past week. It includes 10 questions encompassing intensity and frequency of symptoms, associated sleep problems, and the impact of symptoms on the patients' mood and daily functioning. This scale has been shown to have high internal consistency, inter-examiner reliability, test-retest reliability, and convergent validity.
Minimum score 0, maximum score 40. A decrease in the IRLS score indicates a better outcome.
- RLS-6 Scale [ Time Frame: Average of Baseline titration week (approximately days 1-7 of the study) vs. Average of Final Treatment week (integrating data from days 28-35 after initiating the switch from the oral dopamine agonist to the transdermal rotigotine) ]
The RLS-6 scale will be used to determine the overall efficacy of RLS symptom control on rotigotine, calculated as a mean score for each scale during the final treatment week vs baseline.
The RLS-6 scale are 11-point (0=not present to 10=very severe) metrics for measuring RLS severity. Four questions delineate a severity profile of RLS during different night and daytime periods: at bedtime, during the night, during the day at rest, during daily activities. The final two questions assess satisfaction with sleep and severity of sleepiness during the day. The RLS-6 scales have been validated on a day-to-day basis, with relatively low placebo effect compared to other RLS rating scales.
Minimum score 0, maximum score 60. A decrease in the RLS-6 score indicates a better outcome. The RLS-6 scale was completed each day of the study and averaged for the baseline week (approximately days 1-7 of the study) and the final week (approximately days 21-28 of the maintenance period).
- Preference of Medication Scale (POM) [ Time Frame: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine) ]
The POM will be used to assess patient satisfaction with treatment.
The POM scale is designed to summarize subjects' preference for the study medication compared to prior therapy. It asks a single question: "How does this current medicine compare to the previous RLS medicine(s) you were taking?" The response set is as follows: (1) Much Better, I prefer this medication (indicating preference for rotigotine); (2) Slightly Better; (3) About the Same; (4) Slightly Worse; (5) Much Worse, I much prefer my previous medication (indicating preference for oral dopamine agonist).
- The Patient Global Impression of Change Scale [ Time Frame: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine) ]
The Patient Global Impression of Change scale (PGIC) will be used to assess patient satisfaction with treatment.
The PGIC assesses subjective changes in symptoms during clinical trials. This single-item scale asks participants to rate their symptoms as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." The measure provides a responsive and easily interpretable assessment of participants' evaluations of the importance of their improvement or worsening.
- The Clinician Global Impression of Change Scale [ Time Frame: Study Visit 1 (Day 1) and Study Visit 3 (approximately 35 days after initiating the switch from the oral dopamine agonist to the transdermal rotigotine) ]The Clinician Global Impression of Change scale (CGIC) will be used to assess patient satisfaction with treatment.
|Study Start Date:||August 2014|
|Study Completion Date:||December 2015|
|Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: Oral Dopamine Agonist to Rotigotine
During the study, we will switch patients who are not satisfied with their current oral dopamine agonist to rotigotine. Cross-titration will allow determination of the lowest effective dose of rotigotine. We will use as initial guidance the equivalence determined from the Parkinson's Disease trials, in which 1 mg rotigotine was shown to be approximately equivalent to 1-1.5 mg ropinirole or 0.25 -0.375 mg pramipexole. Tolerability, adverse events, and RLS symptom control will be evaluated. These data will provide clinicians with practical guidance to optimize RLS treatment while minimizing adverse events.
Rotigotine is FDA approved for the treatment of Restless Legs Syndrome at doses of 1 mg/24h, 2 mg/24h, and 3 mg/24h. The prescribed dose of rotigotine may be achieved using single or multiple patches. Subjects will titrate the dose based on discussions with the investigator.
Other Name: Neupro
The study will consist of 3 in-person visits and 4 scheduled telephone appointments over the course of approximately 6 weeks. The first visit will be the screening visit during which eligibility will be confirmed and informed consent obtained. After the first visit, subjects will continue their current oral dopamine agonist for a one-week baseline period during which they will record RLS symptoms daily.
The second visit will be the baseline visit. The IRLS scale, a commonly used measure of RLS symptoms, will be obtained. An individualized schedule for down-titration of oral dopamine agonist and concomitant up-titration of rotigotine will be provided. After the second visit, subjects will begin this cross-titration. This will entail a pre-determined incremental taper of the oral medication and flexible up-titration of rotigotine according to symptoms. During this time, subjects will keep diaries of RLS symptoms and will speak with the investigator over the phone a total of 3 times (visits 2a-2c) to discuss dosing of rotigotine.
After the titration is complete, subjects will enter the maintenance period, which will last 28 days. There will be another phone contact (2d) one week after the titration is complete to adjust the dose of rotigotine as needed. The subject will then continue the chosen dose for the next 3 weeks of the maintenance period. There will be one final phone contact (2e) 1 week prior to the end of the maintenance period to remind subjects to resume RLS symptom diaries during the final week of the maintenance period.
The third and final visit will take place at the end of the maintenance period. RLS symptoms will be discussed and the IRLS scale, Clinician Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), and Preference of Medication Scale (POMS) will be administered.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01976871
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|