Assess Efficacy and Safety of the Dopamine Agonist Pramipexole Versus Levodopa / Benserazide (Madopar® DR) in Patients With Restless Legs Syndrome

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to determine that pramipexole (Sifrol) 0.25 mg to 0.75 mg daily is not inferior to levodopa 100 mg to 300 mg (in combination with benserazide 25mg to 75mg = Madopar DR) daily in the treatment of patients with idiopathic restless legs syndrome fulfilling the International Diagnostic Criteria. The efficacy parameters include an objective measure of the leg movements during the time spent in bed, and a quantitative clinical assessment of the severity of RLS, in the form of the RLS-score. In addition, the efficacy evaluations aim at comparing the impact of pramipexole and levodopa on outcome measures such as quality of life and sleep.

Official Title
-----------------
Swiss Restless Legs Syndrome Trial (SRLS) A Double-blind, Randomised, Crossover Trial Investigating the Efficacy and Safety of the Dopamine Agonist Pramipexole (Sifrol®, 0.25-0.75 mg Per Day) Versus Levodopa / Benserazide (Madopar® DR, 125-375 mg Per Day) in Patients With Restless Legs Syndrome

Conditions
-----------------
Restless Legs Syndrome

Intervention / Treatment
-----------------
* Drug: pramipexole
* Drug: levodopa in combination with benserazide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Patients diagnosed with idiopathic restless legs syndrome fulfilling the International Diagnostic Criteria 1 . Male or female patients, aged 25 to 85 years. Patients presenting RLS symptoms almost every day, as judged by the investigator and with more than 5 PLM/h during bedtime in each of three screening actigraphy nights. Patients must have given written informed consent in accordance with ICH-GCP and local legislation prior to participation in the study. Exclusion criteria: Patients with significant diseases other than restless legs syndrome will be excluded. A significant disease is defined as a disease that, which in the opinion of the investigator may put the patient at a risk because of the participation in the study, that may influence the result of the study or the patient's ability to participate or that is expected to relevantly reduce life expectancy. Patients with known hypersensitivity or contraindications to pramipexole, levodopa or benserazide or any other substances present in the study medications. Patients with iron-deficiency Patients with disabilities or other incapacities that preclude regular attendance at clinic for the study visits, and patients on a shift-work-schedule or who are otherwise unable to follow a regular sleep-wake cycle. Patients who have been previously treated with pramipexole or levodopa. Pregnant or nursing women or women of childbearing age who are at risk of pregnancy and are not willing to use adequate contraceptive methods (hormonal contraception or intrauterine devices) during the study period.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pramipexole|nan|
|Drug: levodopa in combination with benserazide|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of periodic limb movements while in bed (PLM-I) |  | after 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in RLS-score |  | after 4 weeks | 
| Changes in sleep quality as assessed in a sleep diary |  | after 4 weeks | 
| Changes in Quality of Life (SF-36) |  | after 4 weeks | 
| Mood changes measured by Hospital Anxiety and Depression Scale (HAD) |  | after 4 weeks | 
| Overall impression assessed by Clinical Global Impression (CGI) |  | after 4 weeks | 
| Changes in daytime sleepiness as assessed by the Epworth Sleepiness Scale (ESS) |  | after 4 weeks | 
| Incidence and Intensity of Adverse events |  | up to 10 weeks | 
| Changes in safety laboratory values |  | up to 10 weeks |