A 6 Week Trial to Study the Efficacy and Safety of a Starting Dose 0.25 mg Pramipexole (Mirapex) in Patients With RLS

This trial is a 6-week, double-blind, randomized, active and placebo-controlled parallel-group study with a primary objective of comparison of starting doses of pramipexole fixed-dose (0.25 mg daily) and pramipexole titrated-dose (0.125 mg qd for 1 week, then 0.25 mg qd for the remaining 5 weeks) with placebo to evaluate efficacy and safety in treating RLS symptoms in patients diagnosed with idiopathic RLS.

The secondary objectives of this study will be to assess the onset of action of symptomatic relief of RLS for pramipexole with daily assessment of PGI and modified IRLS during two intervals of the first 2 weeks (Days 2, 3 and 4 and Days 9, 10, and 11) and assessment of IRLS, PGI and CGI-I at Weeks 1, 2, 4 and 6 (CGI-I additionally on Day 3).

Inclusion Criteria:

1. Written informed consent consistent with ICH-GCP and local IRB/IEC requirements obtained prior to any study procedures being performed and the ability and willingness to comply with study treatment regimen and to attend study assessments.
2. Male or female out-patients 18 to 80 years of age.

3. Diagnosis of idiopathic RLS according to the clinical RLS criteria revised by the IRLSSG in collaboration with the U.S.A. National Institutes of Health [P03-03355]. All four criteria must be present to fulfil the diagnosis of RLS:

   - An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. (Sometimes the urge to move is present without the uncomfortable sensations and sometimes the arms or other body parts are involved in addition to the legs).

   The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.

   • The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
   • The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night. (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present).
4. RLS symptoms present at least 2 to 3 days per week during the last 3 months.
5. IRLS rating scale score >15 at baseline (Visit 2).

Exclusion Criteria:

1. Women of child-bearing potential (i.e., premenopausal women, or postmenopausal women less than 6 months after last menses) who do not use during the clinical trial an adequate method of contraception such as: double barrier protection (e.g., diaphragm or condom and spermicide), intrauterine device, hormonal therapy (oral, injectable, or subcutaneous), or partners surgical sterilization.
2. Any women of child-bearing potential not having negative pregnancy test at screening.
3. Breastfeeding women.

4. Concomitant or previous pharmacologic therapy for RLS as follows:

   • Any intake of dopamine agonists within 14 days prior to baseline (Visit 2).
   • Any intake of L-dopa within 14 days prior to baseline (Visit 2).
   • Any intake of L-dopa prior to baseline visit, if augmentation in RLS symptoms was observed.
   • Unsuccessful prior treatment with non-ergot dopamine agonists (e.g., pramipexole, ropinirole).
5. All treatment less than 14 days before baseline (Visit 2) or concomitant treatment with medication or dietary supplements which could significantly influence RLS symptoms, e.g., dopaminergic (other than levodopa and dopamine agonists) or antidopaminergic drugs, non-selective MAO inhibitors, sympathomimetics, neuroleptics, antidepressants, hypnotics, any benzodiazepines, antiepileptics, opioids, clonidine, ferrous salts, magnesium, folic acid, vitamin B12, antihistaminics, lithium, metoclopramide.
6. Withdrawal symptoms of any medication must not be present at baseline (Visit 2).
7. Previous pramipexole non-responders in other indications than RLS.
8. Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets.
9. Confirmed diagnosis of diabetes mellitus requiring insulin therapy.

10. Any of the following lab results at screening:

    • Patients with any clinically significant abnormalities in laboratory parameters at screening at the investigators discretion.
    • Haemoglobin (Hb) below lower limit of normal (LLN).