A Phase IV Trial With Pramipexole to Investigate the Effects on RLS Symptoms and Sleep Disturbance in Patients With RLS

A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With Pramipexole (Sifrol®, Mirapexin®) 0.125-0.75 mg/Day Per os for 12 Weeks to Investigate the Effects on RLS Symptoms (IRLS) and Sleep Disturbance (MOS Sleep Scale) in Out-patients With Idiopathic Restless Legs Syndrome

The primary objective of this study is to investigate the effects on RLS symptoms and sleep disturbance of pramipexole (Mirapexin) 0.125 mg/day to 0.75 mg/day per os for 12 weeks, compared to placebo, in the treatment of patients with idiopathic Restless Legs Syndrome

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 aged 18-80 years.

3. Diagnosis of idiopathic RLS according to the clinical RLS criteria of the IRLSSG [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 prior to baseline (Visit 2).

5. IRLS total score >15 at baseline (Visit 2).

Exclusion Criteria:

1. Women of child-bearing potential who do not use during the trial an adequate method of contraception.

2. Women of child-bearing potential not having negative pregnancy test at screening.

3. Breastfeeding women.

4. Concomitant or previous pharmacologic therapy for RLS with: dopamine agonists or levodopa (within 14 days prior to baseline), levodopa with augmentation, unsuccessful prior treatment with non-ergot dopamine agonists.

5. All treatment less than 14 days or concomitant treatment with medication or dietary supplements which could significantly influence RLS symptoms.

6. Withdrawal symptoms.

7. 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. Diabetes mellitus requiring insulin therapy.

10. Any of the following laboratory results at screening:

    • any clinically significant abnormalities in laboratory parameters;
    • haemoglobin below LLN.

11. Clinically significant renal disease or calculated creatinine clearance lower than 30 mL/minute.

12. Clinically significant hepatic disease or GPT >2 times the ULN.

13. Serum ferritin <10 ng/mL.

14. History of/or malignant melanoma.

15. History of/or clinically significant vision abnormalities.

16. History of/or any other sleep disorder (other than RLS-related).

17. History of/or major depressive disorder or any psychotic disorder, mental disorders or any present Axis I psychiatric disorder according to DSM IV requiring any medical therapy.

18. History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigator's opinion.

19. History of/or alcohol abuse or drug addiction (within 2 years).

20. Patients on a shift-work-schedule or who are otherwise unable to follow a regular sleep-wake cycle.

21. Participation in an investigational drug study within one month.

22. Any clinically significant conditions that would interfere or constitute a health hazard for the patient.