Phase IV Trial With Pramipexole to Evaluate Safety and Efficacy in Patients With RLS Associated With Mood Disturbances

A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With 0.125-0.75 mg/Day Pramipexole (Sifrol®, Mirapexin®) Orally for 12 Weeks to Investigate the Safety and Efficacy in Out-patients With Idiopathic Restless Legs Syndrome Associated With Mood Disturbances

The primary objective of this study is to determine the efficacy of pramipexole 0.125 mg to 0.75 mg daily versus placebo on RLS symptoms and on associated mood disturbances and depressive symptoms, after 12 weeks of treatment

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. In addition all of the following must be demonstrated at Visit 2 (baseline):

IRLS total score >15 A score of >=2 for item 10 of the IRLS rating scale

Exclusion Criteria:

1. Women of child-bearing potential who do not use an adequate method of contraception
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
5. All treatment less than 14 days before baseline or concomitant treatment with medication or dietary supplements, which could significantly influence RLS symptoms
6. Withdrawal symptoms of any medication must not be present at baseline
7. Previous pramipexole non-responders in other indications than RLS.
8. Hypersensitivity to pramipexole or any other component of the investigational product
9. Diagnosis of diabetes mellitus requiring insulin
10. Any of the following laboratory results at screening: clinically significant abnormalities at the investigatos discretion; Hb below lower limit of normal
11. Clinically significant renal disease at screening
12. Clinically significant hepatic disease at screening
13. Serum ferritin <10 ng/mL at screening.
14. History of/or malignant melanoma.
15. History of/or clinically significant vision abnormalities
16. History of/or any other sleep disorder
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, or BDI-II total score >28
18. History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigators opinion
19. History of/or alcohol abuse or drug addiction within the last 2 years before screening
20. Patients on a shift-work-schedule or otherwise unable to follow a regular sleep-wake cycle
21. Participation in an investigational drug study within one month prior to the start of this study
22. Patients with any clinically significant conditions that in the opinion of the investigator