Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS)

A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With Pramipexole (Sifrol, Mirapexin) 0.125-0.75 mg/Day Per os to Investigate the Long-term Efficacy, Safety and Tolerability in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome for 26 Weeks Followed by a 26 Week Open-label Extension Treatment Period

The primary objective of the current study will be the evaluation of long-term efficacy of a 26-weeks treatment with pramipexole in patients with idiopathic moderate to severe Restless Legs Syndrome (RLS) in comparison to placebo.

The key secondary objectives are to assess the effects on clinical global impressions - global improvement (CGI-I) (based on CGI-I responder rate) and on RLS (based on IRLS responder rate) for 26 weeks under pramipexole in comparison to placebo. Further secondary objectives are to investigate the incidence and severity of augmentation and rebound and to assess the effects on patient global impression (PGI) (based on PGI responder rate), on RLS symptoms (based on the RLS-6 scales), on associated mood disturbance (based on item 10 of the IRLS), on pain in limbs (based on a visual analogue scale (VAS)), on quality of life in RLS (based on Johns Hopkins RLS-QoL), on general quality of life Short Form 36 (SF-36) and on safety (based on adverse events (AE) profile) of pramipexole in comparison to placebo.

Inclusion Criteria:

1. Written informed consent consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local Institutional Review Board/Independent Ethics Committee (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 18-85 years
3. Diagnosis of idiopathic RLS according to the clinical RLS criteria of the International Restless Legs Syndrome Study Group (IRLSSG) [P03-03355]. All four criteria must be present to fulfil the diagnosis of RLS.
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 (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 partner's surgical sterilization
2. Any woman of child-bearing potential not having a negative pregnancy test at screening
3. Breastfeeding women
4. Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets
5. Diagnosis of augmentation under previous pharmacological RLS treatment
6. Concomitant or previous pharmacologic therapy as follows: Any intake of dopamine agonists within 14 days prior to baseline (Visit 2); Any intake of levodopa within 14 days prior to baseline (Visit 2); Unsuccessful prior treatment with non-ergot dopamine agonists (e.g. pramipexole, ropinirole);