Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study.

Background and purpose: To evaluate the effects of pramipexole (0.125‐0.75 mg/d) on polysomnographic (PSG) measures and patient and clinician ratings of restless legs syndrome (RLS). Patients and methods: Patients (nZ109) with moderate to severe RLS were randomized to placebo or fixed doses of pramipexole during a 3-week, double-blind, placebo-controlled, dose-finding study. Results: In each pramipexole dose group, the periodic limb movements during time in bed index (PLMI) decreased significantly, compared with placebo (adjusted mean difference in log-transformed data: 0.125 mg, K1.54; 0.25 mg, K1.93; 0.50 mg, K1.89; and 0.75 mg, K1.52; P!0.0001). At all doses, International RLS Study Group Rating Scale (IRLS) scores were also significantly reduced, with the greatest adjusted mean reduction in the 0.50 mg group (K17.01). At all but the lowest pramipexole dose, the percentage of responders (R50% reduction of IRLS score) was substantially higher than for placebo (61.9‐77.3, vs 33.3%). In the pramipexole groups, 50.0‐77.3% of patients rated their condition as ‘much better’ or ‘very much better’, compared with 38.1% of patients in the placebo group (PZ0.0139 for the 0.50 mg dose). Clinical global impressions (CGI) scale ratings of ‘much improved’ or ‘very much improved’ were given to 61.9‐86.4% of patients in the pramipexole groups, compared with 42.9% in the placebo group (P!0.05 for the 0.25, 0.50, and 0.75 mg groups). Pramipexole was well tolerated and did not produce somnolence at any dose.