Medline ® Abstracts for References 28,29

A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). The patients were started on pramipexole 0.25 mg/day and were subsequently maintained on that dose or switched to 0.125, 0.5, or 0.75 mg/day to achieve optimal efficacy and tolerability. The International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (IRLS) score improved from 22.3+/-4.7 at baseline to 11.1+/-7.7 at week 8 and 4.9+/-5.9 at week 52. IRLS responders, defined as patients whose IRLS total score decreased by>or =50% from baseline, accounted for 67.4% at week 12 and 86.6% at week 52. Over 90% of patients were Clinical Global Impression-global improvement (CGI-I) and Patient Global Impression (PGI) responders. The Pittsburgh Sleep Quality Index (PSQI) score decreased from 7.9+/-3.1 at baseline to 4.6+/-2.9 at week 52. Similarly, the Japanese version of the Epworth Sleepiness Scale score decreased from 9.3+/-5.2 to 4.9+/-3.8. Baseline IRLS score<or =20 was significantly associated with a complete IRLS response in this long-term study. Adverse events were typical of nonergot dopamine agonists, mild in intensity, and decreased in frequency as the study progressed. RLS augmentation was not observed. Pramipexole 0.25-0.75 mg/day is efficacious, safe, and well tolerated in patients with RLS. Pramipexole showed good efficacy, particularly in patients with an IRLS total score<20.

BACKGROUND AND OBJECTIVE: To demonstrate the long-term efficacy and safety of pramipexole for Restless Legs Syndrome (RLS) using physician and patient RLS ratings, along with subjective assays of sleep parameters, in a 26-week, open-label trial.

PATIENTS AND METHODS: Among 107 Finnish adults with moderate to severe RLS, pramipexole initiated at 0.125 mg/day was titrated to a maximum 0.75 mg/day. Efficacy evaluations included the International RLS Study Group Rating Scale (IRLS), Patient Global Impression (PGI) scale, Clinical Global Impressions-Improvement (CGI-I) scale, Epworth Sleepiness Scale (ESS), and Short Form-36 (SF-36) Health Survey. Subjective Sleep Quality was assessed by patient ratings of sleep and morning tiredness. Safety was documented by Adverse Events reported in>5% of patients.

RESULTS: The mean reduction in IRLS score was 73.5% (P<0.05). The IRLS responder rate, defined by score reduction of>or= 50%, was 81.3%. On the PGI scale, 89.7% of patients rated themselves as "very much" or "much" better. By CGI-I assessment, 94.8% of patients were considered either "very much" or "much" improved. Mean ESS score showed a modest but statistically significant reduction (P<0.05) within the normal range, indicating that long-term pramipexole did not increase daytime sleepiness. On the SF-36 all 8 domains showed improvement, 5 of them statistically significant (P<0.05) and 4 of these 5 (role-physical, bodily pain, vitality, and role-emotional) by>10 points on a 100-point scale. Subjective Sleep Quality also improved. The most frequent Adverse Events were influenza (17.8%), headache (15.0%), and fatigue (10.3%).

CONCLUSION: Pramipexole is well tolerated and effective for long-term treatment of RLS.