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Pramipexole delivered sustained efficacy in clinical trial of patients with Restless Legs Syndrome

December 12, 2005

Two large, randomised, placebo-controlled studies presented at the inaugural conference of the World Association of Sleep Medicine (WASM; Berlin, Germany) in October demonstrate that pramipexole delivered both short-term and sustained efficacy in patients suffering from Restless Legs Syndrome (RLS)1,2 enrolled in these trials.

New data from a randomized, placebo-controlled "withdrawal" study1 show that discontinuation of pramipexole leads to rapid worsening of RLS in patients who had previously responded well to pramipexole therapy. In this study, RLS patients who responded to pramipexole treatment in a preceding 6-month open label treatment phase were randomized to receive either blinded pramipexole (n=78) or placebo (n=69) for 12 weeks. The primary endpoint of the study was assessment of 'Time to Worsening' of RLS symptoms measured using the International RLS Rating Scale (IRLS) and the Clinical Global Impressions - Global Improvement (CGI-I) scale. The results showed:

- RLS patients who were randomized to continue treatment with pramipexole experienced a significantly longer time before their symptoms worsened than those patients who were randomised to placebo (p<0.0001)
- The proportion of patients that experienced worsening of their RLS symptoms in the blinded pramipexole group was statistically significantly smaller compared to those randomized to receive placebo (pramipexole 20.5 percent vs. placebo 85.5 percent; p<0.0001)
- One week after randomization, more than 70.0 percent of patients on placebo worsened as compared to just 9.0 percent of patients in the blinded pramipexole group
- Pramipexole also significantly improved the disease-specific quality of life score to 90 percent (70 percent for placebo; p<0.0001)

In addition, in a fixed-dose study pramipexole demonstrated significant improvement in symptoms of RLS, when measured by two standard clinical assessment tools, when compared to placebo.2 This 12-week, placebo-controlled, randomized study sought to compare the efficacy and safety of pramipexole at different doses (0.25mg; 0.5mg and 0.75mg) when compared to placebo. After 12 weeks, patients who received pramipexole-across all three doses-experienced significantly greater improvements in symptoms of RLS compared to placebo. Three hundred and forty five patients were randomized and 339 patients were assessed at the end of 12 weeks for improvement in RLS symptoms using the IRLS and CGI-I scales.

- IRLS scores at week 12 demonstrated that across all three pramipexole doses the IRLS score was significantly improved for patients when compared to placebo
- CGI-I scores also demonstrated that significantly more patients who received pramipexole treatment reported themselves as 'much improved' or 'very much improved' at the end of 12 weeks of treatment compared to patients treated with placebo

In both studies pramipexole was generally well-tolerated and the most frequent adverse events were nausea, headache and fatigue.

Previous studies in RLS have reported rapid, statistically significant effects of pramipexole on RLS symptoms. The efficacy and safety of pramipexole for treatment of RLS has been studied from a starting dose of 0.125mg single dose per day and up to 0.75mg single dose per day.

These trials are part of a comprehensive clinical trial program, involving more than 1,000 patients, to assess the therapeutic potential of pramipexole in the treatment of RLS. Boehringer Ingelheim, the discoverer of the molecule, has also recently submitted applications for international regulatory approval of pramipexole in the treatment of RLS.

Ketchum