OBJECTIVE: This study evaluated the dose-related efficacy and safety of 
pregabalin in patients with idiopathic restless legs syndrome (RLS).
METHODS: This six-arm, double-blind, placebo-controlled, dose-response study 
randomized patients (N=137) with moderate-to-severe idiopathic RLS in an equal 
ratio to placebo or pregabalin 50, 100, 150, 300, or 450 mg/day. The 
dose-response was characterized using an exponential decay model, which 
estimates the maximal effect (E(max)) for the primary endpoint, the change in 
the International Restless Legs Study Group Rating Scale (IRLS) total score from 
baseline to week 6 of treatment. Secondary outcomes included Clinical Global 
Impressions-Improvement Scale (CGI-I) responders, sleep assessments, and safety.
RESULTS: The separation of treatment effect between placebo and pregabalin began 
to emerge starting at week 1 which continued and increased through week 6 for 
all dose groups. The IRLS total score for pregabalin was dose dependent and well 
characterized for change from baseline at week 6. The model estimated 50% 
(ED(50)) and 90% (ED(90)) of the maximal effect in reducing RLS symptoms that 
occurred at pregabalin doses of 37.3 and 123.9 mg/day, respectively. A higher 
proportion of CGI-I responders was observed at the two highest doses of 
pregabalin (300 and 450 mg/day) versus placebo. Dizziness and somnolence were 
the most common adverse events and appeared to be dose-related.
CONCLUSIONS: In this 6-week phase 2b study, pregabalin reduced RLS symptoms in 
patients with moderate-to-severe idiopathic RLS. The symptom reduction at week 6 
was dose-dependent with 123.9 mg/day providing 90% efficacy. Pregabalin was safe 
and well tolerated across the entire dosing range.