A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome

• Published in: Sleep medicine 2010-06, Vol.11 (6), p.512-519
• Main Authors: Allen, Richard, Chen, Crystal, Soaita, Adina, Wohlberg, Christopher, Knapp, Lloyd, Peterson, Barry T, García-Borreguero, Diego, Miceli, Jeffrey
• Format: Article
• Language: English
• Subjects: Actigraphy; Adult; Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Clinical study; Dose-Response Relationship, Drug; Dose–response; Double-Blind Method; Female; gamma-Aminobutyric Acid - adverse effects; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - therapeutic use; Humans; International Restless Legs Study Group Rating Scale; Male; Middle Aged; Neurology; Patient Satisfaction; Pregabalin; Restless legs syndrome; Restless Legs Syndrome - drug therapy; Sensorimotor disorder; Sleep - drug effects; Sleep duration; Sleep Medicine; Treatment Outcome; Wakefulness - drug effects
• ISSN: 1389-9457; 1878-5506
• DOI: 10.1016/j.sleep.2010.03.003

Abstract 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 ( Emax ) 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% (ED50 ) and 90% (ED90 ) 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.