BALTIMORE, Md.—Patients with restless legs syndrome (RLS) reported significantly less pain after treatment with gabapentin enacarbil, a nondopaminergic therapy under investigation for this neurological condition, compared with placebo. This double-blind, randomized trial enrolled patients ≥18 years with RLS and an International Restless Leg Syndrome (IRLS) score ≥15 at Visit 1 (baseline) and Visit 2 (Day 1), a body mass index (BMI) ≤34kg/m2, and an estimated creatinine clearance ≥60mL/min.
Every day at 5:00 PM for 12 weeks, patients received gabapentin enacarbil 1200 mg (n=113), gabapentin enacarbil 600 mg (n=115) or placebo (n=97), with food. Using an 11-point scale (0=no pain and 10=most intense pain imaginable), patients recorded “pain associated with RLS” over the previous 24 hours for 7 days prior to baseline and at weeks 2, 4, 8, and 12. Treatment-emergent adverse events (TEAEs) were also assessed.
Co-primary end points were mean change from baseline in total score on the IRLS Rating Scale and proportion of those responding on the investigator-rated Clinical Global Impression-Improvement scale for the gabapentin enacarbil 1200 mg dose at week 12, Daniel Lee, MD, of East Carolina Neurology, Inc., Greenville, NC, and colleagues, noted. Efficacy of gabapentin enacarbil 600 mg was evaluated as a secondary end point.
Compared with placebo at week 12, patients treated with gabapentin enacarbil 1200 mg demonstrated significant improvement in mean IRLS Rating Scale total scores from baseline (-13.0 vs -9.8; P=0.0015). Additionally, significantly more patients treated with gabapentin enacarbil 1200 mg were responders by the Clinical Global Impression-Improvement scale (77.5% vs 44.8%; P<0.0001). Similar results were observed for the gabapentin enacarbil 600 mg dose.
Gabapentin enacarbil 1200 mg significantly reduced mean pain scores from baseline to week 12 vs placebo. For those with average daily pain scores >0 at baseline or week 12 (91% of patients), this reduction was -2.6 vs -1.7 (P=0.0015); for the gabapentin enacarbil 600 mg dose, reduction was -2.5 compared with -1.7 for placebo (P=0.0029). Those with baseline pain scores ≥4 (57% of patients) had a reduction of -3.5 with the gabapentin enacarbil 1200 mg dose vs -2.3 for placebo (P=0.0054) and -3.5 for the gabapentin enacarbil 600 mg dose vs -2.3 for placebo (P=0.0084).
Significantly more patients treated with gabapentin enacarbil 1200 mg reported a ≥50% reduction in pain from baseline compared to placebo at Week 12 (60.0% vs 44.1%; P=0.0253); results were similar for the gabapentin enacarbil 600 mg group (55.9% vs 44.1%; P=0.0997). For both dose groups, there was no significant treatment difference among patients with average daily pain scores ≥4 at baseline.
Most common TEAEs were dizziness, reported by 24% of patients in the gabapentin enacarbil 1200 mg group and 10% in the 600 mg group compared with 5% of those receiving placebo; and somnolence, reported by 18%, 22%, and 2%, respectively, the investigators told The American Pain Society’s 29th Annual Scientific Meeting attendees.