The Effect of Gabapentin Enacarbil (GEn) on Pain Outcomes and Restless Legs Syndrome (RLS) Symptoms in Adults with Moderate-to-Severe Primary RLS: Pooled Analyses from 3 Randomized Controlled Trials

Authors: Aaron Ellenbogen, Richard Boortz-Marx, Richard Bogan, Cheryl Faber, Mark Jaros, Richard Kim, Gwendoline Shang

Affiliations: Michigan Institute for Neurological Disorders, Farmington Hills, MI; Duke University School of Medicine, Department of Anesthesiology, Division of Pain Medicine, Durham, NC; SleepMed, Columbia, SC; Neurology Associates, St. Louis, MO; Summit Analytical, LLC, Denver, CO; XenoPort, Inc., Santa Clara, CA

Introduction: This pooled analysis explored whether adults with moderate-to-severe primary RLS experienced improved pain and RLS symptoms when treated with GEn. Pain and International Restless Legs Scale (IRLS) total score correlations were investigated.

Methods: Data were pooled by GEn (600 mg or 1200 mg) and placebo groups for 3 previous trials. Patients with baseline IRLS total score ≥15 and pain score ≥4 were included. Pain responders had a ≥30% pain score improvement on a numeric rating scale, typically considered a notable improvement. IRLS total score responders had a score <15 with an improvement from baseline ≥6 at week 12, as defined previously. Spearman rank correlation coefficients were calculated.

Results: 366/671 patients met analysis entry criteria (placebo, n=133; GEn 600 mg, n=86; GEn 1200 mg, n=147). Most patients were joint responders for pain and IRLS total score (placebo, 40%; GEn 600 mg, 70%; GEn 1200 mg, 67%) and some were not responders in either category (35%; 16%; 18%, respectively). Few patients were responders only for pain (placebo, 16%; GEn 600 mg, 9%; GEn 1200 mg, 12%) or IRLS total score (9%; 5%; 4%, respectively). Differences across all 4 categories were significant between GEn 600 mg vs placebo (Chi Square, P=.0003) and GEn 1200 mg vs placebo (Chi Square, P<.0001). Moderate to strong correlations were observed between IRLS total score and pain score for change from baseline to week 12 (placebo, 0.69; GEn 600 mg, 0.54; GEn 1200 mg, 0.68; all P<.0001). The most common treatment-emergent adverse events in the individual studies were somnolence and dizziness.

Conclusion: In this pooled analysis, most patients were joint responders for pain and IRLS total score, and more GEn-treated patients (600 mg and 1200 mg) had a joint response vs placebo. There were significant correlations between the change from baseline in pain and IRLS total score.

Support: These studies and this analysis were conducted by XenoPort, Inc., Santa Clara, CA. Medical writing support was provided by CodonMedical, a division of KnowledgePoint360 (an Ashfield Company), and was funded by XenoPort, Inc.

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Association Between Pain and Symptoms of Restless Legs Syndrome (RLS) in Adults with Moderate-to Severe Primary RLS in a Combined Treatment Population: Pooled Analyses from 3 Randomized Controlled Trials

Authors: Gordon Irving, Enrico Fazzini, John Fritz, Cheryl Faber, Mark Jaros, Richard Kim, Gwendoline Shang

Affiliations: Swedish Medical Center, Seattle, WA; NYU Medical Center, New York, NY; Hudson Primary Care, Jersey City, NJ; Neurology Associates St. Louis, MO; Summit Analytical, LLC, Denver, CO; XenoPort, Inc., Santa Clara, CA

Introduction: We explored associations between pain and RLS symptoms in adults with moderate-to severe primary RLS treated with gabapentin enacarbil (GEn) or placebo. Correlations between pain and International Restless Legs Scale (IRLS) total and individual item scores were investigated.

Methods: Data from three randomized trials were pooled across treatment groups (GEn 600 mg, GEn 1200 mg, placebo). This analysis included patients with baseline IRLS total score ≥15 and pain score ≥4. IRLS total score response was defined as a decrease in score of ≥6 and total score <15 at week 12. Pain response was defined as ≥30% improvement on a numerical rating scale, typically considered a notable improvement. Joint responders met both criteria. Spearman rank correlation coefficients were calculated.

Results: 366/671 patients met analysis entry criteria (placebo, n=133; GEn 600 mg, n=86; GEn 1200 mg, n=147). For all 3 groups combined, 58% of patients were joint responders for pain and IRLS total score, 24% were not responders in either category, 13% were only pain responders, and 6% were only IRLS total score responders. For change from baseline to week 12, there was a significant correlation between IRLS total score and pain score (0.70; P<.0001). There were moderate to strong correlations between pain score and IRLS items 1 (overall RLS discomfort, 0.62), 2 (overall need to move, 0.67), and 6 (RLS severity as a whole, 0.65; all P<.0001). All other IRLS items had weaker correlations with pain score. The most common treatment-emergent adverse events in the individual studies were somnolence and dizziness.

Conclusion: In this pooled analysis, most patients had a joint response for pain and RLS symptoms according to IRLS total score and pain score. There were significant correlations between pain and IRLS total score and individual item scores. These findings suggest that RLS symptoms and pain may be clinically related.

Support: These studies and this analysis were conducted by XenoPort, Inc., Santa Clara, CA. Medical writing support was provided by CodonMedical, a division of KnowledgePoint360 (an Ashfield Company), and was funded by XenoPort, Inc.

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