Abstract
Purpose
Few studies have investigated restless legs syndrome (RLS) treatment effects on individual
International RLS Study Group Rating Scale (IRLS) items. We assessed the effects of
gabapentin enacarbil (GEn) on individual IRLS items and their correlation with sleep
disturbances in adults with moderate-to-severe primary RLS.
Methods
Data were pooled from the randomized, double-blind, placebo-controlled, 12-week studies
of XP052, XP053, and XP081 for adults who received GEn (600 or 1200 mg) or placebo
once daily. Adults had primary RLS, IRLS total score ≥15, and RLS symptoms >15 days
during the month before screening and for ≥4 of the 7 consecutive evenings at baseline.
End points included mean change from baseline to week 12 in individual IRLS and post-sleep
questionnaire (PSQ) items. For IRLS items, least squares mean treatment differences
were calculated from a mixed model for repeated measures. For PSQ items, Cochran–Mantel–Haenszel
row mean scores tests with integer scoring were used. Correlations between IRLS and
PSQ items were assessed by Spearman’s rank coefficients. Safety profile outcomes included
treatment-emergent adverse events (TEAEs) and serious TEAEs.
Findings
The modified intent-to-treat population included 671 patients (GEn 600 mg = 161; GEn
1200 mg = 266; placebo = 244). GEn significantly improved mean [SE] differences versus
placebo for all IRLS items at week 12, including severity of sleep disturbance (GEn
600 mg, −0.4 [0.10]; GEn 1200 mg, −0.4 [0.09]), daytime tiredness (−0.4 [0.09]; −0.4
[0.08]), RLS severity (−0.4 [0.10]; −0.3 [0.08]), impact on daily affairs (−0.3 [0.07];
−0.3 [0.07]), and mood disturbance (−0.2 [0.07]; −0.3 [0.06]); all P<0.001). For PSQ items, significant (P<0.01) improvements occurred with both GEn doses versus placebo at week 12. The correlations
between IRLS and PSQ items for change from baseline to week 12 were moderate to strong,
and all correlations were significant (P<0.001). The most frequent TEAEs were somnolence (GEn 600 mg, 20%; GEn 1200 mg, 23%;
placebo, 5%) and dizziness (GEn 600 mg, 14%; GEn 1200 mg, 22%; placebo, 5%).
Implications
GEn significantly improved individual IRLS items and sleep disturbance versus placebo.
Correlations between IRLS and PSQ items were moderate to strong. This was not a formal
meta-analysis and was not powered to compare the GEn doses. Nevertheless, our study
finds that the benefits of GEn extend to individual IRLS items and supports the importance
of sleep quality in RLS treatment. ClinicalTrials.gov identifiers: NCT00298623, NCT00365352,
and NCT01332305.
Key words
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Article info
Publication history
Published online: June 07, 2016
Accepted:
May 11,
2016
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
