For patients with severe restless legs syndrome (RLS), gabapentin enacarbil (GEn) was shown to significantly improve RLS symptoms and the consequences of these symptoms.
The findings come in a new meta-analysis which assessed data from three trials; XP052 (NCT00298623), XP053 (NCT00365352), and XP081 (NCT01332305). A total of 249 patients from these studies, with a baseline IRLS score of ≥24 (defined as severe restless legs syndrome), were included in the analysis. Patients were administered either placebo (n=85), GEn at 600mg dose (n=64), or GEn at 1200mg dose (n=100). Currently, GEn 1200mg is not approved to treat moderate-to-severe RLS.
Results showed significant improvements in IRLS scores associated with both GEn dose groups. After 12 weeks the LS (Least-square) mean change in total IRLS score from baseline was
–16.3 for the GEn 600mg group (P<0.01), –18.0 for the GEn 1200mg group (P<0.01), and –12.3 for the placebo group.
Significantly more patients with severe primary RLS treated with GEn 600mg (64%) and 1200mg (74%) were Clinical Global Impression – Improvement (CGI-I) survey (CGI-I) responders at week 12 versus placebo (42%; p < 0.01 for both GEn doses). By week 12, 63.8% and 74.4% responded feeling ‘much’ or ‘very much’ improved from the GEn 600mg and 1200mg dose groups, respectively. This is compared to 41.8% of the placebo group.
The researchers investigated a number of other results including sleep disruptions, quality of life (QoL), and mood outcomes. Post-sleep questionnaires showed that GEn 600mg individuals reported improvements in all items except overall quality of sleep, whereas members of the GEn 1200mg group reported improvements in all items when compared with placebo (P<0.05).
From data of the 248 severe RLS patients enrolled in studies XP052 and XP053 (placebo, n = 93; GEn 600 mg, n = 54; GEn 1200 mg, n = 101), significant RLS QoL improvements were reported. LS mean treatment differences at week 12 compared with placebo were −5.7 (2.86) for GEn 600mg, and −10.1 (2.40) for GEn 1200mg groups, with P<0.05 for both groups.
The GEn 1200mg group reported significantly improved fatigue-inertia, confusion-bewilderment, total mood disturbance, and vigor-activity compare with the placebo group at week 12. Similar improvements were not noted in the 600mg dose group, except during week 4 when confusion-bewilderment improved compared to placebo.
The authors of the analysis highlight how there have been few studies published focusing on treatments for severe RLS. The findings from their study show improvements with GEn (600mg and 1200mg) in a subgroup of patients with severe RLS (as defined by having a baseline IRLS score of ≥24), and improvements on a number of knock-on effects having RLS patients face.
Regarding the GEn dose of 1200mg not currently being FDA-approved, the authors write, “Several other clinical studies have described equivalent or superior effects of GEn 1200mg relative to GEn 600mg by numerical comparison in the treatment of RLS symptoms and sleep-related outcomes.” However, they point out that these results are based on patients experiencing the most severe types of RLS. The researchers conclude that more research is needed to further evaluate the efficacy of different GEn doses, “specifically in adult patients with severe primary RLS.”
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