Gabapentin enacarbil improves pain associated with Restless Legs Syndrome (RLS)

Gabapentin enacarbil in subjects with moderate to severe primary restless legs syndrome with and without severe sleep disturbance: an integrated analysis of subjective and novel sleep endpoints from two studies

“…This was demonstrated by results from the MOS Sleep Scale, with a significant improvement in all domains; the PSQ, with significant improvement in sleep quality (both the moderate to no sleep disturbance and the very severe to severe sleep disturbance groups), as well as nighttime awakenings and hours awake per night (very severe to severe sleep disturbance group only); and the PghSD, with significant improvement in WASO. The MOS Sleep Scale and PghSD results confirm those already reported in the individual studies; 13,14 for the PSQ, the individual studies reported significant improvements for GEn 1200 mg and 600 mg compared with placebo on all items. 13,14 It is unsurprising that subjects with very severe to severe sleep disturbance at baseline reported less ST and TST and longer TAN and WASO on the 24-Hour RLS Symptom Diary and PghSD at baseline compared with subjects with moderate to no sleep disturbance.…”

“…gov identifier NCT00365352), 16 conducted at 28 centers in the USA, subjects were randomized to receive GEn 600 mg, 1200 mg, or placebo. 14 In both studies, GEn or placebo was administered once daily at 5 pm with food; GEn was initiated at a dose of 600 mg with subsequent titration to 1200 mg after 3 days. At the end of the study or at early termination (ET), subjects receiving GEn 1200 mg had their dose tapered over 7 days.…”

“…Key inclusion and exclusion criteria were similar for each study and have been described previously. 13,14 Briefly, the studies included adults with moderate to severe primary RLS as per International Restless Legs Syndrome Study Group diagnostic criteria, with RLS symptoms for $15 days during the month prior to screening and for $4 nights during the 7-day baseline period, and with a total IRLS score of $15 at baseline. Exclusion criteria included secondary RLS, a history of RLS symptom augmentation, or rebound with previous dopamine agonist treatment, and neurologic, sleep, or movement disorders other than RLS.…”

“…9 The efficacy and tolerability of GEn in adults with moderate to severe primary RLS have been demonstrated in two Phase III, 12-week, multicenter, placebo-controlled, randomized clinical trials. 13,14 These showed that, compared with placebo, treatment with GEn 600 mg (Study XP053) 14 and 1200 mg (Studies XP052 and XP053) 13,14 is associated with significant improvements in both restlessness and sleep disturbance, as measured using established tools such as the International Restless Legs Scale (IRLS), which measures specific RLS-related symptoms and symptom impact; the Clinical Global Impression -Improvement (CGI-I) scale, which assesses global change in condition; the Medical Outcomes Study (MOS) Sleep Scale, which provides a general measure of several sleep domains; the Post Sleep Questionnaire (PSQ), which evaluates sleep disturbance in RLS; and the Pittsburgh Sleep Diary (PghSD), which quantifies sleep and waking behaviors. GEn 600 mg is the daily dose approved by the US Food and Drug Administration for the treatment of moderate to severe primary RLS in adults.…”

“…In both Studies XP052 and XP053, GEn-treated groups showed a delayed time of onset of RLS symptoms within the 24-hour period compared with placebo groups, as well as a higher percentage of symptom-free subjects. 13,14 Here, we present a retrospective integrated analysis of Studies XP052 and XP053, assessing subjective sleep outcomes and the tolerability of once-daily GEn 1200 mg using pooled data from the two trials. The objective of such analysis was two fold: first to evaluate -using data pooled according to severity of sleep disturbance at study entrywhether baseline sleep disturbance could have an effect on sleep outcomes, as the interaction between treatment effect and baseline sleep disturbance was not assessed in the original studies; second, to assess how informative two novel sleep endpoints derived from the 24-Hour RLS Symptom Diary were.…”