TY - JOUR
T1 - Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome
T2 - Pooled Analysis of 3 Randomized Trials
AU - Ahmed, Mansoor
AU - Hays, Ryan
AU - Steven Poceta, J.
AU - Jaros, Mark J.
AU - Kim, Richard
AU - Shang, Gwendoline
N1 - Funding Information:
These studies and this analysis were conducted by XenoPort, Inc, Santa Clara, Calif. Drs. Ahmed and Hays have no conflicts to disclose. Dr. Poceta is on the speakers’ bureau for Teva and XenoPort, Inc. Dr. Jaros is a paid consultant of XenoPort, Inc. Drs. Kim and Shang are employees of and own stock in XenoPort, Inc. Medical writing support was provided by CodonMedical, an Ashfield Company, part of UDG Healthcare plc, and was funded by XenoPort, Inc. The authors have indicated that they have no other conflicts of interest regarding the content of this article.
Publisher Copyright:
© 2016 Elsevier HS Journals, Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - International Restless Legs Study Group Rating Scale
KW - gabapentin enacarbil
KW - post-sleep questionnaire
KW - restless legs syndrome
KW - sleep
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U2 - 10.1016/j.clinthera.2016.05.008
DO - 10.1016/j.clinthera.2016.05.008
M3 - Article
C2 - 27288210
AN - SCOPUS:84973572577
SN - 0149-2918
VL - 38
SP - 1726-1737.e1
JO - Clinical Therapeutics
JF - Clinical Therapeutics
IS - 7
ER -