A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome

Daniel O. Lee, Ronald B. Ziman, A. Thomas Perkins, J. Steven Poceta, Arthur S. Walters, Ronald W. Barrett, Fares J. Arguello, Eric M. Ball, Lisa Cohen, Michael J. Drass, Stephen Duntley, Mitchell D. Feller, Gerald J. Ferencz, Mark A. Fisher, James E. Garrison, John R. Huddlestone, Mark Ledoux, Kurt W. Lesh, Daniel G. Lorch, Stuart J. Menn & 9 others Leslie Moldauer, Charulatha P. Nagar, Thomas Perkins, Michael Rokeach, Richard Shubin, Daniel Vine, J. Catesby Ware, Charles Wells, Paul Wylie

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Abstract

Study Objective: To evaluate the efficacy and tolerability of gabapentin enacarbil (GEn) 1200 mg or 600 mg compared with placebo in subjects with moderate-to-severe primary restless legs syndrome (RLS). Methods: This 12-week, multicenter, double-blind, placebo-controlled study randomized subjects (1:1:1) to GEn 1200 mg, 600 mg, or placebo. Co-primary endpoints: mean change from baseline in International Restless Legs Scale (IRLS) total score and proportion of responders (rated as "very much" or "much" improved) on the investigator-rated Clinical Global Impression-Improvement scale (CGI-I) at Week 12 LOCF for GEn 1200 mg compared with placebo. Secondary endpoints included GEn 600 mg compared with placebo on the IRLS and CGI-I at Week 12 LOCF and subjective measures for sleep. Safety and tolerability assessments included adverse events. Results: 325 subjects were randomized (GEn 1200 mg = 113; 600 mg = 115; placebo = 97). GEn 1200 mg significantly improved mean [SD] IRLS total score at Week 12 LOCF (baseline: 23.2 [5.32]; Week 12: 10.2 [8.03]) compared with placebo (baseline: 23.8 [4.58]; Week 12: 14.0 [7.87]; adjusted mean treatment difference [AMTD]: -3.5; p = 0.0015), and significantly more GEn 1200 mg-treated (77.5%) than placebo-treated (44.8%) subjects were CGI-I responders (p < 0.0001). Similar significant results were observed with GEn 600 mg for IRLS (AMTD: -4.3; p < 0.0001) and CGI-I (72.8% compared with 44.8%; p < 0.0001). GEn also significantly improved sleep outcomes (Post-Sleep Questionnaire, Pittsburgh Sleep Diary and Medical Outcomes Sleep Scale) compared with placebo. The most commonly reported adverse events were somnolence (GEn 1200 mg = 18.0%; 600 mg = 21.7%; placebo = 2.1%) and dizziness (GEn 1200 mg = 24.3%; 600 mg = 10.4%; placebo = 5.2%). Dizziness increased with increased dose and led to discontinuation in 2 subjects (GEn 1200 mg, n = 1; GEn 600 mg, n = 1). Somnolence led to discontinuation in 3 subjects (GEn 600 mg). Conclusions: GEn 1200 mg and 600 mg significantly improve RLS symptoms and sleep disturbance compared with placebo and are generally well tolerated.

Original languageEnglish (US)
Pages (from-to)282-292
Number of pages11
JournalJournal of Clinical Sleep Medicine
Volume7
Issue number3
DOIs
StatePublished - Jun 15 2011

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Restless Legs Syndrome
Placebos
Sleep
1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
Dizziness

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Neurology
  • Clinical Neurology

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A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. / Lee, Daniel O.; Ziman, Ronald B.; Perkins, A. Thomas; Poceta, J. Steven; Walters, Arthur S.; Barrett, Ronald W.; Arguello, Fares J.; Ball, Eric M.; Cohen, Lisa; Drass, Michael J.; Duntley, Stephen; Feller, Mitchell D.; Ferencz, Gerald J.; Fisher, Mark A.; Garrison, James E.; Huddlestone, John R.; Ledoux, Mark; Lesh, Kurt W.; Lorch, Daniel G.; Menn, Stuart J.; Moldauer, Leslie; Nagar, Charulatha P.; Perkins, Thomas; Rokeach, Michael; Shubin, Richard; Vine, Daniel; Ware, J. Catesby; Wells, Charles; Wylie, Paul.

In: Journal of Clinical Sleep Medicine, Vol. 7, No. 3, 15.06.2011, p. 282-292.

Research output: Contribution to journalArticle

Lee, DO, Ziman, RB, Perkins, AT, Poceta, JS, Walters, AS, Barrett, RW, Arguello, FJ, Ball, EM, Cohen, L, Drass, MJ, Duntley, S, Feller, MD, Ferencz, GJ, Fisher, MA, Garrison, JE, Huddlestone, JR, Ledoux, M, Lesh, KW, Lorch, DG, Menn, SJ, Moldauer, L, Nagar, CP, Perkins, T, Rokeach, M, Shubin, R, Vine, D, Ware, JC, Wells, C & Wylie, P 2011, 'A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome', Journal of Clinical Sleep Medicine, vol. 7, no. 3, pp. 282-292. https://doi.org/10.5664/JCSM.1074
Lee, Daniel O. ; Ziman, Ronald B. ; Perkins, A. Thomas ; Poceta, J. Steven ; Walters, Arthur S. ; Barrett, Ronald W. ; Arguello, Fares J. ; Ball, Eric M. ; Cohen, Lisa ; Drass, Michael J. ; Duntley, Stephen ; Feller, Mitchell D. ; Ferencz, Gerald J. ; Fisher, Mark A. ; Garrison, James E. ; Huddlestone, John R. ; Ledoux, Mark ; Lesh, Kurt W. ; Lorch, Daniel G. ; Menn, Stuart J. ; Moldauer, Leslie ; Nagar, Charulatha P. ; Perkins, Thomas ; Rokeach, Michael ; Shubin, Richard ; Vine, Daniel ; Ware, J. Catesby ; Wells, Charles ; Wylie, Paul. / A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. In: Journal of Clinical Sleep Medicine. 2011 ; Vol. 7, No. 3. pp. 282-292.
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abstract = "Study Objective: To evaluate the efficacy and tolerability of gabapentin enacarbil (GEn) 1200 mg or 600 mg compared with placebo in subjects with moderate-to-severe primary restless legs syndrome (RLS). Methods: This 12-week, multicenter, double-blind, placebo-controlled study randomized subjects (1:1:1) to GEn 1200 mg, 600 mg, or placebo. Co-primary endpoints: mean change from baseline in International Restless Legs Scale (IRLS) total score and proportion of responders (rated as {"}very much{"} or {"}much{"} improved) on the investigator-rated Clinical Global Impression-Improvement scale (CGI-I) at Week 12 LOCF for GEn 1200 mg compared with placebo. Secondary endpoints included GEn 600 mg compared with placebo on the IRLS and CGI-I at Week 12 LOCF and subjective measures for sleep. Safety and tolerability assessments included adverse events. Results: 325 subjects were randomized (GEn 1200 mg = 113; 600 mg = 115; placebo = 97). GEn 1200 mg significantly improved mean [SD] IRLS total score at Week 12 LOCF (baseline: 23.2 [5.32]; Week 12: 10.2 [8.03]) compared with placebo (baseline: 23.8 [4.58]; Week 12: 14.0 [7.87]; adjusted mean treatment difference [AMTD]: -3.5; p = 0.0015), and significantly more GEn 1200 mg-treated (77.5{\%}) than placebo-treated (44.8{\%}) subjects were CGI-I responders (p < 0.0001). Similar significant results were observed with GEn 600 mg for IRLS (AMTD: -4.3; p < 0.0001) and CGI-I (72.8{\%} compared with 44.8{\%}; p < 0.0001). GEn also significantly improved sleep outcomes (Post-Sleep Questionnaire, Pittsburgh Sleep Diary and Medical Outcomes Sleep Scale) compared with placebo. The most commonly reported adverse events were somnolence (GEn 1200 mg = 18.0{\%}; 600 mg = 21.7{\%}; placebo = 2.1{\%}) and dizziness (GEn 1200 mg = 24.3{\%}; 600 mg = 10.4{\%}; placebo = 5.2{\%}). Dizziness increased with increased dose and led to discontinuation in 2 subjects (GEn 1200 mg, n = 1; GEn 600 mg, n = 1). Somnolence led to discontinuation in 3 subjects (GEn 600 mg). Conclusions: GEn 1200 mg and 600 mg significantly improve RLS symptoms and sleep disturbance compared with placebo and are generally well tolerated.",
author = "Lee, {Daniel O.} and Ziman, {Ronald B.} and Perkins, {A. Thomas} and Poceta, {J. Steven} and Walters, {Arthur S.} and Barrett, {Ronald W.} and Arguello, {Fares J.} and Ball, {Eric M.} and Lisa Cohen and Drass, {Michael J.} and Stephen Duntley and Feller, {Mitchell D.} and Ferencz, {Gerald J.} and Fisher, {Mark A.} and Garrison, {James E.} and Huddlestone, {John R.} and Mark Ledoux and Lesh, {Kurt W.} and Lorch, {Daniel G.} and Menn, {Stuart J.} and Leslie Moldauer and Nagar, {Charulatha P.} and Thomas Perkins and Michael Rokeach and Richard Shubin and Daniel Vine and Ware, {J. Catesby} and Charles Wells and Paul Wylie",
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TY - JOUR

T1 - A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome

AU - Lee, Daniel O.

AU - Ziman, Ronald B.

AU - Perkins, A. Thomas

AU - Poceta, J. Steven

AU - Walters, Arthur S.

AU - Barrett, Ronald W.

AU - Arguello, Fares J.

AU - Ball, Eric M.

AU - Cohen, Lisa

AU - Drass, Michael J.

AU - Duntley, Stephen

AU - Feller, Mitchell D.

AU - Ferencz, Gerald J.

AU - Fisher, Mark A.

AU - Garrison, James E.

AU - Huddlestone, John R.

AU - Ledoux, Mark

AU - Lesh, Kurt W.

AU - Lorch, Daniel G.

AU - Menn, Stuart J.

AU - Moldauer, Leslie

AU - Nagar, Charulatha P.

AU - Perkins, Thomas

AU - Rokeach, Michael

AU - Shubin, Richard

AU - Vine, Daniel

AU - Ware, J. Catesby

AU - Wells, Charles

AU - Wylie, Paul

PY - 2011/6/15

Y1 - 2011/6/15

N2 - Study Objective: To evaluate the efficacy and tolerability of gabapentin enacarbil (GEn) 1200 mg or 600 mg compared with placebo in subjects with moderate-to-severe primary restless legs syndrome (RLS). Methods: This 12-week, multicenter, double-blind, placebo-controlled study randomized subjects (1:1:1) to GEn 1200 mg, 600 mg, or placebo. Co-primary endpoints: mean change from baseline in International Restless Legs Scale (IRLS) total score and proportion of responders (rated as "very much" or "much" improved) on the investigator-rated Clinical Global Impression-Improvement scale (CGI-I) at Week 12 LOCF for GEn 1200 mg compared with placebo. Secondary endpoints included GEn 600 mg compared with placebo on the IRLS and CGI-I at Week 12 LOCF and subjective measures for sleep. Safety and tolerability assessments included adverse events. Results: 325 subjects were randomized (GEn 1200 mg = 113; 600 mg = 115; placebo = 97). GEn 1200 mg significantly improved mean [SD] IRLS total score at Week 12 LOCF (baseline: 23.2 [5.32]; Week 12: 10.2 [8.03]) compared with placebo (baseline: 23.8 [4.58]; Week 12: 14.0 [7.87]; adjusted mean treatment difference [AMTD]: -3.5; p = 0.0015), and significantly more GEn 1200 mg-treated (77.5%) than placebo-treated (44.8%) subjects were CGI-I responders (p < 0.0001). Similar significant results were observed with GEn 600 mg for IRLS (AMTD: -4.3; p < 0.0001) and CGI-I (72.8% compared with 44.8%; p < 0.0001). GEn also significantly improved sleep outcomes (Post-Sleep Questionnaire, Pittsburgh Sleep Diary and Medical Outcomes Sleep Scale) compared with placebo. The most commonly reported adverse events were somnolence (GEn 1200 mg = 18.0%; 600 mg = 21.7%; placebo = 2.1%) and dizziness (GEn 1200 mg = 24.3%; 600 mg = 10.4%; placebo = 5.2%). Dizziness increased with increased dose and led to discontinuation in 2 subjects (GEn 1200 mg, n = 1; GEn 600 mg, n = 1). Somnolence led to discontinuation in 3 subjects (GEn 600 mg). Conclusions: GEn 1200 mg and 600 mg significantly improve RLS symptoms and sleep disturbance compared with placebo and are generally well tolerated.

AB - Study Objective: To evaluate the efficacy and tolerability of gabapentin enacarbil (GEn) 1200 mg or 600 mg compared with placebo in subjects with moderate-to-severe primary restless legs syndrome (RLS). Methods: This 12-week, multicenter, double-blind, placebo-controlled study randomized subjects (1:1:1) to GEn 1200 mg, 600 mg, or placebo. Co-primary endpoints: mean change from baseline in International Restless Legs Scale (IRLS) total score and proportion of responders (rated as "very much" or "much" improved) on the investigator-rated Clinical Global Impression-Improvement scale (CGI-I) at Week 12 LOCF for GEn 1200 mg compared with placebo. Secondary endpoints included GEn 600 mg compared with placebo on the IRLS and CGI-I at Week 12 LOCF and subjective measures for sleep. Safety and tolerability assessments included adverse events. Results: 325 subjects were randomized (GEn 1200 mg = 113; 600 mg = 115; placebo = 97). GEn 1200 mg significantly improved mean [SD] IRLS total score at Week 12 LOCF (baseline: 23.2 [5.32]; Week 12: 10.2 [8.03]) compared with placebo (baseline: 23.8 [4.58]; Week 12: 14.0 [7.87]; adjusted mean treatment difference [AMTD]: -3.5; p = 0.0015), and significantly more GEn 1200 mg-treated (77.5%) than placebo-treated (44.8%) subjects were CGI-I responders (p < 0.0001). Similar significant results were observed with GEn 600 mg for IRLS (AMTD: -4.3; p < 0.0001) and CGI-I (72.8% compared with 44.8%; p < 0.0001). GEn also significantly improved sleep outcomes (Post-Sleep Questionnaire, Pittsburgh Sleep Diary and Medical Outcomes Sleep Scale) compared with placebo. The most commonly reported adverse events were somnolence (GEn 1200 mg = 18.0%; 600 mg = 21.7%; placebo = 2.1%) and dizziness (GEn 1200 mg = 24.3%; 600 mg = 10.4%; placebo = 5.2%). Dizziness increased with increased dose and led to discontinuation in 2 subjects (GEn 1200 mg, n = 1; GEn 600 mg, n = 1). Somnolence led to discontinuation in 3 subjects (GEn 600 mg). Conclusions: GEn 1200 mg and 600 mg significantly improve RLS symptoms and sleep disturbance compared with placebo and are generally well tolerated.

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