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Oral gabapentin enacarbil is approved in adult patients for the treatment of moderate to severe primary restless legs syndrome (RLS) [featured indication] and the management of postherpetic neuralgia. In the 12-week Patient Improvements in Vital Outcomes following Treatment (PIVOT) RLS I and II trials in adult patients with moderate to severe primary RLS (n > 500 total evaluable), once-daily gabapentin enacarbil 600 or 1,200 mg significantly improved mean International Restless Legs Scale (IRLS) total scores compared with placebo, with significantly higher investigator-rated Clinical Global Impression-Improvement (CGI-I) responder rates in gabapentin enacarbil groups than in placebo groups. Improvements in other sleep outcomes (assessed using various scales) also generally favoured gabapentin enacarbil treatment. These data are supported by results from a polysomnography, crossover (two 4-week treatment periods) trial (n > 100 evaluable). Improvements in RLS symptoms with gabapentin enacarbil were maintained in a 52-week extension study of clinical trials, including PIVOT RLS I and II. The longer-term efficacy of gabapentin enacarbil in patients with moderate to severe RLS was also demonstrated in the 36-week PIVOT RLS Maintenance study and a 52-week noncomparative study conducted in Japan. Gabapentin enacarbil was generally well tolerated in adult patients with RLS participating in short- and longer-term clinical trials. The most common treatment-emergent adverse events were somnolence/sedation and dizziness. Most adverse events were of mild to moderate severity, with relatively few patients discontinuing treatment because of an adverse event.
- 5.National Institute of Neurological Disorders and Stroke. Restless legs syndrome fact sheet [online]. Available from URL: http://www.ninds.nih.gov/disorders/restless_legs/detail_restless_legs.htm. Accessed 15 Oct 2012.
- 6.Cundy KC, Branch R, Chernov-Rogan T, et al. XP13512 [(±)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion and transport by intestinal solute transporters. J Pharmacol Exp Ther. 2004;311(1):315–23.PubMedCrossRefGoogle Scholar
- 7.GlaxoSmithKline, XenoPort Inc. Horizant (gabapentin enacarbil) extended-release tablets for oral use: US prescribing information [online]. Available from URL: http://us.gsk.com/products/assets/us_horizant.pdf. Accessed 23 Aug 2012.
- 8.Lal R, Sukbuntherng J, Luo W, et al. Population pharmacokinetics and pharmacodynamics of gabapentin after administration of gabapentin enacarbil. J Clin Pharmacol. 2012. doi:10.1177/0091270012439209.
- 11.Cundy KC, Annamalai T, Bu L, et al. XP13512 [(±)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys. J Pharmacol Exp Ther. 2004;311(1):324–33.PubMedCrossRefGoogle Scholar
- 16.Lal R, Sukbuntherng J, Luo W, et al. Clinical pharmacokinetics of gabapentin after administration of gabapentin enacarbil extended-release tablets in patients with varying degrees of renal function using data from an open-label, single-dose pharmacokinetic study. Clin Ther. 2012;34(1):201–13.PubMedCrossRefGoogle Scholar
- 21.Bogan R, Ellenbogen AL, Becker PM, et al. Gabapentin enacarbil improves RLS symptoms and subjective measures of sleep in subjects with primary restless legs syndrome with and without severe sleep disturbance: secondary analyses from two studies [abstract no. P02.283]. In: 62nd Annual Meeting of the American Academy of Neurology; 2010 April 10–17; Toronto.Google Scholar
- 24.Lee D, Ziman R, Perkins A, et al. Gabapentin enacarbil improves pain associated with restless legs syndrome (RLS) [abstract no. 311]. J Pain. 2010;11(4 Suppl. 1):S53.Google Scholar
- 29.Astellas Pharma Inc., XenoPort Inc. Astellas and XenoPort announce the launch of Regnite® tablets for restless legs syndrome in Japan [online]. Available from URL: http://www.astellas.co/en/corporate/news/pdf/120709.eg.pdf Accessed 23 Aug 2012.
- 30.Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorders in adults: an update for 2012. Practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35(8):1039–62.PubMedGoogle Scholar
- 31.International Restless Legs Syndrome Study Group Task Force. Summary of recommendations for the long-term treatment of RLS/WED from an IRLSSG task force [online]. Available from URL: http://irlssg.org/wp-content/uploads/2012/07/Summary-of-RLS-treatment-recommendations-FINAL.pdf. Accessed 15 Oct 2012.