Gabapentin Enacarbil: in Patients with Restless Legs Syndrome

Overview

Journal CNS Drugs

Specialties Neurology
Pharmacology

Date 2012 Nov 27

PMID 23179641

Citations 2

Authors

Lesley J Scott

Affiliations

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Abstract

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.

Citing Articles

Gabapentin Enacarbil: A Review in Restless Legs Syndrome.

Kim E, Deeks E Drugs. 2016; 76(8):879-87.

PMID: 27146056 DOI: 10.1007/s40265-016-0584-1.

Demographic and clinical characteristics of patients with restless legs syndrome in spine clinic.

Yang J, Cho Y, Kang S, Choi H J Korean Neurosurg Soc. 2014; 55(2):83-8.

PMID: 24653801 PMC: 3958578. DOI: 10.3340/jkns.2014.55.2.83.

References

Vignatelli L, Billiard M, Clarenbach P, Garcia-Borreguero D, Kaynak D, Liesiene V . EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep. Eur J Neurol. 2006; 13(10):1049-65. DOI: 10.1111/j.1468-1331.2006.01410.x. View

Bogan R, Cramer Bornemann M, Kushida C, Tran P, Barrett R . Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. Mayo Clin Proc. 2010; 85(6):512-21. PMC: 2878254. DOI: 10.4065/mcp.2009.0700. View

Winkelman J, Bogan R, Schmidt M, Hudson J, Derossett S, Hill-Zabala C . Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome. Mov Disord. 2011; 26(11):2065-72. DOI: 10.1002/mds.23771. View

Chen D, Lal R, Zomorodi K, Atluri H, Ho J, Luo W . Evaluation of gabapentin enacarbil on cardiac repolarization: a randomized, double-blind, placebo- and active-controlled, crossover thorough QT/QTc study in healthy adults. Clin Ther. 2012; 34(2):351-362.e3. DOI: 10.1016/j.clinthera.2012.01.002. View

Lal R, Sukbuntherng J, Luo W, Chen D, Vu A, Tovera J . Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers. Clin Ther. 2009; 31(8):1776-86. DOI: 10.1016/j.clinthera.2009.07.026. View

Aurora R, Kristo D, Bista S, Rowley J, Zak R, Casey K . The treatment of restless legs syndrome and periodic limb movement disorder 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.... Sleep. 2012; 35(8):1039-62. PMC: 3397811. DOI: 10.5665/sleep.1988. View

Lal R, Ellenbogen A, Chen D, Zomorodi K, Atluri H, Luo W . A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome. Clin Neuropharmacol. 2012; 35(4):165-73. DOI: 10.1097/WNF.0b013e318259eac8. View

Lee D, Ziman R, Perkins A, Poceta J, Walters A, Barrett R . A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. J Clin Sleep Med. 2011; 7(3):282-92. PMC: 3113968. DOI: 10.5664/JCSM.1074. View

Cundy K, Sastry S, Luo W, Zou J, Moors T, Canafax D . Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol. 2008; 48(12):1378-88. DOI: 10.1177/0091270008322909. View

10.

Cundy K, Annamalai T, Bu L, De Vera J, Estrela J, Luo W . 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. DOI: 10.1124/jpet.104.067959. View

11.

Cundy K, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K . XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters. J Pharmacol Exp Ther. 2004; 311(1):315-23. DOI: 10.1124/jpet.104.067934. View

12.

Lal R, Sukbuntherng J, Luo W, Chen D, Blumenthal R, Ho J . 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. 2011; 34(1):201-13. DOI: 10.1016/j.clinthera.2011.12.004. View

13.

Lal R, Sukbuntherng J, Ho J, Cundy K . A phase I, single-dose study of the disposition of 14C-radiolabeled gabapentin enacarbil in healthy male volunteers. Int J Clin Pharmacol Ther. 2011; 49(2):109-15. DOI: 10.5414/cpp49109. View

14.

VanMeter S, Kavanagh S, Warren S, Barrett R . Dose response of Gabapentin Enacarbil versus placebo in subjects with moderate-to-severe primary restless legs syndrome: an integrated analysis of three 12-week studies. CNS Drugs. 2012; 26(9):773-80. DOI: 10.2165/11634870-000000000-00000. View

15.

Inoue Y, Uchimura N, Kuroda K, Hirata K, Hattori N . Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 36(2):251-7. DOI: 10.1016/j.pnpbp.2011.10.009. View

16.

Yaltho T, Ondo W . The use of gabapentin enacarbil in the treatment of restless legs syndrome. Ther Adv Neurol Disord. 2010; 3(5):269-75. PMC: 3002665. DOI: 10.1177/1756285610378059. View

17.

Kushida C, Becker P, Ellenbogen A, Canafax D, Barrett R . Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology. 2009; 72(5):439-46. DOI: 10.1212/01.wnl.0000341770.91926.cc. View

18.

Ellenbogen A, Thein S, Winslow D, Becker P, Tolson J, Lassauzet M . A 52-week study of gabapentin enacarbil in restless legs syndrome. Clin Neuropharmacol. 2011; 34(1):8-16. DOI: 10.1097/WNF.0b013e3182087d48. View

19.

Satija P, Ondo W . Restless legs syndrome: pathophysiology, diagnosis and treatment. CNS Drugs. 2008; 22(6):497-518. DOI: 10.2165/00023210-200822060-00004. View

20.

Canafax D, Bhanegaonkar A, Bharmal M, Calloway M . Validation of the post sleep questionnaire for assessing subjects with restless legs syndrome: results from two double-blind, multicenter, placebo-controlled clinical trials. BMC Neurol. 2011; 11:48. PMC: 3120662. DOI: 10.1186/1471-2377-11-48. View