Adenosine A 2A receptor antagonist istradefylline reduces daily OFF time in Parkinson's disease

Abstract

Background We evaluated the efficacy and safety of istradefylline, a selective adenosine A 2A receptor antagonist administered as adjunctive treatment to levodopa for 12 weeks in a double‐blind manner in Parkinson's disease patients with motor complications in Japan. Methods A total of 373 subjects were randomized to receive placebo (n = 126), istradefylline 20 mg/day (n = 123), or istradefylline 40 mg/day (n = 124). The primary efficacy variable was the change in daily OFF time. Other secondary variables were also evaluated. Results The change in daily OFF time was significantly reduced in the istradefylline 20 mg/day (−0.99 hours, P = .003) and istradefylline 40 mg/day (−0.96 hours, P = .003) groups compared with the placebo group (−0.23 hours). The most common adverse event was dyskinesia (placebo, 4.0%; istradefylline 20 mg/day, 13.0%; istradefylline 40 mg/day, 12.1%). Conclusions Istradefylline reduced daily OFF time and was well tolerated in Japanese PD patients with motor complications on levodopa treatment. © 2013 Movement Disorder Society

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References 19

1. 1.

   Rajput AH, Fenton ME, Birdi S, et al. Clinical-pathological study of levodopa complications. Mov Disord. 2002;17:289-296.

   Not in our library10.1002/mds.10031

2. 2.

   Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001;56:S1-S88.

   Not in our library10.1212/wnl.56.suppl_5.s1

3. 3.

   Mori A, Shindou T. Modulation of GABAergic transmission in the striatopallidal system by adenosine A2a receptors: a potential mechanism for the antiparkinsonian effects of A2A antagonists. Neurology. 2003;61:S44-S48.

   Not in our library10.1212/01.wnl.0000095211.71092.a0

4. 4.

   Jenner P. Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson’s disease. Expert Opin Investig Drugs. 2005;14:729-738.

   Not in our library10.1517/13543784.14.6.729

5. 5.

   Park A, Stacy M. Istradefylline for the treatment of Parkinson’s disease. Expert Opin Pharmacother. 2012;13:111-114.

   Not in our library10.1517/14656566.2012.643869

6. 6.

   Shiozaki S, Ichikawa S, Nakamura J, Kitamura S, Yamada K, Kuwana Y. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology. 1999;147:90-95.

   Not in our library10.1007/s002130051146

7. 7.

   Kanda T, Jackson MJ, Smith LA, et al. Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol. 1998;43:507-513.

   Not in our library10.1002/ana.410430415

8. 8.

   Grondin R, Bedard PJ, Hadj Tahar A, Gregoire L, Mori A, Kase H. Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology. 1999;52:1673-1677.

   Not in our library10.1212/wnl.52.8.1673

9. 9.

   Kanda T, Jackson MJ, Smith LA, et al. Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp Neurol. 2000;162:321-327.

   Not in our library10.1006/exnr.2000.7350

10. 10.

    Hauser RA, Hubble JP, Truong DD. Istradefylline US-001 Study Group. Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology. 2003;61:297-303.

    Not in our library10.1212/01.wnl.0000081227.84197.0b

11. 11.

    Bara-Jimenez W, Sherzai A, Dimitrova T, et al. Adenosine A2A receptor antagonist treatment of Parkinson’s disease. Neurology. 2003;61:293-296.

    Not in our library10.1212/01.wnl.0000073136.00548.d4

12. 12.

    LeWitt PA, Guttman M, Tetrud JW, et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol. 2008;63:295-302.

    Not in our library10.1002/ana.21315

13. 13.

    Stacy M, Silver D, Mendis T, et al. A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease. Neurology. 2008;70:2233-2240.

    Not in our library10.1212/01.wnl.0000313834.22171.17

14. 14.

    Hauser RA, Shulman LM, Trugman JM, et al. Study of istradefylline in patients with Parkinson’s disease on levodopa with motor fluctuations. Mov Disord. 2008;23:2177-2185.

    Not in our library10.1002/mds.22095

15. 15.

    Pourcher E, Fernandez HH, Stacy M, Mori A, Ballerini R, Chaikin P. Istradefylline for Parkinson’s disease patients experiencing motor fluctuations: results of the KW-6002-US-018 study. Parkinsonism Relat Disord. 2012;18:178-184.

    Not in our library10.1016/j.parkreldis.2011.09.023

16. 16.

    Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M. Japanese Istradefylline Study Group. Clinical efficacy of istradefylline (KW-6002) in Parkinson’s disease: a randomized, controlled study. Mov Disord. 2010;25:1437-1443.

    Not in our library10.1002/mds.23107

17. 17.

    Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55:181-184.

    Not in our library10.1136/jnnp.55.3.181

18. 18.

    Ochi M, Koga K, Kurokawa M, Kase H, Nakamura J, Kuwana Y. Systemic administration of adenosine A(2A) receptor antagonist reverses increased GABA release in the globus pallidus of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study. Neuroscience. 2000;100:53-62.

    Not in our library10.1016/s0306-4522(00)00250-5

19. 19.

    Brooks DJ, Doder M, Osman S, et al. Positron emission tomography analysis of [11C]KW-6002 binding to human and rat adenosine A2A receptors in the brain. Synapse. 2008;62:671-681.

    Not in our library10.1002/syn.20539

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