Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease

Summary

The primary purpose of this study is to establish a dosage of isradipine CR that is tolerable and demonstrates preliminary efficacy for utilization in future pivotal efficacy studies.

Timeline

Start

2009-07

Primary completion

2011-12

Completion

2012-02

Publications

• Background Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993 Jan 21;328(3):176-83. doi: 10.1056/NEJM199301213280305.
• Background Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002 Apr 3;287(13):1653-61. doi: 10.1001/jama.287.13.1653.
• Background Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol. 2004 Apr;61(4):561-6. doi: 10.1001/archneur.61.4.561.
• Background NINDS NET-PD Investigators. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 2006 Mar 14;66(5):664-71. doi: 10.1212/01.wnl.0000201252.57661.e1. Epub 2006 Feb 15.
• Background NINDS NET-PD Investigators. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007 Jan 2;68(1):20-8. doi: 10.1212/01.wnl.0000250355.28474.8e.
• Background Becker C, Jick SS, Meier CR. Use of antihypertensives and the risk of Parkinson disease. Neurology. 2008 Apr 15;70(16 Pt 2):1438-44. doi: 10.1212/01.wnl.0000303818.38960.44. Epub 2008 Feb 6.
• Background Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004 Oct;318(1):121-34. doi: 10.1007/s00441-004-0956-9. Epub 2004 Aug 24.
• Background Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ. 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature. 2007 Jun 28;447(7148):1081-6. doi: 10.1038/nature05865. Epub 2007 Jun 10.
• Background Christensen HR, Antonsen K, Simonsen K, Lindekaer A, Bonde J, Angelo HR, Kampmann JP. Bioavailability and pharmacokinetics of isradipine after oral and intravenous administration: half-life shorter than expected? Pharmacol Toxicol. 2000 Apr;86(4):178-82. doi: 10.1034/j.1600-0773.2000.d01-32.x.
• Background de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 Jun;5(6):525-35. doi: 10.1016/S1474-4422(06)70471-9.
• Background Dodel RC, Singer M, Kohne-Volland R, Szucs T, Rathay B, Scholz E, Oertel WH. The economic impact of Parkinson's disease. An estimation based on a 3-month prospective analysis. Pharmacoeconomics. 1998 Sep;14(3):299-312. doi: 10.2165/00019053-199814030-00006.
• Background Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007 Jan 30;68(5):384-6. doi: 10.1212/01.wnl.0000247740.47667.03. Epub 2006 Nov 2.
• Background Elm JJ, Goetz CG, Ravina B, Shannon K, Wooten GF, Tanner CM, Palesch YY, Huang P, Guimaraes P, Kamp C, Tilley BC, Kieburtz K; NET-PD Investigators. A responsive outcome for Parkinson's disease neuroprotection futility studies. Ann Neurol. 2005 Feb;57(2):197-203. doi: 10.1002/ana.20361.
• Background Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K; Parkinson Study Group. Levodopa and the progression of Parkinson's disease. N Engl J Med. 2004 Dec 9;351(24):2498-508. doi: 10.1056/NEJMoa033447.
• Background Gill DJ, Freshman A, Blender JA, Ravina B. The Montreal cognitive assessment as a screening tool for cognitive impairment in Parkinson's disease. Mov Disord. 2008 May 15;23(7):1043-1046. doi: 10.1002/mds.22017.
• Background Goetz CG, LeWitt PA, Weidenman M. Standardized training tools for the UPDRS activities of daily living scale: newly available teaching program. Mov Disord. 2003 Dec;18(12):1455-8. doi: 10.1002/mds.10591.
• Background Goetz CG, Stebbins GT, Chmura TA, Fahn S, Klawans HL, Marsden CD. Teaching tape for the motor section of the unified Parkinson's disease rating scale. Mov Disord. 1995 May;10(3):263-6. doi: 10.1002/mds.870100305.
• Background Huse DM, Schulman K, Orsini L, Castelli-Haley J, Kennedy S, Lenhart G. Burden of illness in Parkinson's disease. Mov Disord. 2005 Nov;20(11):1449-54. doi: 10.1002/mds.20609.
• Background Jankovic J, Hunter C. A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson's disease. Parkinsonism Relat Disord. 2002 Mar;8(4):271-6. doi: 10.1016/s1353-8020(01)00040-2.
• Background Johnson BA, Javors MA, Lam YW, Wells LT, Tiouririne M, Roache JD, Ait-Daoud N, Lawson K. Kinetic and cardiovascular comparison of immediate-release isradipine and sustained-release isradipine among non-treatment-seeking, cocaine-dependent individuals. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):15-20. doi: 10.1016/j.pnpbp.2004.08.014. Epub 2004 Nov 11.
• Background Kupsch A, Sautter J, Schwarz J, Riederer P, Gerlach M, Oertel WH. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in non-human primates is antagonized by pretreatment with nimodipine at the nigral, but not at the striatal level. Brain Res. 1996 Nov 25;741(1-2):185-96. doi: 10.1016/s0006-8993(96)00917-1.
• Background Leentjens AF, Verhey FR, Luijckx GJ, Troost J. The validity of the Beck Depression Inventory as a screening and diagnostic instrument for depression in patients with Parkinson's disease. Mov Disord. 2000 Nov;15(6):1221-4. doi: 10.1002/1531-8257(200011)15:63.0.co;2-h.
• Background Levy G, Kaufmann P, Buchsbaum R, Montes J, Barsdorf A, Arbing R, Battista V, Zhou X, Mitsumoto H, Levin B, Thompson JL. A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS. Neurology. 2006 Mar 14;66(5):660-3. doi: 10.1212/01.wnl.0000201182.60750.66.
• Background Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
• Background Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology. 2001 Jun;56(11 Suppl 5):S1-S88. doi: 10.1212/wnl.56.suppl_5.s1. No abstract available.
• Background Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning and well being for individuals with Parkinson's disease. Qual Life Res. 1995 Jun;4(3):241-8. doi: 10.1007/BF02260863.
• Background Richards M, Marder K, Cote L, Mayeux R. Interrater reliability of the Unified Parkinson's Disease Rating Scale motor examination. Mov Disord. 1994 Jan;9(1):89-91. doi: 10.1002/mds.870090114.
• Background Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50. doi: 10.1001/archneur.59.10.1541.
• Background Simuni T, Borushko E, Avram MJ, Miskevics S, Martel A, Zadikoff C, Videnovic A, Weaver FM, Williams K, Surmeier DJ. Tolerability of isradipine in early Parkinson's disease: a pilot dose escalation study. Mov Disord. 2010 Dec 15;25(16):2863-6. doi: 10.1002/mds.23308.
• Background Striessnig J, Koschak A, Sinnegger-Brauns MJ, Hetzenauer A, Nguyen NK, Busquet P, Pelster G, Singewald N. Role of voltage-gated L-type Ca2+ channel isoforms for brain function. Biochem Soc Trans. 2006 Nov;34(Pt 5):903-9. doi: 10.1042/BST0340903.
• Background Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):976-82. doi: 10.1212/01.wnl.0000206363.57955.1b.
• Background Twelves D, Perkins KS, Counsell C. Systematic review of incidence studies of Parkinson's disease. Mov Disord. 2003 Jan;18(1):19-31. doi: 10.1002/mds.10305.
• Background Urien S, Pinquier JL, Paquette B, Chaumet-Riffaud P, Kiechel JR, Tillement JP. Effect of the binding of isradipine and darodipine to different plasma proteins on their transfer through the rat blood-brain barrier. Drug binding to lipoproteins does not limit the transfer of drug. J Pharmacol Exp Ther. 1987 Jul;242(1):349-53.
• Background Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ; REAL-PET Study Group. Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol. 2003 Jul;54(1):93-101. doi: 10.1002/ana.10609.
• Background Zadikoff C, Fox SH, Tang-Wai DF, Thomsen T, de Bie RM, Wadia P, Miyasaki J, Duff-Canning S, Lang AE, Marras C. A comparison of the mini mental state exam to the Montreal cognitive assessment in identifying cognitive deficits in Parkinson's disease. Mov Disord. 2008 Jan 30;23(2):297-9. doi: 10.1002/mds.21837.

Drugs

Indications