Open-Label Safety Study of ADS-5102 in PD Patients With LID

Summary

This is a 105-week open-label study to evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release formulation of amantadine, in Parkinson's Disease (PD) patients with Levodopa Induced Dyskinesia (LID).

Timeline

Start

2014-07

Primary completion

2018-02

Completion

2018-02

Publications

• Background Aoki FY, Sitar DS. Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet. 1988 Jan;14(1):35-51. doi: 10.2165/00003088-198814010-00003.
• Background Colosimo C, Martinez-Martin P, Fabbrini G, Hauser RA, Merello M, Miyasaki J, Poewe W, Sampaio C, Rascol O, Stebbins GT, Schrag A, Goetz CG. Task force report on scales to assess dyskinesia in Parkinson's disease: critique and recommendations. Mov Disord. 2010 Jul 15;25(9):1131-42. doi: 10.1002/mds.23072.
• Background da Silva-Junior FP, Braga-Neto P, Sueli Monte F, de Bruin VM. Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. Parkinsonism Relat Disord. 2005 Nov;11(7):449-52. doi: 10.1016/j.parkreldis.2005.05.008. Epub 2005 Sep 9.
• Background Dallos V, Heathfield K, Stone P, Allen FA. Use of amantadine in Parkinson's disease. Results of a double-blind trial. Br Med J. 1970 Oct 3;4(5726):24-6. doi: 10.1136/bmj.4.5726.24.
• Background Del Sorbo F, Albanese A. Levodopa-induced dyskinesias and their management. J Neurol. 2008 Aug;255 Suppl 4:32-41. doi: 10.1007/s00415-008-4006-5.
• Background Encarnacion EV, Hauser RA. Levodopa-induced dyskinesias in Parkinson's disease: etiology, impact on quality of life, and treatments. Eur Neurol. 2008;60(2):57-66. doi: 10.1159/000131893. Epub 2008 May 15.
• Background Factor SA, Molho ES. Transient benefit of amantadine in Parkinson's disease: the facts about the myth. Mov Disord. 1999 May;14(3):515-7. doi: 10.1002/1531-8257(199905)14:33.0.co;2-z. No abstract available.
• Background Goetz CG, Nutt JG, Stebbins GT. The Unified Dyskinesia Rating Scale: presentation and clinimetric profile. Mov Disord. 2008 Dec 15;23(16):2398-403. doi: 10.1002/mds.22341.
• Background Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.
• Background Goetz CG, Stebbins GT, Chung KA, Hauser RA, Miyasaki JM, Nicholas AP, Poewe W, Seppi K, Rascol O, Stacy MA, Nutt JG, Tanner CM, Urkowitz A, Jaglin JA, Ge S. Which dyskinesia scale best detects treatment response? Mov Disord. 2013 Mar;28(3):341-6. doi: 10.1002/mds.25321. Epub 2013 Feb 6.
• Background Hayden FG, Gwaltney JM Jr, Van de Castle RL, Adams KF, Giordani B. Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults. Antimicrob Agents Chemother. 1981 Feb;19(2):226-33. doi: 10.1128/AAC.19.2.226.
• Background Jackson G, Stanley E, Lee Muldoon R. Chemoprophylaxis of viral respiratory diseases. Bulletin Pan Am Health Org. 1967; 147: 595-603.
• Background Luginger E, Wenning GK, Bosch S, Poewe W. Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease. Mov Disord. 2000 Sep;15(5):873-8. doi: 10.1002/1531-8257(200009)15:53.0.co;2-i.
• Background Ory-Magne F, Corvol JC, Azulay JP, Bonnet AM, Brefel-Courbon C, Damier P, Dellapina E, Destee A, Durif F, Galitzky M, Lebouvier T, Meissner W, Thalamas C, Tison F, Salis A, Sommet A, Viallet F, Vidailhet M, Rascol O; NS-Park CIC Network. Withdrawing amantadine in dyskinetic patients with Parkinson disease: the AMANDYSK trial. Neurology. 2014 Jan 28;82(4):300-7. doi: 10.1212/WNL.0000000000000050. Epub 2013 Dec 26.
• Background Paci C, Thomas A, Onofrj M. Amantadine for dyskinesia in patients affected by severe Parkinson's disease. Neurol Sci. 2001 Feb;22(1):75-6. doi: 10.1007/s100720170054.
• Background Parkes JD, Zilkha KJ, Marsden P, Baxter RC, Knill-Jones RP. Amantadine dosage in treatment of Parkinson's disease. Lancet. 1970 May 30;1(7657):1130-3. doi: 10.1016/s0140-6736(70)91211-0. No abstract available.
• Background Sawada H, Oeda T, Kuno S, Nomoto M, Yamamoto K, Yamamoto M, Hisanaga K, Kawamura T; Amantadine Study Group. Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial. PLoS One. 2010 Dec 31;5(12):e15298. doi: 10.1371/journal.pone.0015298.
• Background Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study. Brain. 2000 Nov;123 ( Pt 11):2297-305. doi: 10.1093/brain/123.11.2297.
• Background Schwab RS, Poskanzer DC, England AC Jr, Young RR. Amantadine in Parkinson's disease. Review of more than two years' experience. JAMA. 1972 Nov 13;222(7):792-5. doi: 10.1001/jama.222.7.792. No abstract available.
• Background Snow BJ, Macdonald L, Mcauley D, Wallis W. The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study. Clin Neuropharmacol. 2000 Mar-Apr;23(2):82-5. doi: 10.1097/00002826-200003000-00004.
• Background Spencer TJ, Biederman J, Ciccone PE, Madras BK, Dougherty DD, Bonab AA, Livni E, Parasrampuria DA, Fischman AJ. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry. 2006 Mar;163(3):387-95. doi: 10.1176/appi.ajp.163.3.387.
• Background Swanson JM, Volkow ND. Pharmacokinetic and pharmacodynamic properties of stimulants: implications for the design of new treatments for ADHD. Behav Brain Res. 2002 Mar 10;130(1-2):73-8. doi: 10.1016/s0166-4328(01)00433-8.
• Background Thomas A, Iacono D, Luciano AL, Armellino K, Di Iorio A, Onofrj M. Duration of amantadine benefit on dyskinesia of severe Parkinson's disease. J Neurol Neurosurg Psychiatry. 2004 Jan;75(1):141-3.
• Background Tyrrell DA, Bynoe ML, Hoorn B. Studies on the antiviral activity of 1-adamantanamine. Br J Exp Pathol. 1965 Aug;46(4):370-5. No abstract available.
• Background Verhagen Metman L, Del Dotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease. Neurology. 1998 May;50(5):1323-6. doi: 10.1212/wnl.50.5.1323.
• Background Metman LV, Del Dotto P, LePoole K, Konitsiotis S, Fang J, Chase TN. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol. 1999 Nov;56(11):1383-6. doi: 10.1001/archneur.56.11.1383.
• Background Volkow ND, Wang GJ, Fowler JS, Gatley SJ, Logan J, Ding YS, Hitzemann R, Pappas N. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998 Oct;155(10):1325-31. doi: 10.1176/ajp.155.10.1325.
• Background Wolf E, Seppi K, Katzenschlager R, Hochschorner G, Ransmayr G, Schwingenschuh P, Ott E, Kloiber I, Haubenberger D, Auff E, Poewe W. Long-term antidyskinetic efficacy of amantadine in Parkinson's disease. Mov Disord. 2010 Jul 30;25(10):1357-63. doi: 10.1002/mds.23034.
• Background Wright Willis A, Evanoff BA, Lian M, Criswell SR, Racette BA. Geographic and ethnic variation in Parkinson disease: a population-based study of US Medicare beneficiaries. Neuroepidemiology. 2010;34(3):143-51. doi: 10.1159/000275491. Epub 2010 Jan 15.
• Hauser RA, Pahwa R, Tanner CM, Oertel W, Isaacson SH, Johnson R, Felt L, Stempien MJ. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson's Disease (EASE LID 2 Study): Interim Results of an Open-Label Safety Study. J Parkinsons Dis. 2017;7(3):511-522. doi: 10.3233/JPD-171134.

Drugs

Indications