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

Parkinson's Disease (PD) Clinical Trial

Official title:

Open-Label Safety Study of ADS-5102 (Amantadine HCl) Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia (LID)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02202551
• Other study ID #: ADS-AMT-PD302
• Status: Completed
• Phase: Phase 3
• Start date: July 2014
• Est. completion date: February 2018

Study information

• Verified date: August 2020
• Source: Adamas Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

Participation in this study was offered to subjects who were described by one of the following 3 groups:

• Group 1: Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID and chose to immediately transition into the current study without a time gap; this group was subdivided into Group 1A, consisting of subjects who received ADS-5102 in the previous Adamas efficacy study, and Group 1P, consisting of subjects who received placebo in the previous Adamas efficacy study

• Group 2: Subjects who completed a previous Adamas efficacy study evaluating ADS-5102 in LID and entered the current study with a time gap

• Group 3: Subjects who would have been deemed ineligible for participation in a previous Adamas efficacy study due to having undergone DBS

Consented subjects who completed Screening (Visit 1) and met study eligibility criteria were to have a Baseline Visit and receive study drug. During Week 1, subjects took 170 mg of ADS-5102 (1 capsule) daily at bedtime. For Week 2, the dose was increased to 340 mg (2 capsules) daily at bedtime; this dose was to continue through Week 100. During the final week (Week 101) of the study, the ADS-5102 dose was reduced to 170 mg (1 capsule) daily at bedtime. Subjects were enrolled into the study at Visit 2 (Baseline/Week 0) and were to return to the clinic after 4, 8, 16, 28, 40, 52, 64, 76, 88, and 100 weeks of study drug dosing. Subjects were to receive a telephone reminder at the end of Week 1 to increase their dose during Week 2. At the Week 100 Visit, subjects were instructed to reduce their dose to 1 capsule daily at bedtime for 1 week. The amount of available, unused drug was assessed during the Week 100 Visit; subjects were given an additional bottle of study drug, if needed, to complete the 1 week of reduced dosing.

Efficacy, as measured with the MDS-UPDRS, was to be evaluated at all study visits, beginning with the Screening Visit, and excluding the Baseline and Week 4 Visits. A Safety Follow-up Visit was to occur approximately 2 weeks following the completion of treatment. AEs were recorded beginning with the first dose of study drug and continued through the Safety Follow-up Visit. Concomitant medications were recorded throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 85 Years

Eligibility

Inclusion Criteria:

• Signed a current IRB/REB/IEC-approved informed consent form

• Completed all study visits in previous Adamas efficacy study or were ineligible for participation in previous Adamas studies due to having undergone prior deep brain stimulation.

• Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria

• On a stable regimen of antiparkinson's medications at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily.

• History of peak dose dyskinesia that might benefit from specific dyskinesia treatment in the judgment of the subject and clinical investigator

Exclusion Criteria:

• Discontinued ADS-5102 in previous Adamas efficacy study due to intolerable or unacceptable AEs considered to be related to ADS-5102

• History of neurosurgical intervention related to Parkinson's disease, with the exception of deep brain stimulation

• History of seizures since completion of participation in previous Adamas studies or within 2 years

• History of stroke or TIA since completion of participation in previous Adamas studies or within 2 years

• History of cancer since completion of participation in previous Adamas studies or within 2 years, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer

• Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening

• If female is pregnant or lactating

• If a sexually active female, is not surgically sterile or at least 2 years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least 4 weeks after the completion of study treatment.

• Treatment with an investigational drug (other than ADS-5102) or device within 30 days prior to screening

• Treatment with an investigational biologic within 6 months prior to screening

• Current or planned participation in another interventional clinical trial

Related Conditions & MeSH terms

• Dyskinesia
• Dyskinesias
• Levodopa Induced Dyskinesia (LID)
• Parkinson Disease
• Parkinson's Disease (PD)

Intervention

Drug:
• ADS-5102

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Adamas Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Spain, 

References & Publications (29)

Aoki FY, Sitar DS. Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet. 1988 Jan;14(1):35-51. Review. — View Citation

Colosimo C, Martínez-Martín 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. Review. — View Citation

da Silva-Júnior 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. Epub 2005 Sep 9. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Jackson G, Stanley E, Lee Muldoon R. Chemoprophylaxis of viral respiratory diseases. Bulletin Pan Am Health Org. 1967; 147: 595-603.

Luginger E, Wenning GK, Bösch S, Poewe W. Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease. Mov Disord. 2000 Sep;15(5):873-8. — View Citation

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. — View Citation

Ory-Magne F, Corvol JC, Azulay JP, Bonnet AM, Brefel-Courbon C, Damier P, Dellapina E, Destée 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study. Brain. 2000 Nov;123 ( Pt 11):2297-305. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Tyrrell DA, Bynoe ML, Hoorn B. Studies on the antiviral activity of 1-adamantanamine. Br J Exp Pathol. 1965 Aug;46(4):370-5. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Reported AEs and Safety-Related Study Drug Discontinuations	The primary objective of the study was to evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release (ER) formulation of amantadine, administered at a dose of 340 mg once daily at bedtime for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD).	Up to 101 weeks
Secondary	Change From Baseline in Movement Disorder's Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Parts I-III Combined Scores)	To evaluate clinical progression of PD as assessed by the MDS-UPDRS, combined score, Parts I, II, and III.; Part I - non-motor experiences of daily living; Part II - motor experiences of daily living; Part III - motor examination. Parts I and II each contain 13 questions measured on a 5-point scale (0-4). Part III contains 18 objective rater assessments of the motor signs of PD measured on a 5-point scale (0-4).; Total range for combined score (Part I-III) is = 0-176. Generally for MDS-UPDRS scores and sub-scores, the lower the score, the better.; Parts I, II, and III are summed to make the total score.	Up to 101 weeks. MDS-UPDRS was performed at the following visits: Screening, Week 8, Week 16, Week 28, Week 40, Week 52, Week 64, Week 76, Week 88, Week 100 (or ET).
Secondary	Change From Baseline in Movement Disorder's Society - Unified Parkinson's Disease Rating Scale MDS-UPDRS (Part IV - Motor Complications)	This component (Questions 4.1 - 4.6) includes time spent with dyskinesia, functional impact of dyskinesia, time spent in OFF state, functional impact of fluctuations, complexity of motor fluctuations, painful OFF-state dystonia. Questions 4.1-4.6 are summed to make the Part IV score.; Generally for MDS-UPDRS scores and sub-scores, the lower the score, the better. Total range for Part IV is = 0-24	100 Weeks. MDS-UPDRS was performed at the following visits: Screening, Week 8, Week 16, Week 28, Week 40, Week 52, Week 64, Week 76, Week 88, Week 100 (or ET).