Extended Release Amantadine Safety and Efficacy Study in Levodopa-Induced Dyskinesia (EASED Study)

• Total Objective Score (III, IV) of the UDysRS [ Time Frame: Baseline (Day 1) to week 8 ] [ Designated as safety issue: No ]
• ON time without troublesome dyskinesia (ON without dyskinesia plus ON with non-troublesome dyskinesia), based on a standardized PD home diary [ Time Frame: Baseline (Day 1) to week 8 ] [ Designated as safety issue: No ]
• Unified Parkinson's Disease Rating Scale (MDS-UPDRS), individual and combined scores (Parts I, II, III) [ Time Frame: Baseline (Day 1) to week 8 ] [ Designated as safety issue: No ]
• Clinician's Global Impression of Change in overall PD symptoms [ Time Frame: Baseline (Day 1) to week 8 ] [ Designated as safety issue: No ]
• Fatigue Severity Score (FSS) [ Time Frame: Baseline (Day 1) to week 8 ] [ Designated as safety issue: No ]

This is a multi-center, randomized, double-blind, placebo-controlled, 4-arm parallel group study to evaluate the tolerability and efficacy of each of three dose levels of ADS-5102 oral capsules, an extended release formulation of amantadine, dosed once daily for the treatment of levodopa-induced dyskinesia (LID) in subjects with Parkinson's disease (PD). The novel pharmacokinetic profile of ADS-5102 is expected to achieve i) higher amantadine plasma concentrations during daytime hours when dyskinesia as well as motor and non-motor symptoms of PD are most problematic, ii) low amantadine plasma concentrations overnight, which may reduce the sleep disturbances and vivid dreams occasionally associated with amantadine, and iii) a reduced initial rate of rise in plasma concentration, which is expected to improve overall tolerability of amantadine.

• Dyskinesia
• Levodopa Induced Dyskinesia
• Parkinson's Disease

• Placebo Comparator: Treatment A
  Intervention: Drug: ADS-5102 (extended release amantadine HCl)
• Active Comparator: Treatment B
  Low dose ADS-5102 (amantadine extended release)
  Intervention: Drug: ADS-5102 (extended release amantadine HCl)
• Active Comparator: Treatment C
  A mid-dose ADS-5102 (amantadine extended release)
  Intervention: Drug: ADS-5102 (extended release amantadine HCl)
• Active Comparator: Treatment D
  High dose ADS-5102 (amantadine extended release)
  Intervention: Drug: ADS-5102 (extended release amantadine HCl)

Inclusion Criteria:

• Signed a current IRB/IEC-approved informed consent form
• Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria
• On a stable regimen of antiparkinson's medications , including any levodopa preparation administered not less than three times daily, and willing to continue the same doses and regimens during study participation
• Experiencing troublesome dyskinesia following levodopa dosing (peak dose dyskinesia)
• Able to understand and complete a standardized PD home diary, following training

Exclusion Criteria:

• History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation)
• History of seizures or stroke/TIA within 2 years of screening
• History of cancer within 5 years of screening, except adequately treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic prostate cancer or in situ cervical cancer
• Estimated GFR < 50 mL/min/1.73m2
• 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, or has a positive pregnancy test result pre-dose
• 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 or device within 30 days prior to screening
• Treatment with an investigational biologic within 6 months prior to screening