Efficacy and Safety of Amantadine Hydrogen Chloride (HCl) ER Tablets in Parkinson's Disease Subjects With LID
Condition: Parkinson's Disease; Levodopa Induced Dyskinesia (LID)
MeSH terms: Parkinson Disease; Dyskinesias
Intervention: amantadine HCl ER; Placebo
Intervention description: Subjects are given either 240 mg amantadine HCl ER tablet or 320 mg amantadine HCl ER tablet; subjects are given an identical placebo tablet
Intervention MeSH terms: Amantadine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 135.0
Sex: All
Minimum age: 30 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Parkinson's Disease; Levodopa Induced Dyskinesia (LID); LID; Parkinsonism; Dyskinesia

Summary:

      The purpose of this multi-center, randomized, double-blind, parallel-group, 26 week study is
      to compare the efficacy and safety of two different dose levels of Amantadine Extended
      Release Tablets to placebo for the treatment of levodopa induced dyskinesia in patients with
      Parkinson's disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed Institutional Review Board (IRB)/ Independent Ethics Committee (IEC) informed
             consent form.

          -  Idiopathic Parkinson's disease per the United Kingdom (UK) Parkinson's Disease Society
             Brain Bank criteria.

          -  Male or female 30 to 85 years old.

          -  Levodopa induced, predictable peak-effect dyskinesia considered problematic and/or
             disabling.

          -  Screening serum creatinine level within normal range

          -  On stable doses of all oral anti-Parkinson's medication, including any levodopa
             preparation, for 30 days and be willing to remain on the same doses throughout the
             trial.

          -  The subject/caregiver must demonstrate the ability to complete an accurate home diary
             based on training and evaluation during the screening period.

        Exclusion Criteria:

          -  Secondary parkinsonian syndrome, such as vascular, postinflammatory,drug-induced,
             neoplastic and post-traumatic parkinsonism or any atypical parkinsonian syndrome
             (e.g., Progressive Supranuclear Palsy, Multi-System Atrophy, etc.);

          -  Use of amantadine within 14 days before study start, or previously had an adverse
             event to amantadine

          -  Currently taking neuroleptics and atypical antipsychotic agents, acetylcholinesterase
             inhibitors, apomorphine, rimantadine, memantine and dextromethorphan and quinidine if
             used in combination for treating dyskinesia.

          -  History of neurosurgical intervention for treating Parkinson's s disease (i.e.
             pallidotomy or implanted with a deep brain stimulator)

          -  Any medical condition or past medical history that would increase the risk of exposure
             to Amantadine HCl Extended Release Tablets or interfere with safety and efficacy
             evaluations.

          -  History of cancer within 5 years of screening with following exceptions: adequately
             treated non-melanomatous skin cancers, localized bladder cancer, non-metastatic
             prostate cancer or in situ cervical cancer.

          -  History or current diagnosis of schizophrenia or bipolar disorder;

          -  Inadequately treated Major Depressive Disorder. Subjects on stable doses of selective
             serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors
             (SNRIs) are eligible for the study;

          -  Is at imminent risk of suicide or had a suicide attempt within 6 months of screening

          -  History or current diagnosis of Impulse Control Disorder

          -  Calculated plasma creatinine clearance of <60 mL/min at screening

          -  History of or currently has any of the following clinically significant conditions,
             cardiovascular, respiratory, renal, hepatic, or gastrointestinal disease

          -  Any clinically significant vital sign, ECG, or laboratory abnormalities;

          -  A positive test for HIV antibody or history of HIV; hepatitis B surface antigen unless
             the positive test followed a recent (<28 days) vaccination for hepatitis B; hepatitis
             C antibody;

          -  A positive urine drug test.

          -  Pregnant or breastfeeding at screening or has a positive pregnancy test

          -  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 the screening visit to at least 4 weeks after the completion of study treatment.

          -  History of alcohol or narcotic substance abuse ≤1 year before screening.

          -  Has dementia or another psychiatric illness that prevents provision of informed
             consent.

          -  Has a known hypersensitivity to the study treatment(s), based on known allergies to
             drugs of the same class including rimantadine HCl and memantine HCl.

          -  Has participated in other studies involving investigational drugs or surgeries within
             the last 30 days or investigational biologics within the last 6 months prior to
             screening.

          -  Plans to undergo major elective surgery during the course of the study.

          -  Received administration of Live Attenuated Influenza Vaccine (LAIV) within 2 weeks.

          -  Cognitive impairment, as evidenced by a score <26 on the Montreal Cognitive Assessment
             (MoCA) at the screening visit.