Efficacy and Safety of Amantadine Hydrogen Chloride (HCl) ER Tablets in Parkinson's Disease Subjects With LID

This study was terminated early due to slow enrollment with 135 of 162 planned subjects
enrolled. Amantadine HCl ER has been used for many years as a treatment for Parkinson's
disease. It has been reported in the literature to effectively treat the motor complications
of levodopa, especially dyskinesia, but it must be given 2 to 4 times a day. 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. The dose will be given once a day in the morning so that amantadine concentrations
are maintained throughout the day for treating the levodopa induced dyskinesia, but will be
lower during the night, potentially reducing the negative impact of amantadine on sleep.

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.