A Multicenter, Randomized, Placebo-controlled, Double-blind, 16 Week Study to Evaluate the Efficacy and Safety of Amantadine HCl Extended Release Tablets in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesias
Overview
- Phase
- Phase 3
- Intervention
- 240mg Amantadine HCl ER tablets
- Conditions
- Parkinson's Disease
- Sponsor
- Adamas Pharmaceuticals, Inc.
- Enrollment
- 87
- Primary Endpoint
- Unified Dyskinesia Rating Scale
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This study was terminated early due to slow enrollment with 87 of 162 planned subjects enrolled. The purpose of this multi-center, randomized, double-blind, parallel-group, 16 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.
Detailed Description
This study was terminated early due to slow enrollment with 87 of 162 planned subjects enrolled. Amantadine 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, 16 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed Investigational Review Board/Independent Ethics Review Committee (IRB/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
Arms & Interventions
240mg Amantadine HCl ER tablets
Amantadine HCl ER Tablets 240mg daily for 12 weeks post two week titration phase.
Intervention: 240mg Amantadine HCl ER tablets
320mg Amantadine HCl ER tablets
Amantadine HCl ER Tablets 320mg daily for 12 weeks post a two week dose titration phase.
Intervention: 320mg Amantadine HCl ER tablets
Placebo tablets
Placebo Tablets matching Amantadine HCl ER Tablets taken daily for 16 weeks.
Intervention: Placebo tablets
Outcomes
Primary Outcomes
Unified Dyskinesia Rating Scale
Time Frame: From baseline to Day 98
The Unified Dyskinesia Rating Scale is a validated tool for assessment of dyskinesia (involuntary movements) in Parkinson's Disease patients. Rating consists of the change from baseline to Day 98 of the sum of the 26 questions comprising the questionnaire. Each question in the questionnaire is rated on a 5 point scale from 0-4 where 0 is a better outcome. Questions assess: over the past week total hours with dyskinesia and total hours without dyskinesia; problems with speech, chewing and swallowing, eating, dressing, hygiene, handwriting, hobbies, balance, socializing, emotions, spasm or cramps, pain without dystonia (spasm or cramps) and pain from dystonia, the degree of impairment for each of 7 body parts, and the degree of disability in communication, drinking from a cup, dressing and ambulation. The minimum score is 0 (better) and the maximum score is 130 (worse).
Secondary Outcomes
- Mobility State Self-Assessment - Subject Diary Cards(Day 14 and Day 98 of treatment)