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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 87
- 主要终点
- Unified Dyskinesia Rating Scale
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
240mg Amantadine HCl ER tablets
Amantadine HCl ER Tablets 240mg daily for 12 weeks post two week titration phase.
干预措施: 240mg Amantadine HCl ER tablets (Drug)
320mg Amantadine HCl ER tablets
Amantadine HCl ER Tablets 320mg daily for 12 weeks post a two week dose titration phase.
干预措施: 320mg Amantadine HCl ER tablets (Drug)
Placebo tablets
Placebo Tablets matching Amantadine HCl ER Tablets taken daily for 16 weeks.
干预措施: Placebo tablets (Drug)
结局指标
主要结局
Unified Dyskinesia Rating Scale
时间窗: 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).
次要结局
- Mobility State Self-Assessment - Subject Diary Cards(Day 14 and Day 98 of treatment)