Double-blind, Placebo-controlled, Randomized, Multicentre Phase II/III Study to Evaluate the Efficacy and Safety of Lisuride, Applied Subcutaneously by Means of a Minipump in Patients With Advanced Parkinson's Disease Refractory to Conventional Oral Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change from baseline B0 to T6 in total daily "OFF-time and ON-time with troublesome dyskinesia
研究概览
简要总结
The aim of the study is to evaluate the long-term efficacy, local tolerability and safety of Lisuride applied as subcutaneous infusion compared to placebo in patients with advanced Parkinson's disease with motor fluctuations and "OFF" periods refractory to conventional treatment.
详细描述
The current CALIPSO study investigates the efficacy of a continuous lisuride infusion against the optimized previous oral therapy in patients experiencing motor fluctuations with OFF periods and/or strenuous dyskinesias of more than four hours per day.
The controlled core study is scheduled to last six weeks. Within the study the previous oral therapy will either be continued in a capsule/blinded design (while a placebo infusion is going on concurrently) or the oral therapy is substituted by lisuride infusion (while placebo capsules are administered at the same time).
After the controlled core study all patients whose condition has not worsened during the study (meaning those patients of the placebo infusion group as well, who were treated during the core study just as they were before), will be given the chance to continue with the infusion therapy with lisuride in an open extension phase.
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
- Double
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic Parkinson's disease for at least 3 years (diagnosis based on the UK Brain Bank Criteria)
- •Presence of motor fluctuations (wearing-off or other "OFF" periods) and / or presence of troublesome dyskinesia, with a total daily minimum of at least 4 hours, despite optimized oral anti-parkinsonian therapy
- •Stable levodopa intake, i.e. at least four doses of levodopa per day
- •Stable dosing of all other anti-parkinsonian drugs, such as dopamine agonists, COMT- and MAO-B inhibitors, amantadine, or anticholin-ergics for a minimum of four weeks prior to inclusion.
- •The following oral dopamine agonist drugs are allowed in this trial: pramipexol up to a total daily dose of 3,15mg, ropinirol up to a total daily dose of 24mg, cabergoline up to a total daily dose of 6mg or combinations Concomitant diseases are stable and well controlled Willingness and ability to comply with all trial requirements Written informed consent
排除标准
- •Non-idiopathic Parkinson's disease (e.g. drug-induced or other forms of secondary or atypical parkinsonism such as MSA)
- •Significant neurological symptoms not accounted for by Parkinson's disease
- •History or presence of dementia demonstrated by the Mini-mental status examination (MMSE < 24)
- •Presence of major depression according to DSM IV criteria (≥ 6 months)
- •History or presence of epilepsy
- •Presence of dopaminergic psychosis
- •Unstable severe concomitant diseases (e.g. liver diseases, kidney diseases or clinically relevant cardiac or coronary dysfunction)
- •Presence of heart valvular fibrosis or indication of significant valvular stenosis / insufficiency on echocardiogram
- •History of syncope and/or severe or otherwise symptomatic orthostatic hypotension
- •Present treatment with neuroleptics, including atypical neuroleptics
- •Treatment with other CNS active drug therapy (e.g. sedatives, hypnotics, anti-depressants, anxiolytics) unless the dose has been stable for at least four weeks prior to the baseline visit
- •Participation in another trial of an investigational drug within the last 28 days or current participation in another trial of an investigational drug
- •Clinically significant laboratory abnormalities
- •Previous neurosurgery for Parkinson's disease
- •Alcohol or drug abuse in the past three years
结局指标
主要结局
Change from baseline B0 to T6 in total daily "OFF-time and ON-time with troublesome dyskinesia
次要结局
- Secondary objectives are to evaluate quality of life, quality of sleep, UPDRS Score
- clinical global impression, safety and tolerability.
- After the double-blind period, long-term efficacy of lisuride will be assessed for further 2 years in an open-label extension of the study