NCT01494532已完成4 期
A Fixed Dose, Dose-response Study of Ropinirole Prolonged Release (PR) as Adjunctive Treatment to L-dopa in Patients With Advanced Parkinson's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 352
- 试验地点
- 1
- 主要终点
- Change From Baseline (BL) in Total Awake Time Spent "Off" at Week 4 of Maintenance Period
研究概览
简要总结
This is a double blind, fixed dose, parallel group study to characterize the dose response of ropinirole PR as adjunctive therapy to L-dopa in patients with late stage Parkinson's disease. The primary endpoint of this study, mean change from baseline in total awake time spent "off' is the same endpoint as used in the ropinirole PR pivotal study for advanced Parkinson's disease patients. This study includes a wide range of ropinirole doses (4-24mg) with the 8mg, 12mg, and 16mg per day doses powered to detect a 1.7 hour difference in total awake time spent "off" compared with placebo. The dose of Ldopa will remain stable through the study, unless the subject experiences tolerability issues that require an L-dopa dose reduction. Up to three L-dopa dose reductions are allowed, making a total reduction of up to approximately 30%. Keeping the L-dopa dose constant where possible is important to avoid confounding the efficacy data. Clinical review of the primary and secondary endpoints will be performed in order to establish the lowest maximally effective therapeutic dose.
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 (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of idiopathic Parkinson's disease (according to modified Hoehn & Yahr criteria Stages II-IV) and demonstrating lack of control with L-dopa therapy (e.g.
- •end of dose akinesia, simple on/off fluctuations).
- •Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening.
- •A minimum of 3 hours awake "off-time" for each diary day recorded during the baseline period.
- •Men or non-pregnant/non-breast-feeding women of at least 30 years of age at screening. Women of child-bearing potential must be practicing a clinically accepted method of contraception during the study and for at least one month prior to randomization and one month following completion of the study. Acceptable contraceptive methods include abstinence, oral contraception, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, surgical sterilisation, male partner sterilization, intrauterine device [IUD], or double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository.
- •Provide written informed consent for this study.
- •Be willing and able to comply with study procedures, including diary card completion and follow-up clinic visits.
排除标准
- •Late stage advanced subjects demonstrating incapacitating peak dose or diphasic dyskinesia on their stable dose of L-dopa
- •Consumption of any dopamine agonist, including ropinirole, within four weeks of randomization in the study.
- •Subjects with severe, clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, would render the subject unsuitable for the study (e.g., psychiatric, haematological, renal, hepatic, endocrinology, neurological [other than Parkinson's disease], cardiovascular, or active malignancy [other than basal cell carcinoma]).
- •Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety.
- •Subjects with prior or current major psychosis (e.g., schizophrenia or psychotic depression) e.g. scoring 3 or 4 on UPDRS item 2 [thought disorder] or item 3 [depression].
- •Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 [mentation].
- •Subjects with severe dizziness or fainting due to postural hypotension on standing.
- •Subjects with a personal history of melanoma.
- •Subjects with clinically significant abnormalities in laboratory or ECG tests at Screening. If findings are outside the normal range and the subject is included, it must be documented by the investigator that the findings are not of clinical significance.
- •Subjects who are diagnosed with an impulse control disorder. The modified MIDI will be conducted at screening. Subjects who score positive for this screen must be referred to a specialist for diagnostic evaluation.
- •Subjects who have an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Subjects who have a history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
- •Current alcohol or drug dependence.
- •Definite or suspected personal or family history of clinically significant adverse reactions or hypersensitivity to ropinirole (or to drugs with a similar chemical structure) that would preclude long-term dosing with ropinirole.
- •Withdrawal, introduction, or change in dose of hormone replacement therapy and/or any drug known to substantially inhibit CYP1A2 (e.g. ciprofloxacine, fluvoxamine, cimetidine, ethinyloestradiol) or induce CYP1A2 (e.g. tobacco, omeprazole) within 7 days prior to enrolment (randomization). Subjects already on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to enrolment (randomization) through the end of the treatment period.
- •Women who are pregnant or breast-feeding.
- •Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period.
- •Women who are pregnant or breast-feeding.
- •Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period.
研究组 & 干预措施
ropinirole
Experimental
active treatment 4, 8, 12, 16, or 24mg/day
干预措施: ropinirole/L-dopa (Drug)
placebo
Placebo Comparator
placebo comparator 4, 8, 12, 16, or 24mg/day
干预措施: placebo/L-dopa (Drug)
结局指标
主要结局
Change From Baseline (BL) in Total Awake Time Spent "Off" at Week 4 of Maintenance Period
时间窗: Baseline and Week 4 of the Maintenance Period (Study Week 17)
"Off" time is defined as the state in which the participants(par) symptoms include lack of mobility(bradykinesia) with or without additional features such as tremor or rigidity. Par were asked to record awake time "off ", awake time "on", troublesome dyskinesias(TD) during awake time "on", or time asleep for 30 minute intervals in 24 hr diary cards for 2 days preceding visits. Total number of awake hrs spent "off" per 24-hr period was the average of the 2 diary cards of the sum of awake hours spent "off" in each 24-hr diary card. BL is the last non-missing assessment measured on or before the first dose, change from BL was calculated by subtracting the BL values from the MP Week 4 values. Mixed Model Repeated Measures (MMRM) model used BL total awake time 'Off', treatment, visit and treatment by visit
次要结局
- Change From Baseline in Absolute Awake Time Spent "on" Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Percent Change From Baseline in Awake Time Spent "on" Without TD at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Percent of a 24- Hour Day Spent "on" Without TD at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Percent Change From Baseline in Awake Time Spent "Off" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Percent Awake Time Spent "on" Without TD at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Percent of a 24-hour Day Spent "Off" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in UPDRS ADL Score With Participants in an "Off" State, at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period(Baseline (BL) and Week 4 of the Maintenance Period (Study Week 17))
- Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy(From start of study treatment until end of treatment (assessed up to 18 weeks))
- Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) "Off" Time at Week-4 of Maintenance Period(Week 4 of the Maintenance Period (Study Week 17))
- Percentage of Participants With a >=1 Hour Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Percentage of Participants With a >=2 Hours Reduction in Baseline "Off" Time at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an "on" State, at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period(Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in Absolute Awake Time Spent "on" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Percent Change From Baseline in Awake Time Spent "on" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Percent Awake Time Spent "Off" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Percent Awake Time Spent "on" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Percent of a 24-hour Day Spent "on" at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an "on" State, at Week 4 of the Maintenance Period(Baseline and Week 4 of the Maintenance Period (Study Week 17))
研究者
研究点 (1)
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