A Fixed Dose, Dose Response Study for Ropinirole Prolonged Release (PR) in Patients With Early Stage Parkinson's Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Change From Baseline (BL) in Unified Parkinson Disease (PD) Rating Scale (UPDRS) Motor Score
研究概览
简要总结
This study is a fixed dose, dose response study to characterize the dose response for ropinirole PR in early stage PD patients (Hoehn & Yahr stages I-III). After screening and baseline assessments, subjects will be randomized to one of six final target treatment groups (placebo, 2, 4, 8, 12 or 24mg/day ropinirole PR). The study will consist of a screening period, an up-titration period, a maintenance period, a down titration period and a follow up period. This study utilizes change from baseline in the UPDRS motor score as the primary endpoint, in line with that used in the ropinirole PR monotherapy pivotal study (SK&F101468/168). 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
- Single Group
- 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 I-III.)
- •Subjects aged 30 years or greater 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.
- •A baseline UPDRS motor score of at least
- •Limited prior exposure to low or moderate doses of L-DOPA (up to 3 months in total) or dopamine agonists including ropinirole (up to 6 months in total) is allowed provided treatment is discontinued for a minimum of 4 weeks prior to screening.
- •Provide written informed consent for this study.
- •Be willing and able to comply with study procedures.
排除标准
- •Subjects with Parkinson's disease in whom dopaminergic therapy is not warranted at the time of screening.
- •Subjects with severe, clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, 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 precluding 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 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 prior to enrolling (screening) in the study.
- •Subjects with an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Subjects with 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 baseline (randomization).
- •Subjects on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to baseline (randomization) through the end of the treatment period. Smokers should maintain normal smoking habit.
- •Women who are pregnant or breast-feeding.
- •Use of an investigational drug from 30 days or 5 half-lives (which ever is longer) prior to baseline (randomization) to the end of the treatment period.
研究组 & 干预措施
ropinirole
ropinirole 2, 4, 8, 12, or 24 mg/day
干预措施: ropinirole monotherapy (Drug)
placebo
placebo comparator 2, 4, 8, 12, or 24 mg/day
干预措施: ropinirole monotherapy (Drug)
placebo
placebo comparator 2, 4, 8, 12, or 24 mg/day
干预措施: placebo monotherapy (Drug)
结局指标
主要结局
Change From Baseline (BL) in Unified Parkinson Disease (PD) Rating Scale (UPDRS) Motor Score
时间窗: Baseline and Week 4 of the Maintenance Period (Study Week 17)
The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. One of the six features include the Part III - Motor Examination where scores can range 0-108 where the maximum score indicates the worse condition. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the individual post-randomization values. The least squares(LS) means were estimated using the mixed model repeated measures(MMRM) adjusting for BL UPDRS motor score and race(white versus other) or by using the non-parametric rank analysis of covariance(ANCOVA).
次要结局
- Number of Participants With a >=5 Points Reduction From Baseline in UPDRS Motor Score(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Number of Participants With a >=10 Points Reduction From Baseline in UPDRS Motor Score(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in UPDRS Activities of Daily Living(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy(Up to Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the UPDRS Part I (Mentation)(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in the Total UPDRS Score (Parts I-III)(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Number of Participants With a >=10 Points Reduction From Baseline in UPDRS Parts II and III Combined(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Responder Rate Defined as Participants With a >=30% Reduction in Baseline UPDRS Motor Score(Baseline and Week 4 of the Maintenance Period (Study Week 17))
- Responder Rate According to the Clinical Global Impression - Global Improvement (CGI-I) Scale(Week 4 of the Maintenance Period (Study Week 17))
- Change From Baseline in UPDRS Parts II and III Combined(Baseline and Week 4 of the Maintenance Period (Study Week 17))