A Study ROP116991, Clinical Evaluation of 18 to 24mg/Day Ropinirole CR for Parkinson's Disease.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at Week 12 in the CR High-dose Group
研究概览
简要总结
This study is a Phase III, multicentre, randomized, initial double-blind study with subsequent open label phases. The study will havea screening phase (4 weeks), a dose increase effect verification phase (12 weeks), a down titration 1 phase (1 week), a long-term phase (39 weeks), down titration 2 phase (1 to 2 weeks) and a follow up phase. Subjects will be assigned to Ropinirole CR high-dose group or Ropinirole CR maintenance group at a ratio of 3:1. This study is being conducted to evaluate the efficacy (effect of increasing Ropinirole dose from 16 mg/day to 18-24 mg/day) of the Ropinirole CR tablets in early and advanced PD patients who have not achieved an optimal therapeutic response with marketed Ropinirole Immediate release (IR) (15 mg/day) or marketed Ropinirole CR (16 mg/day) formulations.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria at the start of the screening
- •Patients who are diagnosed as Parkinson's Disease with severity of the modified Hoehn & Yahr criteria Stages I-IV.
- •Monotherapy subject: Subjects who have never received L-dopa, or subjects who have had prior exposure to L-dopa (up to 450 milligram (mg)/day) for up to 3 months in total and L-dopa treatment has been discontinued, for a minimum of 4 weeks prior to the screening phase. 2) L-dopa adjunct subject: Subjects receiving L-dopa (up to 450 mg/day) for at least 4 weeks prior to the screening phase.
- •Patients receiving 15mg/day Ropinirole IR or 16mg/day Ropinirole CR for 4 weeks prior to the screening phase, UPDRS Part III total (on) scores is 10 points or more at screening visit and can expect clinical efficacy by increasing Ropinirole CR.
- •Age: 20years or older (at the time of informed written consent)
- •Informed consent: Patients who are able to give informed written consent in person. (i.e. patients who are capable of giving informed written consent on their own)
- •Sex: Either sex. Women of child-bearing potential will be eligible for inclusion in this study. However they have to have a negative pregnancy test at the screening visit and will have to agree to further pregnancy testing at the time points determined in study assessments and procedures and practice one of the methods of contraception mentioned in the protocol from the screening visit until the end of the follow-up examination - Outpatient status
- •corrected QT (QTc) <450 millisecond (msec) or <480msec for subjects with Bundle Branch Block. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
- •Liver function tests: Patients with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2x upper limit of normal (ULN); and Alkaline Phosphatase and bilirubin =< 1.5xULN (isolated bilirubin > 1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) at the screening visit.
- •Randomization Criteria
- •Patients whose UPDRS Part III total (on) scores is 10 points or more at week 0
- •Patients who did not achieve an optimal therapeutic response by treatment with 16mg/day Ropinirole CR and required higher dose of Ropinirole CR
- •Patients who are 80% or more compliant taking study drug
- •Exclusion Criteria
- •Late stage advanced patients demonstrating incapacitating peak dose or biphasic dyskinsia on their stable dose of L-dopa.
- •Patients who have used any other dopamine agonist (except for Ropinirole IR and CR) within 4 weeks prior to the screening phase.
- •Patients who have been treated with the following drugs at 4 weeks or earlier before the start of the screening phase, and whose treatment regimen of the drug has been changed. Anticholinergic agents: trihexyphenidyl hydrochloride, piroheptine hydrochloride, mazaticol hydrochloride, metixene hydrochloride, biperiden hydrochloride, profenamine, amantadine hydrochloride,droxidopa, citicoline, selegiline hydrochloride, entacapone, zonisamide, Estrogens, CYP1A2 inhibitors.
- •Patients who have been changing in smoking habit (started or stopped smoking) within the screening phase.
- •Patients who have been treated with any other investigational drug within 12 weeks prior to the screening phase.
- •Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder).
- •Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).
- •Patients with a current or history of drug abuse or alcoholism.
- •Patients with severe dementia such as score 3 or 4 of the UPDRS item 1 (Mentation, behaviour, and mood).
- •Patients with current or history of major psychosis (e.g. schizophrenia or psychotic depression) such as score 3 or 4 of the UPDRS item 2 (thought disorder) or item 3(depression).
- •Patients who have received surgical treatment for PD in the past (e.g. pallidectomy, deep brain stimulation).
- •Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study or within 30 days after the last dose of the study drug.
- •Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulapathy, hypoalbuminaemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Chronic hepatitis B administered immunosuppressive agents due to risk of hapatitis B reactivation.
- •Patients with a history of drug allergy to Ropinirole hydrochloride.
- •Except for patients with a history of basal cell carcinoma, patients with a current or history of cancer or malignant tumor within 5 years prior to the screening phase.
- •Others whom the investigator (subinvestigator) considers ineligible for the study.
排除标准
- 未提供
研究组 & 干预措施
Ropinirole CR high-dose group
The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase, where Ropinirole CR dose will titrated (2 mg /day/week) from 18 mg/day up to a maximum 24mg/day at intervals of 1 week or longer for 8 weeks, till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg /day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.
干预措施: Ropinirole CR 2mg tablet (Drug)
Ropinirole CR high-dose group
The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase, where Ropinirole CR dose will titrated (2 mg /day/week) from 18 mg/day up to a maximum 24mg/day at intervals of 1 week or longer for 8 weeks, till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg /day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.
干预措施: Ropinirole CR 8mg tablet (Drug)
Ropinirole CR maintenance group
The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase and Ropinirole CR dose will maintained at 16mg/day and placebo will be increased at intervals of 1 week for 8 weeks till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg/day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.
干预措施: Ropinirole CR 2mg tablet (Drug)
Ropinirole CR maintenance group
The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase and Ropinirole CR dose will maintained at 16mg/day and placebo will be increased at intervals of 1 week for 8 weeks till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg/day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.
干预措施: Ropinirole CR 8mg tablet (Drug)
Ropinirole CR maintenance group
The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase and Ropinirole CR dose will maintained at 16mg/day and placebo will be increased at intervals of 1 week for 8 weeks till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg/day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.
干预措施: Ropinirole CR matching Placebo tablet (Drug)
结局指标
主要结局
Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at Week 12 in the CR High-dose Group
时间窗: Baseline and Week 12
The Japanese Unified Parkinson's Disease Rating Scale (UPDRS) assesses the status of Parkinson's Disease (PD) participants objectively. Part III assessed motor examination on 27 items. Participants received a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Baseline is defined as the value evaluated at Week 0. Mean change from Baseline was calculated as the total score at Week 12 minus the total score at Baseline. The analyses for the Dose Increase Effect Verification Phase was performed using the last observation carried forward (LOCF) data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit. The imputation was conducted using the data within only the Dose Increase Effect Verification Phase; therefore, the value observed in the Dose Increase Effect Verification Phase was not used to impute a missing data in the Long-term Phase.
次要结局
- Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Number of Participants Achieving a 30% and 20% Reduction From Baseline in the UPDRS Total Part 3 Score at the Indicated Visits in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Percent Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in Actual Hours of Awake Time Spent "On"Without Troublesome Dyskinesias at the Indicated Visits Only in Participants Who Received L-dopa Adjunct(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at the Indicated Visits(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long-term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in the Actual Hours of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Change From Baseline in the Percentage of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Change From Baseline in Actual Hours of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct(Baseline, Weeks, 2, 4, 6, 8 and 12)
- Mean Change From Baseline in UPDRS Part 3 Total Score at the Indicated Visits for Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49, 52)
- Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long-term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Percent Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Long-term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Number of Participants Achieving a 30% and 20% Reduction From Baseline in the UPDRS Total Part 3 Score at the Indicated Visits in Long Term Phase.(Baseline (Week 13), Weeks 17, 21, 25, 37, 49, 52)
- Change From Baseline in Percentage of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Number of Participants With an Improvement (Responder) in the Clinical Global Impression (CGI) Global Improvement Scale at Week 12(Week 12)
- Number of Participants Remaining in the Study(From the start of the study medication (Week 0) until Week 52)
- Change From Baseline in the Actual Hours of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in Actual Hours of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in Actual Hours of Awake Time Spent "On" Without Troublesome Dyskinesias at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in the Percentage of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)
- Change From Baseline in Percentage of Awake Time Spent "On" Without Troublesome Dyskinesias at the Indicated Visits Only in Participants Who Received L-dopa Adjunct in Long Term Phase(Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52)