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A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.

Primary Purpose

Parkinson Disease

Status

Terminated

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

Ropinirole CR 2mg tablet

Ropinirole CR 8mg tablet

Ropinirole CR matching Placebo tablet

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Ropinirole, Parkinson's disease

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
1) 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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Ropinirole CR high-dose group

Ropinirole CR maintenance group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at Week 12 in the CR High-dose Group

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.

Secondary Outcome Measures

Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at the Indicated Visits

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

The Japanese 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. Number of participants achieving a 30% or greater and 20% or greater reduction from Baseline in UPDRS total part III score at Weeks 2, 4, 6, 8, and 12 are presented using 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.

Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

The Japanese UPDRS assesses the status of PD participants objectively. Part I evaluated mentation, behavior, and mood on 4 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 16. A higher score indicates more severe PD symptoms. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 0. The analyses for the Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at the planned visit.

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

The Japanese UPDRS assesses the status of PD participants objectively. Part 2 evaluated activities of daily living on 13 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 52. A higher score indicates more severe PD symptoms. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 0. The analyses for the Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "On" state is defined as the state at which PD symptoms are well controlled by the drug. The score of UPDRS part 2 in off status is rated as '0' (Normal/None), if L-dopa adjunct participants do not have diurnal fluctuations.

Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part 4 evaluated complications on 11 items, response for 4 items were scored numerically from 0-4 and response for other 7 items were Yes/No questions and responses are numerically scored as 0 for "No" and 1 for "Yes". The total score for the 11 items ranged from 0 to 23. A higher score indicates more severe PD symptoms. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 0. The analyses for the Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part I evaluated mentation, behavior, and mood on 4 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 16. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

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

The Japanese UPDRS assesses the status of PD participants objectively. Part 2 evaluates activities of daily living on 13 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 52. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "On" state is defined as the state at which PD symptoms are well controlled by the drug. The score of UPDRS part 2 in off status is rated as '0' (Normal/None), if L-dopa adjunct participants do not have diurnal fluctuations.

Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part 3 evaluated motor examination on 27 items, response for each items were scored numerically from 0-4. The total score for the 27 items ranged from 0 to 108. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part 4 evaluated complications on 11 items, response for 4 items were scored numerically from 0-4 and response for other 7 items were Yes/No questions and responses are numerically scored as 0 for "No" and 1 for "Yes". The total score for the 11 items ranged from 0 to 23. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long-term Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part I evaluated mentation, behavior, and mood on 4 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 16. A higher score indicates more severe PD symptoms.Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data. Full Analysis Set 2 (FAS2) Population comprised of all participants in the FAS1 and shifted to Long-term Phase, excluding those participants who received no dose of study medication and participants without UPDRS part III total score data after supply of the investigational product.

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

The Japanese UPDRS assesses the status of PD participants objectively. Part 2 evaluates activities of daily living on 13 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 52. A higher score indicates more severe PD symptoms.Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value at Week 13. If the value at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data."Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "On" state is defined as the state at which PD symptoms are well controlled by the drug. The score of UPDRS part 2 in off status is rated as '0' (Normal/None), if L-dopa adjunct participants do not have diurnal fluctuations.

Mean Change From Baseline in UPDRS Part 3 Total Score at the Indicated Visits for Long Term Phase

The Japanese UPDRS assesses the status of PD participants objectively. Part 3 evaluates motor examination on 27 items, response for each items were scored numerically from 0-4. The total score for the 27 items ranged from 0 to 108. A higher score indicates more severe PD symptoms. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long Term Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part 4 evaluated complications on 11 items, response for 4 items were scored numerically from 0-4 and response for other 7 items were Yes/No questions and responses are numerically scored as 0 for "No" and 1 for "Yes". The total score for the 11 items ranged from 0 to 23. A higher score indicates more severe PD symptoms.Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long Term Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part I evaluated mentation, behavior, and mood on 4 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 16. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

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

The Japanese UPDRS assesses the status of PD participants objectively. Part 2 evaluates activities of daily living on 13 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 52. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value at Week 13. If the value at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data."Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "On" state is defined as the state at which PD symptoms are well controlled by the drug. The score of UPDRS part 2 in off status is rated as '0' (Normal/None), if L-dopa adjunct participants do not have diurnal fluctuations.

Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Long Term Phase

The Japanese UPDRS assessed the status of PD participants objectively. Part 3 evaluated motor examination on 27 items, response for each items were scored numerically from 0-4. The total score for the 27 items ranged from 0 to 108. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long-term Phase

The Japanese UPDRS assesses the status of PD participants objectively. Part 4 evaluates complications on 11 items, response for 4 items were scored numerically from 0-4 and response for other 7 items were Yes/No questions and responses are numerically scored as 0 for "No" and 1 for "Yes". The total score for the 11 items ranged from 0 to 23. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Change From Baseline in the Actual Hours of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline in awake time spent "Off"(actual hours) is calculated as awake time spent "Off" (hours) at the indicated visit minus awake time spent "Off" (hours) at Baseline. Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Change From Baseline in the Percentage of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Percentage of awake time spent "off" is defined as sum of two days off time (hours) divided by sum of two days awake time (hours) and multiplied by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "off") from the post Baseline value (percentage of awake time spent "off"). Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Change From Baseline in Actual Hours of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline in awake time spent "On"(actual hours) is calculated as awake time spent "On" (hours) at the indicated visit minus awake time spent "On" (hours) at Baseline. Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

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

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline in awake time spent "On" without troublesome dyskinesias (actual hours) is calculated as [awake time spent "On" minus awake time spent "On" with troublesome dyskinesias] (hours) at visit minus [awake time spent "On" minus awake time spent "On" with troublesome dyskinesias] (hours) at Baseline. Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Number of Participants With an Improvement (Responder) in the Clinical Global Impression (CGI) Global Improvement Scale at Week 12

The CGI global improvement scale allows the investigator to rate the participant's total improvement since the beginning of treatment (Baseline). Scores on the scale range from 1 to 7 (1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse). Participants with a CGI global improvement score of <=2 (representing much improved or very much improved) were considered to be moderate improvement (responder). The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Number of Participants Remaining in the Study

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.

The Japanese 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. Number of participants achieving a 30% or greater and 20% or greater reduction from Baseline in UPDRS total part III score at Weeks 17, 21, 25, 37, 49 and 52,are presented using OC data. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The OC (observed Case) dataset was defined as the dataset consisting of observed data without any missing data imputation.

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

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline was calculated by subtracting the Baseline value (actual hours of awake time spent "off") from the week 17, 21, 25, 37, 49 and 52 value (proportion of awake time spent "off"). Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline.The analyses for long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data

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

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Percentage of awake time spent "off" is defined as sum of two days off time (hours) divided by sum of two days awake time (hours) and multiplied by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "off") from week 17, 21, 25, 37, 49 and 52 value (percentage of awake time spent "off"). Baseline is defined as the value at Week 13, If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline. The analyses for Long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data.

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

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline in awake time spent "On"(actual hours) is calculated as awake time spent "On" (hours) at the week 17, 21, 25, 37, 49 and 52 value minus awake time spent "On" (hours) at Baseline. Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline. The analyses for Long term phase was performed using the OC data. The OC (observed Case) dataset was defined as the dataset consisting of observed data without any missing data imputation.

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

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "on " periods and asleep in diary cards every day. Change from Baseline in awake time spent "On" without troublesome dyskinesias (actual hours) is calculated as [awake time spent "On" minus awake time spent "On" with troublesome dyskinesias] (hours) at visit minus [awake time spent "On" minus awake time spent "On" with troublesome dyskinesias] (hours) at Baseline. Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline. The analyses for Long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data

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

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "on " periods and asleep in diary cards every day. Percentage of awake time spent "on" is defined as sum of two days on time (hours) divided by sum of two days awake time (hours) and multiplified by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "on") from week 17, 21, 25, 37, 49 and 52 value (percentage of awake time spent "on"). Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing the first observed value post week 13 was used as a Baseline.The analyses for Long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data.

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

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Par. were asked to record the duration of their "on " periods and asleep in diary cards every day. Percentage of awake time spent "On" without troublesome dyskinesias is defined as sum of two days on time without troublesome dyskinesias ["On" time minus "On" time with troublesome dyskinesias] (hours) divided by sum of two days awake time (hours) and multiplified by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "On" without troublesome dyskinesias) from week 17, 21, 25, 37, 49 and 52 value (percentage of awake time spent "On" without troublesome dyskinesias). Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing the first observed value post week 13 was used as a Baseline.The analyses for Long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data.

Full Information

NCT ID

NCT01929317

First Posted

August 22, 2013

Last Updated

June 18, 2018

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01929317

Brief Title

A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.

Official Title

A Study ROP116991, Clinical Evaluation of 18 to 24mg/Day Ropinirole CR for Parkinson's Disease.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Terminated

Study Start Date

August 28, 2013 (Actual)

Primary Completion Date

September 16, 2014 (Actual)

Study Completion Date

June 9, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

Keywords

Ropinirole, Parkinson's disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

81 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ropinirole CR high-dose group

Arm Type

Experimental

Arm Description

Arm Title

Ropinirole CR maintenance group

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ropinirole CR 2mg tablet

Intervention Description

Ropinirole CR 2mg tablets will be supplied as white oval film-coated tablets.

Intervention Type

Drug

Intervention Name(s)

Ropinirole CR 8mg tablet

Intervention Description

Ropinirole CR 8mg tablets will be supplied as white oval film-coated tablets.

Intervention Type

Drug

Intervention Name(s)

Ropinirole CR matching Placebo tablet

Intervention Description

Ropinirole CR matching Placebo tablet tablets (containing no active ingredients) indistinguishable in appearance from Ropinirole CR 2 mg tablets.

Primary Outcome Measure Information:

Title

Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at Week 12 in the CR High-dose Group

Description

Time Frame

Baseline and Week 12

Secondary Outcome Measure Information:

Title

Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at the Indicated Visits

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

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

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

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

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

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

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

Description

The Japanese UPDRS assessed the status of PD participants objectively. Part 4 evaluated complications on 11 items, response for 4 items were scored numerically from 0-4 and response for other 7 items were Yes/No questions and responses are numerically scored as 0 for "No" and 1 for "Yes". The total score for the 11 items ranged from 0 to 23. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long-term Phase

Description

The Japanese UPDRS assessed the status of PD participants objectively. Part I evaluated mentation, behavior, and mood on 4 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 16. A higher score indicates more severe PD symptoms.Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data. Full Analysis Set 2 (FAS2) Population comprised of all participants in the FAS1 and shifted to Long-term Phase, excluding those participants who received no dose of study medication and participants without UPDRS part III total score data after supply of the investigational product.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

The Japanese UPDRS assesses the status of PD participants objectively. Part 2 evaluates activities of daily living on 13 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 52. A higher score indicates more severe PD symptoms.Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value at Week 13. If the value at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data."Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "On" state is defined as the state at which PD symptoms are well controlled by the drug. The score of UPDRS part 2 in off status is rated as '0' (Normal/None), if L-dopa adjunct participants do not have diurnal fluctuations.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

Mean Change From Baseline in UPDRS Part 3 Total Score at the Indicated Visits for Long Term Phase

Description

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49, 52

Title

Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long Term Phase

Description

The Japanese UPDRS assessed the status of PD participants objectively. Part 4 evaluated complications on 11 items, response for 4 items were scored numerically from 0-4 and response for other 7 items were Yes/No questions and responses are numerically scored as 0 for "No" and 1 for "Yes". The total score for the 11 items ranged from 0 to 23. A higher score indicates more severe PD symptoms.Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

Percent Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Long Term Phase

Description

The Japanese UPDRS assessed the status of PD participants objectively. Part I evaluated mentation, behavior, and mood on 4 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 16. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

The Japanese UPDRS assesses the status of PD participants objectively. Part 2 evaluates activities of daily living on 13 items, response for each item were scored numerically from 0-4. The total score for the 4 items ranged from 0 to 52. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value at Week 13. If the value at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data."Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "On" state is defined as the state at which PD symptoms are well controlled by the drug. The score of UPDRS part 2 in off status is rated as '0' (Normal/None), if L-dopa adjunct participants do not have diurnal fluctuations.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

Percent Change From Baseline in the Japanese UPDRS Part 3 Total Score at the Indicated Visits in the Long Term Phase

Description

The Japanese UPDRS assessed the status of PD participants objectively. Part 3 evaluated motor examination on 27 items, response for each items were scored numerically from 0-4. The total score for the 27 items ranged from 0 to 108. A higher score indicates more severe PD symptoms. Percent change from Baseline was calculated as Post baseline value minus Baseline value, divided by Baseline value and multiplied by 100. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The analyses performed using the OC data. In the OC data, no imputation was carried for any missing data.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

Percent Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Long-term Phase

Description

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

Change From Baseline in the Actual Hours of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Change From Baseline in the Percentage of Awake Time Spent "Off" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct

Description

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Percentage of awake time spent "off" is defined as sum of two days off time (hours) divided by sum of two days awake time (hours) and multiplied by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "off") from the post Baseline value (percentage of awake time spent "off"). Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Change From Baseline in Actual Hours of Awake Time Spent "On" at the Indicated Visits Only in Participants Who Received L-dopa Adjunct

Description

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

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

Description

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline in awake time spent "On" without troublesome dyskinesias (actual hours) is calculated as [awake time spent "On" minus awake time spent "On" with troublesome dyskinesias] (hours) at visit minus [awake time spent "On" minus awake time spent "On" with troublesome dyskinesias] (hours) at Baseline. Baseline is defined as the value at Week 0. The analyses for Dose Increase Effect Verification Phase was performed using the LOCF data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit.

Time Frame

Baseline, Weeks, 2, 4, 6, 8 and 12

Title

Number of Participants With an Improvement (Responder) in the Clinical Global Impression (CGI) Global Improvement Scale at Week 12

Description

Time Frame

Week 12

Title

Number of Participants Remaining in the Study

Time Frame

From the start of the study medication (Week 0) until Week 52

Title

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.

Description

The Japanese 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. Number of participants achieving a 30% or greater and 20% or greater reduction from Baseline in UPDRS total part III score at Weeks 17, 21, 25, 37, 49 and 52,are presented using OC data. Change from Baseline was calculated by subtracting the Baseline value from the post Baseline value. Baseline is defined as the value evaluated at Week 13. If the value evaluated at Week 13 was missing, then first observed value post Week 13 was used as Baseline. The OC (observed Case) dataset was defined as the dataset consisting of observed data without any missing data imputation.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49, 52

Title

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

Description

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline was calculated by subtracting the Baseline value (actual hours of awake time spent "off") from the week 17, 21, 25, 37, 49 and 52 value (proportion of awake time spent "off"). Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline.The analyses for long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Percentage of awake time spent "off" is defined as sum of two days off time (hours) divided by sum of two days awake time (hours) and multiplied by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "off") from week 17, 21, 25, 37, 49 and 52 value (percentage of awake time spent "off"). Baseline is defined as the value at Week 13, If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline. The analyses for Long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "off " periods and asleep in diary cards every day. Change from Baseline in awake time spent "On"(actual hours) is calculated as awake time spent "On" (hours) at the week 17, 21, 25, 37, 49 and 52 value minus awake time spent "On" (hours) at Baseline. Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing then first observed value post week 13 was used as a Baseline. The analyses for Long term phase was performed using the OC data. The OC (observed Case) dataset was defined as the dataset consisting of observed data without any missing data imputation.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Participants were asked to record the duration of their "on " periods and asleep in diary cards every day. Percentage of awake time spent "on" is defined as sum of two days on time (hours) divided by sum of two days awake time (hours) and multiplified by 100. Change from Baseline was calculated by subtracting the Baseline value (percentage of awake time spent "on") from week 17, 21, 25, 37, 49 and 52 value (percentage of awake time spent "on"). Baseline is defined as the value at Week 13. If the value evaluated at week 13 was missing the first observed value post week 13 was used as a Baseline.The analyses for Long term phase was performed using the OC data. In the OC data, no imputation was carried for any missing data.

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

Title

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

Description

Time Frame

Baseline (Week 13), Weeks 17, 21, 25, 37, 49 and 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 1) 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

466-8560

Country

Japan

Facility Name

GSK Investigational Site

City

Akita

ZIP/Postal Code

010-0874

Country

Japan

Facility Name

GSK Investigational Site

City

Aomori

ZIP/Postal Code

030-8553

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

070-8530

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

070-8644

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

672-8043

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

674-0081

Country

Japan

Facility Name

GSK Investigational Site

City

Iwate

ZIP/Postal Code

020-0878

Country

Japan

Facility Name

GSK Investigational Site

City

Iwate

ZIP/Postal Code

025-0075

Country

Japan

Facility Name

GSK Investigational Site

City

Kagawa

ZIP/Postal Code

760-0027

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

252-0392

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

600-8811

Country

Japan

Facility Name

GSK Investigational Site

City

Okayama

ZIP/Postal Code

703-8265

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

530-8480

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

578-8588

Country

Japan

Facility Name

GSK Investigational Site

City

Shizuoka

ZIP/Postal Code

416-0955

Country

Japan

Facility Name

GSK Investigational Site

City

Shizuoka

ZIP/Postal Code

433-8125

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Citations:

PubMed Identifier

28442303

Citation

Hattori N, Hasegawa K, Sato K, Mitsuyama E, Numachi Y. Clinical evaluation of ropinirole controlled-release formulation at 18-24 mg/day in Japanese patients with Parkinson's disease. Parkinsonism Relat Disord. 2017 Jul;40:33-39. doi: 10.1016/j.parkreldis.2017.04.005. Epub 2017 Apr 13.

Results Reference

derived

Links:

URL

https://www.clinicalstudydatarequest.com

Description

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Available IPD and Supporting Information:

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116991

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

116991

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.

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A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.

Parkinson Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial