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Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

Primary Purpose

Parkinson Disease

Status

Completed

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

ropinirole PR/XR

ropinirole IR

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Ropinirole, advanced Parkinson's disease, L-dopa adjunctive therapy

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 with advanced Parkinson's disease (PD) with severity of the modified Hoehn & Yahr criteria Stages II-IV.
Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening phase and demonstrating lack of control with L-dopa therapy in the following circumstances. Wearing-off phenomena. On-off fluctuations. Delayed-on/No on phenomena. Not adequately controlled on L-dopa
QTc<450 millisecond (msec) or <480msec for patients with Bundle Branch Block - values based on either single ECG values or triplicate electrocardiogram (ECG) averaged QTc values obtained over a brief recording period.
Age:20 years 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 one's own)
Sex: either sex. Female 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, agree to further pregnancy testing at the time points determined in study assessments and procedures and practice one of the following methods of contraception from the screening visit until the end of the follow-up examination. Abstinence. Injectable progestogen. Implants of levonorgestrel. Estrogenic vaginal ring. Percutaneous contraceptive patches. Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (foam /gel / film / cream / suppository)
Both inpatient and outpatient status.

Inclusion Criteria at the start of the non-inferiority verification phase

-Patients whose Unified Parkinson's Disease Rating Scale (UPDRS) PartIII total (on) scores is 10 points or more at week 0.

Exclusion Criteria:

Late stage advanced subjects demonstrating incapacitating peak dose or biphasic dyskinesia on their stable dose of L-dopa.
Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder). The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences (Pharmaceutical affairs bureau/Safety division (PAB/SD) Notification No. 80, dated 29 June 1992).
Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).
Patients with a current or history of drug abuse or alcoholism.
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.
Patients with chronic hepatitis typeB and/or type C which is positive of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody.
Patients with a history of drug allergy to ropinirole hydrochloride (HCl).
Patients with a current or history of cancer or malignant tumor.
Others whom the investigator (subinvestigator) considers ineligible for the study.

Exclusion criteria at the start of the non-inferiority verification phase

Patients with severe dementia (e.g. score 3 or 4 of the UPDRS item 1 (Intellectual Impairment))
Patients with current or history of major psychosis (e.g. schizophrenia or psychotic depression) core 3 or 4 of the UPDRS item 2 (thought disorder) or item 3(depression).
Patients who have used any dopamine agonist within 4 weeks prior to the non-inferiority verification phase
Patients who have been treated with the following drugs at 4 weeks or earlier before the start of the non-inferiority verification phase, and whose treatment regimen of the drug has been changed. Anticholinergic agents: trihexyphenidyl hydrochloride (e.g. Artane®), piroheptine hydrochloride (Trimol®), mazaticol hydrochloride (Pentona®), metixene hydrochloride (Cholinfall®), biperiden hydrochloride (Akineton®), profenamine (Parkin®), amantadine hydrochloride (e.g. Symmetrel®),droxidopa (Dops®), citicoline (e.g. Nicholin®), selegiline hydrochloride (FP®), entacapone, (comutan®) zonisamide, Estrogens: e.g. estriol (e.g. Estriel®), CYP1A2 inhibitors: Ciprofloxacin HCl (e.g. Ciproxan®, enoxacin and fluvoxamine).
Patients who have been treated with any other investigational drug within 12 weeks prior to the treatment phase.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ropinirolePR-PR group

ropiniroleIR-PR group

Arm Description

Outcomes

Primary Outcome Measures

Mean Change From Week 0 (Baseline) in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score at the Final Assessment Point (FAP) (up to Week 24) in the Non-Inferiority Verification Phase

The Japanese UPDRS assesses the status of Parkinson's Disease (PD) patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0. Participants who withdrew before Week 2 and who had only one observation for the part III total score were not included in the analysis.

Secondary Outcome Measures

Percentage of Responders on the Japanese UPDRS Part III Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Thirty percent responders were defined as participants with a 30 percent or greater reduction from Week 0 in the Japanese UPDRS Part III total score. Twenty percent responders were defined as participants with a 20 percent or greater reduction from Week 0 in the Japanese UPDRS Part III total score. On-treatment last observations within the phase were carried forward as FAP values of the phase. FAP values do not include values of Weeks 0, 1, and 2; participants who withdrew before Week 2 and who had only one measurement for the part III total score were not included in the analysis.

Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0.

Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is defined as the state at which PD symptoms are well controlled by the drug. Mean change from Week 0 was calculated as the total score at FAP minus the score at Week 0.

Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 24 in the Non-Inferiority Verification Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0. Particpants with only one observation for the part II (at "Off") total score were not included in the analysis.

Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0.

Japanese UPDRS Part I Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Japanese UPDRS Part II (at "On") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Japanese UPDRS Part II (at "Off") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Japanese UPDRS Part III Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Japanese UPDRS Part IV Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Percentage of Responders on the Clinical Global Impression-Improvement (CGI-I) at FAP (up to Week 24) in the Non-Inferiority Verification Phase

The CGI-I assesses the participant's improvement or worsening of PD from Baseline with the following eight grades: 0 = Not Assessed, 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse. Responders are defined as those participants with scores of very much improved or much improved.

Percentage of Responders in Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Responders were defined as participants with a 20 percent or greater reduction on change from Week 0 in Off time (percentage).

Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Responders were defined as participants with a 20 percent or greater reduction in percent change from Week 0 in Off time (percentage).

Mean Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Mean change from Week 0 in Off time (actual hours) was calculated as Off time (hours) at FAP minus Off time (hours) at Week 0.

Mean Change From Week 0 in Percentage of Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "Off" time is measured as a proportion using the following formula: (Sum of two days off time [hours]/Sum of two days awake time [hours]) x 100. Change from Week 0 in Off time is measured using the following formula: Off time (proportion) at FAP minus Off time (proportion) at Week 0.

Mean Percent Change From Week 0 in Percentage of Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "Off" time is measured as a proportion using the following formula: (Sum of two days off time [hours]/Sum of two days awake time [hours]) x 100. Percent change from Week 0 in Off time (proportion) is measured using the following formula: (Change from Week 0 in Off time [proportion]/Off time [proportion] at Week 0) x 100.

Mean Change From Week 0 in Awake Time Spent "On" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Mean Change from Week 0 in On time (actual hours) was calculated as On time (hours) at FAP minus On time (hours) at Week 0. Participants who had only one observation for On time were not included in the analysis.

Mean Change From Week 0 in Percentage of Awake Time Spent "On" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"On" state is defined as the state at which PD symptoms are well controlled by the drug. "On" time is measured as a proportion using the following formula: (Sum of two days On time [hours]/Sum of two days awake time [hours]) x 100. Change from Week 0 in On time is measured using the following formula: On time (proportion) at FAP minus On time (proportion) at Week 0. Participants who had only one observation for On time were not included in the analysis.

Mean Change From Week 0 in Awake Time Spent "On" With Troublesome Dyskinesias at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Troublesome dyskinesia is defined as dyskinesia that interferes with the participant's daily activity. Mean change from Week 0 in On time with troublesome dyskinesias (actual hours) was calculated as On time with troublesome dyskinesias (hours) at FAP minus On time with troublesome dyskinesias (hours) at Week 0. Participants who had only one observation for On time with troublesome dyskinesias were not included in the analysis.

Mean Change From Week 0 in Percentage of Awake Time Spent "On" With Troublesome Dyskinesias at FAP (up to Week 24) in the Non-Inferiority Verification Phase

"On" time with troublesome dyskinesias is measured as a proportion using the following formula: (Sum of two days On time with troublesome dyskinesias [hours]/Sum of two days awake time [hours]) x 100. Change from Week 0 in On time with troublesome dyskinesias is measured using the following formula: On time with troublesome dyskinesias (proportion) at FAP minus On time with troublesome dyskinesias (proportion) at Week 0. Participants who had only one observation for On time with troublesome dyskinesias were not included in the analysis.

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Week 0 and FAP (up to Week 24) in the Non-Inferiority Verification Phase

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "On" state is defined as the state at which PD symptoms are well controlled by the drug.

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Week 0 and FAP (up to Week 24) in the Non-Inferiority Verification Phase

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug.

Percentage of Participants Remaining in the Study on the Indicated Days During the Non-Inferiority Verification Phase in the Ropinirole PR-Ropinirole PR Group

The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 24) was the event, and participants who had completed the phase were censored.

Percentage of Participants Remaining in the Study on the Indicated Days During the Non-Inferiority Verification Phase in the Ropinirole IR-Ropinirole PR Group

Mean Change From Week 24 (Period Baseline) in the Japanese UPDRS Part I Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included.

Mean Change From Week 24 in the Japanese UPDRS Part II (at "On") Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is defined as the state at which PD symptoms are well controlled by the drug. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24.

Mean Change From Week 24 in the Japanese UPDRS Part II (at "Off") Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is where PD symptoms are not adequately controlled by the drug. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included in the analysis.

Mean Change From Week 24 in the Japanese UPDRS Part III Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24.

Mean Change From Week 24 in the Japanese UPDRS Part IV Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24.

Japanese UPDRS Part I Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Japanese UPDRS Part II (at "On") Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Japanese UPDRS Part II (at "Off") Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Only participants who had "off" state were included in the analysis.

Japanese UPDRS Part III Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. One participant whose observation could not be obtained at Week 24 was not included in the analysis for Week 24.

Japanese UPDRS Part IV Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. One participant whose observation could not be obtained at Week 24 was not included in the analysis for Week 24.

Mean Change From Week 24 in Awake Time Spent "Off" at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Mean change from Week 24 in Off time (actual hours) was calculated as Off time (hours) at FAP minus Off time (hours) at Week 24. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included in the analysis.

Mean Change From Week 24 in Percentage of Awake Time Spent "Off" at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "Off" time is measured as a proportion using the following formula: (Sum of two days off time [hours]/Sum of two days awake time [hours]) x 100. Change from Week 24 in Off time is measured using the following formula: Off time (proportion) at FAP minus Off time (proportion) at Week 24. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included in the analysis.

Mean Change From Week 24 in Awake Time Spent "On" With Troublesome Dyskinesias at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Troublesome dyskinesia is defined as dyskinesia that interferes with the participant's daily activity. Mean change from Week 24 on On time with troublesome dyskinesias (actual hours) was calculated as On time with troublesome dyskinesias (hours) at FAP minus On time with troublesome dyskinesias (hours) at Week 24. Participants who had 0 hour as On time with troublesome dyskinesias at Week 24 were excluded from the analysis.

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Only participants who had "off" state were included in the analysis.

Percentage of Participants Remaining in the Study on the Indicated Days During the PR/XR Switching Phase in the Ropinirole PR-Ropinirole PR Group

The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 32) was the event, and participants who had completed the phase were censored.

Percentage of Participants Remaining in the Study on the Indicated Days During the PR/XR Switching Phase in the Ropinirole IR-Ropinirole PR Group

Percentage of Responders on the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Thirty percent responders were defined as participants with a 30 percent or greater reduction from Week 0 (Baseline) in the Japanese UPDRS Part III total score. Twenty percent responders were defined as participants with a 20 percent or greater reduction from Week 0 in the Japanese UPDRS Part III total score.

Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Mean change from Week 0 was calculated as the total score at Week 54 minus the total score at Week 0.

Mean Change From Week 0 in the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Mean change from Week 0 was calculated as the total score at Week 54 minus the total score at Week 0.

Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Japanese UPDRS Part I Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Japanese UPDRS Part II (at "On") Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Japanese UPDRS Part II (at "Off") Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Japanese UPDRS Part III Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Japanese UPDRS Part IV Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Percentage of Responders on the CGI-I at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

The CGI-I assesses the participant's improvement or worsening of PD from baseline with the following eight grades: 0 = Not Assessed, 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse. Responders are defined as those participants with scores of very much improved or much improved.

Percentage of Responders in Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase

Mean Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Mean Change From Week 0 in Percentage of Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Mean Change From Week 0 in Awake Time Spent "On" With Troublesome Dyskinesias at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Troublesome dyskinesia is defined as dyskinesia that interferes with the participant's daily activity. Mean change from Week 0 in On time with troublesome dyskinesias (actual hours) was calculated as On time with troublesome dyskinesias (hours) at Week 54 minus On time with troublesome dyskinesias (hours) at Week 0.

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug.

Percentage of Participants Remaining in the Study on the Indicated Days During the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 54) was the event, and participants who had completed the study were censored.

Full Information

NCT ID

NCT00823836

First Posted

January 15, 2009

Last Updated

November 30, 2016

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT00823836

Brief Title

Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

Official Title

Clinical Evaluation of Ropinirole PR/XR Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

March 2009 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

December 2010 (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

To investigate the efficacy and the safety of ropinirole PR/XR tablets to ropinirole immediate release (IR) tablets with advanced Parkinson's disease in conjunction with L-dopa in a double-blind, parallel group comparison study.

6. Conditions and Keywords

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

Parkinson Disease

Keywords

Ropinirole, advanced Parkinson's disease, L-dopa adjunctive therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

302 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ropinirolePR-PR group

Arm Type

Experimental

Arm Title

ropiniroleIR-PR group

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

ropinirole PR/XR

Other Intervention Name(s)

ropinirole IR-PR group

Intervention Description

Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group. The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day). Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage. Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind. Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.

Intervention Type

Drug

Intervention Name(s)

ropinirole IR

Intervention Description

Primary Outcome Measure Information:

Title

Description

Time Frame

Week 0 and FAP (up to Week 24)

Secondary Outcome Measure Information:

Title

Percentage of Responders on the Japanese UPDRS Part III Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

FAP (up to Week 24)

Title

Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 24 in the Non-Inferiority Verification Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0. Particpants with only one observation for the part II (at "Off") total score were not included in the analysis.

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Japanese UPDRS Part I Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Japanese UPDRS Part II (at "On") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Japanese UPDRS Part II (at "Off") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Japanese UPDRS Part III Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Japanese UPDRS Part IV Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Percentage of Responders on the Clinical Global Impression-Improvement (CGI-I) at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

FAP (up to Week 24)

Title

Percentage of Responders in Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

FAP (up to Week 24)

Title

Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

FAP (up to Week 24)

Title

Mean Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in Percentage of Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Percent Change From Week 0 in Percentage of Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "Off" time is measured as a proportion using the following formula: (Sum of two days off time [hours]/Sum of two days awake time [hours]) x 100. Percent change from Week 0 in Off time (proportion) is measured using the following formula: (Change from Week 0 in Off time [proportion]/Off time [proportion] at Week 0) x 100.

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in Awake Time Spent "On" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in Percentage of Awake Time Spent "On" at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in Awake Time Spent "On" With Troublesome Dyskinesias at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Mean Change From Week 0 in Percentage of Awake Time Spent "On" With Troublesome Dyskinesias at FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Week 0 and FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

Time Frame

Week 0 and FAP (up to Week 24)

Title

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Week 0 and FAP (up to Week 24) in the Non-Inferiority Verification Phase

Description

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug.

Time Frame

Week 0 and FAP (up to Week 24)

Title

Percentage of Participants Remaining in the Study on the Indicated Days During the Non-Inferiority Verification Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

0-175 days (up to Week 24)

Title

Percentage of Participants Remaining in the Study on the Indicated Days During the Non-Inferiority Verification Phase in the Ropinirole IR-Ropinirole PR Group

Description

Time Frame

0-175 days (up to Week 24)

Title

Mean Change From Week 24 (Period Baseline) in the Japanese UPDRS Part I Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in the Japanese UPDRS Part II (at "On") Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is defined as the state at which PD symptoms are well controlled by the drug. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in the Japanese UPDRS Part II (at "Off") Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is where PD symptoms are not adequately controlled by the drug. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included in the analysis.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in the Japanese UPDRS Part III Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in the Japanese UPDRS Part IV Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. Mean change from Week 24 was calculated as the total score at FAP minus the total score at Week 24.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Japanese UPDRS Part I Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Japanese UPDRS Part II (at "On") Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Japanese UPDRS Part II (at "Off") Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Only participants who had "off" state were included in the analysis.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Japanese UPDRS Part III Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. One participant whose observation could not be obtained at Week 24 was not included in the analysis for Week 24.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Japanese UPDRS Part IV Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. One participant whose observation could not be obtained at Week 24 was not included in the analysis for Week 24.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in Awake Time Spent "Off" at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in Percentage of Awake Time Spent "Off" at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

"Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. "Off" time is measured as a proportion using the following formula: (Sum of two days off time [hours]/Sum of two days awake time [hours]) x 100. Change from Week 24 in Off time is measured using the following formula: Off time (proportion) at FAP minus Off time (proportion) at Week 24. Participants whose observation could not be obtained after Week 24 because of their premature withdrawal or other reasons were not included in the analysis.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Mean Change From Week 24 in Awake Time Spent "On" With Troublesome Dyskinesias at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Troublesome dyskinesia is defined as dyskinesia that interferes with the participant's daily activity. Mean change from Week 24 on On time with troublesome dyskinesias (actual hours) was calculated as On time with troublesome dyskinesias (hours) at FAP minus On time with troublesome dyskinesias (hours) at Week 24. Participants who had 0 hour as On time with troublesome dyskinesias at Week 24 were excluded from the analysis.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase

Description

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Only participants who had "off" state were included in the analysis.

Time Frame

Week 24 and FAP (from Week 26 up to Week 32)

Title

Percentage of Participants Remaining in the Study on the Indicated Days During the PR/XR Switching Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

0-89 days within the PR/XR Switching Phase (between Weeks 24 and 32)

Title

Percentage of Participants Remaining in the Study on the Indicated Days During the PR/XR Switching Phase in the Ropinirole IR-Ropinirole PR Group

Description

Time Frame

0-89 days within the PR/XR Switching Phase (between Weeks 24 and 32)

Title

Percentage of Responders on the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Week 54

Title

Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug. Mean change from Week 0 was calculated as the total score at Week 54 minus the total score at Week 0.

Time Frame

Weeks 0 and 54

Title

Mean Change From Week 0 in the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Mean change from Week 0 was calculated as the total score at Week 54 minus the total score at Week 0.

Time Frame

Weeks 0 and 54

Title

Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Japanese UPDRS Part I Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Japanese UPDRS Part II (at "On") Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Japanese UPDRS Part II (at "Off") Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Japanese UPDRS Part III Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Japanese UPDRS Part IV Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Percentage of Responders on the CGI-I at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Week 54

Title

Percentage of Responders in Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Week 54

Title

Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase

Description

Time Frame

Week 54

Title

Mean Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Mean Change From Week 0 in Percentage of Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Mean Change From Week 0 in Awake Time Spent "On" With Troublesome Dyskinesias at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

"On" state is defined as the state at which PD symptoms are well controlled by the drug. Troublesome dyskinesia is defined as dyskinesia that interferes with the participant's daily activity. Mean change from Week 0 in On time with troublesome dyskinesias (actual hours) was calculated as On time with troublesome dyskinesias (hours) at Week 54 minus On time with troublesome dyskinesias (hours) at Week 0.

Time Frame

Weeks 0 and 54

Title

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

Weeks 0 and 54

Title

Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for disease severity: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. "Off" state is defined as the state at which PD symptoms are not adequately controlled by the drug.

Time Frame

Weeks 0 and 54

Title

Percentage of Participants Remaining in the Study on the Indicated Days During the Long-term Phase in the Ropinirole PR-Ropinirole PR Group

Description

Time Frame

0-385 days (up to Week 54)

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 with advanced Parkinson's disease (PD) with severity of the modified Hoehn & Yahr criteria Stages II-IV. Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening phase and demonstrating lack of control with L-dopa therapy in the following circumstances. Wearing-off phenomena. On-off fluctuations. Delayed-on/No on phenomena. Not adequately controlled on L-dopa QTc<450 millisecond (msec) or <480msec for patients with Bundle Branch Block - values based on either single ECG values or triplicate electrocardiogram (ECG) averaged QTc values obtained over a brief recording period. Age:20 years 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 one's own) Sex: either sex. Female 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, agree to further pregnancy testing at the time points determined in study assessments and procedures and practice one of the following methods of contraception from the screening visit until the end of the follow-up examination. Abstinence. Injectable progestogen. Implants of levonorgestrel. Estrogenic vaginal ring. Percutaneous contraceptive patches. Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (foam /gel / film / cream / suppository) Both inpatient and outpatient status. Inclusion Criteria at the start of the non-inferiority verification phase -Patients whose Unified Parkinson's Disease Rating Scale (UPDRS) PartIII total (on) scores is 10 points or more at week 0. Exclusion Criteria: Late stage advanced subjects demonstrating incapacitating peak dose or biphasic dyskinesia on their stable dose of L-dopa. Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder). The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences (Pharmaceutical affairs bureau/Safety division (PAB/SD) Notification No. 80, dated 29 June 1992). Patients with symptomatic postural hypotension. (e.g. dizziness and syncope). Patients with a current or history of drug abuse or alcoholism. 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. Patients with chronic hepatitis typeB and/or type C which is positive of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody. Patients with a history of drug allergy to ropinirole hydrochloride (HCl). Patients with a current or history of cancer or malignant tumor. Others whom the investigator (subinvestigator) considers ineligible for the study. Exclusion criteria at the start of the non-inferiority verification phase Patients with severe dementia (e.g. score 3 or 4 of the UPDRS item 1 (Intellectual Impairment)) Patients with current or history of major psychosis (e.g. schizophrenia or psychotic depression) core 3 or 4 of the UPDRS item 2 (thought disorder) or item 3(depression). Patients who have used any dopamine agonist within 4 weeks prior to the non-inferiority verification phase Patients who have been treated with the following drugs at 4 weeks or earlier before the start of the non-inferiority verification phase, and whose treatment regimen of the drug has been changed. Anticholinergic agents: trihexyphenidyl hydrochloride (e.g. Artane®), piroheptine hydrochloride (Trimol®), mazaticol hydrochloride (Pentona®), metixene hydrochloride (Cholinfall®), biperiden hydrochloride (Akineton®), profenamine (Parkin®), amantadine hydrochloride (e.g. Symmetrel®),droxidopa (Dops®), citicoline (e.g. Nicholin®), selegiline hydrochloride (FP®), entacapone, (comutan®) zonisamide, Estrogens: e.g. estriol (e.g. Estriel®), CYP1A2 inhibitors: Ciprofloxacin HCl (e.g. Ciproxan®, enoxacin and fluvoxamine). Patients who have been treated with any other investigational drug within 12 weeks prior to the treatment phase.

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

454-0933

Country

Japan

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

460-0008

Country

Japan

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

465-8620

Country

Japan

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

489-8642

Country

Japan

Facility Name

GSK Investigational Site

City

Akita

ZIP/Postal Code

010-0874

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

260-8712

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

270-1337

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

270-2251

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

279-0021

Country

Japan

Facility Name

GSK Investigational Site

City

Chiba

ZIP/Postal Code

290-0003

Country

Japan

Facility Name

GSK Investigational Site

City

Ehime

ZIP/Postal Code

791-0295

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

800-0296

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

814-0180

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

816-0864

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

819-8585

Country

Japan

Facility Name

GSK Investigational Site

City

Fukushima

ZIP/Postal Code

963-8052

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

068-0027

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

651-2273

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

670-0981

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

674-0081

Country

Japan

Facility Name

GSK Investigational Site

City

Ibaraki

ZIP/Postal Code

310-0011

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

232-0066

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

247-8533

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

251-0038

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

252-0392

Country

Japan

Facility Name

GSK Investigational Site

City

Kanagawa

ZIP/Postal Code

253-8558

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

600-8811

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

601-1495

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

610-0113

Country

Japan

Facility Name

GSK Investigational Site

City

Kyoto

ZIP/Postal Code

616-8255

Country

Japan

Facility Name

GSK Investigational Site

City

Miyagi

ZIP/Postal Code

983-8520

Country

Japan

Facility Name

GSK Investigational Site

City

Nagano

ZIP/Postal Code

399-0157

Country

Japan

Facility Name

GSK Investigational Site

City

Nagano

ZIP/Postal Code

399-8695

Country

Japan

Facility Name

GSK Investigational Site

City

Nagasaki

ZIP/Postal Code

859-3615

Country

Japan

Facility Name

GSK Investigational Site

City

Nara

ZIP/Postal Code

632-8552

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

543-8555

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

560-8552

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

570-8507

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

578-8588

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

590-0132

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

596-8522

Country

Japan

Facility Name

GSK Investigational Site

City

Osaka

ZIP/Postal Code

598-0048

Country

Japan

Facility Name

GSK Investigational Site

City

Saitama

ZIP/Postal Code

343-0032

Country

Japan

Facility Name

GSK Investigational Site

City

Saitama

ZIP/Postal Code

359-1141

Country

Japan

Facility Name

GSK Investigational Site

City

Shiga

ZIP/Postal Code

524-0022

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

420-8688

Country

Japan

Facility Name

GSK Investigational Site

City

Tochigi

ZIP/Postal Code

329-0498

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

113-8431

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

136-0075

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

183-8524

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

202-0004

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.

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

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

106066

Available IPD/Information Comments

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

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

106066

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

106066

Available IPD/Information Comments

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

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

106066

Available IPD/Information Comments

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

Available IPD/Information Type

Annotated Case Report Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

106066

Available IPD/Information Comments

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

Learn more about this trial

Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

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Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

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