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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00823836
First received: January 15, 2009
Last updated: October 13, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Parkinson Disease
Parkinson's Disease
Drug: ropinirole PR/XR
Drug: ropinirole IR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Clinical Evaluation of Ropinirole PR/XR Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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.

  • Japanese UPDRS Part II (at "On") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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.

  • Japanese UPDRS Part II (at "Off") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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.

  • Japanese UPDRS Part III Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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.

  • Japanese UPDRS Part IV Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Responders on the Clinical Global Impression-Improvement (CGI-I) at FAP (up to Week 24) in the Non-Inferiority Verification Phase [ Time Frame: FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 0 and FAP (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0-175 days (up to Week 24) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0-175 days (up to Week 24) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase [ Time Frame: Week 24 and FAP (from Week 26 up to Week 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0-89 days within the PR/XR Switching Phase (between Weeks 24 and 32) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0-89 days within the PR/XR Switching Phase (between Weeks 24 and 32) ] [ Designated as safety issue: No ]
    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 Responders on the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group [ Time Frame: Week 54 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 Week 54 minus the total score at Week 0.

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 Week 54 minus the total score at Week 0.

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 Week 54 minus the total score at Week 0.

  • Japanese UPDRS Part I Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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.

  • Japanese UPDRS Part III Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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.

  • Japanese UPDRS Part IV Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Responders on the CGI-I at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group [ Time Frame: Week 54 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 54 ] [ Designated as safety issue: No ]
    "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 change from Week 0 in Off time (percentage).

  • Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase [ Time Frame: Week 54 ] [ Designated as safety issue: No ]
    "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 percent change from Week 0 in Off time (percentage).

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    "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 Week 54 minus Off time (hours) at Week 0.

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    "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 Week 54 minus Off time (proportion) at Week 0.

  • 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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    "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 [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group [ Time Frame: Weeks 0 and 54 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0-385 days (up to Week 54) ] [ Designated as safety issue: No ]
    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.


Enrollment: 302
Study Start Date: March 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ropinirolePR-PR group Drug: ropinirole PR/XR

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.

Other Name: ropinirole IR-PR group
Active Comparator: ropiniroleIR-PR group Drug: ropinirole PR/XR

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.

Other Name: ropinirole IR-PR group
Drug: ropinirole IR

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.


  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823836

  Show 54 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00823836     History of Changes
Other Study ID Numbers: 106066
Study First Received: January 15, 2009
Results First Received: September 1, 2011
Last Updated: October 13, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
Ropinirole, advanced Parkinson's disease, L-dopa adjunctive therapy

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Ropinirole
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014