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
Results First Received: September 1, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Parkinson Disease
Parkinson's Disease
Interventions: Drug: ropinirole PR/XR
Drug: ropinirole IR

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 157 participants who were enrolled in the Non-Inferiority Verification (NV) Phase entered into the Long-term Phase after completing the Prolonged Release/Extended Release (PR/XR) Switching Phase according to the study design. The remaining participants entered into the Down-titration Phase after completing the PR/XR Switching Phase.

Reporting Groups
  Description
Ropinirole PR-Ropinirole PR Participants received ropinirole prolonged release/extended release (PR/XR) tablets orally once daily. Participants firstly received matching PR/XR placebo tablets for 2 weeks and then received 2 milligram (mg) PR/XR tablets with a weekly dose increase to 4 mg at Week 4. Between Weeks 6 and 24, the dose was optionally increased at intervals of 2 weeks or longer up to 16 mg/day. In the PR/XR Switching Phase, administration of the PR/XR tablets was continued until Week 32 at the same dose level as that at the end of the Non-Inferiority Verification Phase. Participants who entered into the Long-term Phase continued to receive ropinirole PR/XR tablets until Week 54 at the same dose level as that at the end of the PR/XR Switching Phase. Participants who did not enter the Long-term Phase entered the Down-titration Phase after completion of the PR/XR Switching Phase.
Ropinirole IR-Ropinirole PR Participants received ropinirole immediate release (IR) tablets three times daily at the initial dose of 0.75 mg/day with a weekly dose increase to 3 mg/day at Week 4. Between Weeks 6 and 24, the dose was optionally increased at intervals of 2 weeks or longer up to 15 mg/day. Ropinirole IR tablets were administered until the night of the Week 24 visit and were replaced by ropinirole PR/XR tablets on the following morning, the morning of the first day of the PR/XR Switching Phase, at the same dose level. Participants who entered the Long-term Phase continued to receive ropinirole PR/XR until Week 54 at the same dose level as that at the end of the PR/XR Switching Phase. Participants who did not enter into the Long-term Phase entered the Down-titration Phase after completion of the PR/XR Switching Phase.

Participant Flow for 2 periods

Period 1:   NV and PR/XR Switching Phases
    Ropinirole PR-Ropinirole PR     Ropinirole IR-Ropinirole PR  
STARTED     156     146  
COMPLETED     124     117  
NOT COMPLETED     32     29  
Adverse Event                 22                 21  
Protocol Violation                 1                 1  
Physician Decision                 5                 2  
Withdrawal by Subject                 4                 5  

Period 2:   Long-term Phase
    Ropinirole PR-Ropinirole PR     Ropinirole IR-Ropinirole PR  
STARTED     73     84  
COMPLETED     68     79  
NOT COMPLETED     5     5  
Adverse Event                 3                 2  
Physician Decision                 1                 2  
Withdrawal by Subject                 1                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ropinirole PR-Ropinirole PR Participants received ropinirole prolonged release/extended release (PR/XR) tablets orally once daily. Participants firstly received matching PR/XR placebo tablets for 2 weeks and then received 2 milligram (mg) PR/XR tablets with a weekly dose increase to 4 mg at Week 4. Between Weeks 6 and 24, the dose was optionally increased at intervals of 2 weeks or longer up to 16 mg/day. In the PR/XR Switching Phase, administration of the PR/XR tablets was continued until Week 32 at the same dose level as that at the end of the Non-Inferiority Verification Phase. Participants who entered into the Long-term Phase continued to receive ropinirole PR/XR tablets until Week 54 at the same dose level as that at the end of the PR/XR Switching Phase. Participants who did not enter the Long-term Phase entered the Down-titration Phase after completion of the PR/XR Switching Phase.
Ropinirole IR-Ropinirole PR Participants received ropinirole immediate release (IR) tablets three times daily at the initial dose of 0.75 mg/day with a weekly dose increase to 3 mg/day at Week 4. Between Weeks 6 and 24, the dose was optionally increased at intervals of 2 weeks or longer up to 15 mg/day. Ropinirole IR tablets were administered until the night of the Week 24 visit and were replaced by ropinirole PR/XR tablets on the following morning, the morning of the first day of the PR/XR Switching Phase, at the same dose level. Participants who entered the Long-term Phase continued to receive ropinirole PR/XR until Week 54 at the same dose level as that at the end of the PR/XR Switching Phase. Participants who did not enter into the Long-term Phase entered the Down-titration Phase after completion of the PR/XR Switching Phase.
Total Total of all reporting groups

Baseline Measures
    Ropinirole PR-Ropinirole PR     Ropinirole IR-Ropinirole PR     Total  
Number of Participants  
[units: participants]
  156     146     302  
Age  
[units: Years]
Mean ± Standard Deviation
  69.3  ± 7.95     68.3  ± 8.22     68.8  ± 8.08  
Gender  
[units: Participants]
     
Female     93     81     174  
Male     63     65     128  
Race/Ethnicity, Customized  
[units: participants]
  156     146     302  



  Outcome Measures
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1.  Primary:   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) ]

2.  Secondary:   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) ]

3.  Secondary:   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) ]

4.  Secondary:   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) ]

5.  Secondary:   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) ]

6.  Secondary:   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) ]

7.  Secondary:   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) ]

8.  Secondary:   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) ]

9.  Secondary:   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) ]

10.  Secondary:   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) ]

11.  Secondary:   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) ]

12.  Secondary:   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) ]

13.  Secondary:   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) ]

14.  Secondary:   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) ]

15.  Secondary:   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) ]

16.  Secondary:   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) ]

17.  Secondary:   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) ]

18.  Secondary:   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) ]

19.  Secondary:   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) ]

20.  Secondary:   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) ]

21.  Secondary:   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) ]

22.  Secondary:   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) ]

23.  Secondary:   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) ]

24.  Secondary:   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) ]

25.  Secondary:   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) ]

26.  Secondary:   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) ]

27.  Secondary:   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) ]

28.  Secondary:   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) ]

29.  Secondary:   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) ]

30.  Secondary:   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) ]

31.  Secondary:   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) ]

32.  Secondary:   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) ]

33.  Secondary:   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) ]

34.  Secondary:   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) ]

35.  Secondary:   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) ]

36.  Secondary:   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) ]

37.  Secondary:   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) ]

38.  Secondary:   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) ]

39.  Secondary:   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) ]

40.  Secondary:   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) ]

41.  Secondary:   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) ]

42.  Secondary:   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) ]

43.  Secondary:   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 ]

44.  Secondary:   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 ]

45.  Secondary:   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 ]

46.  Secondary:   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 ]

47.  Secondary:   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 ]

48.  Secondary:   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 ]

49.  Secondary:   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 ]

50.  Secondary:   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 ]

51.  Secondary:   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 ]

52.  Secondary:   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 ]

53.  Secondary:   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 ]

54.  Secondary:   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 ]

55.  Secondary:   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 ]

56.  Secondary:   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 ]

57.  Secondary:   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 ]

58.  Secondary:   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 ]

59.  Secondary:   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 ]

60.  Secondary:   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 ]

61.  Secondary:   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 ]

62.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


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