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

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

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

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) ]