Trial Outcomes & Findings for Long-term Study Of Ropinirole In Restless Legs Syndrome (NCT NCT00329602)

Last Updated: 2017-03-23

Results Overview

A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. A negative change from baseline indicates improvement, and a negative treatment difference indicates a benefit of Ropinirole IR over placebo. The primary assessment was made by calculating the difference in the average score obtained at Baseline with scores at Week 12 and then Week 26.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

404 participants

Primary outcome timeframe

Baseline and Weeks 12 and 26

Results posted on

2017-03-23

Participant Flow

Participants (par.) could enter the Open-Label (OL) phase at the end of the Double-Blind (DB) phase. If a par. did not complete the DB phase due to lack of efficacy, he/she could also be considered for entry into the OL phase if the investigator considered it appropriate and the par. met the protocol-defined criteria in describing lack of efficacy.

Participant milestones

Participant milestones
Measure	Double-blind Placebo Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
26-Week Double-Blind Treatment Phase STARTED	207	197	0
26-Week Double-Blind Treatment Phase COMPLETED	88	98	0
26-Week Double-Blind Treatment Phase NOT COMPLETED	119	99	0
40-Week Open-Label Treatment Phase STARTED	0	0	269
40-Week Open-Label Treatment Phase COMPLETED	0	0	233
40-Week Open-Label Treatment Phase NOT COMPLETED	0	0	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind Placebo Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
26-Week Double-Blind Treatment Phase Did not complete phase; reason unknown	119	99	0
40-Week Open-Label Treatment Phase Adverse Event	0	0	20
40-Week Open-Label Treatment Phase Lost to Follow-up	0	0	1
40-Week Open-Label Treatment Phase Protocol Violation	0	0	2
40-Week Open-Label Treatment Phase Lack of Efficacy	0	0	9
40-Week Open-Label Treatment Phase Captured as Other	0	0	4

Baseline Characteristics

Long-term Study Of Ropinirole In Restless Legs Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-Blind Placebo n=207 Participants Matching placebo tablets	Double-Blind Ropinirole IR n=197 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Total n=404 Participants Total of all reporting groups
Age, Continuous	55.9 years STANDARD_DEVIATION 11.53 • n=5 Participants	56.5 years STANDARD_DEVIATION 11.97 • n=7 Participants	56.2 years STANDARD_DEVIATION 11.73 • n=5 Participants
Sex: Female, Male Female	132 Participants n=5 Participants	124 Participants n=7 Participants	256 Participants n=5 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	73 Participants n=7 Participants	148 Participants n=5 Participants
Race/Ethnicity, Customized White	204 participants n=5 Participants	197 participants n=7 Participants	401 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Hawaiian or other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 Week 12, n=165, 164	-14.2 points on a scale Standard Error 0.71	-12.1 points on a scale Standard Error 0.70	—	—
Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 Week 26, n=119, 123	-15.9 points on a scale Standard Error 0.76	-13.4 points on a scale Standard Error 0.77	—	—

PRIMARY outcome

Timeframe: During 15-month study duration at scheduled (Weeks 16, 20, 26, or early withdrawal for DB phase; Weeks 39, 47, 55, 63, 67, or early withdrawal for the OL phase) and unscheduled (26-week DB phase and 40-week OL phase) visits

Population: Safety Population: all participants who received at least one dose of study medication

Clinically meaningful augmentation and early morning rebound (EMR) were assessed and confirmed by an independent Adjudication Board. EMR describes the development of RLS symptoms during the early morning, following therapeutic intervention. EMR is differentiated from augmentation, in which the earlier onset of symptoms occurs in the evening.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=207 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=404 Participants Matching placebo tablets	Double-blind Ropinirole IR n=197 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR n=269 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases Confirmed augmentation	1 participants	15 participants	7 participants	8 participants
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases Clinically meaningful augmentation	1 participants	11 participants	5 participants	5 participants
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases Confirmed EMR	1 participants	7 participants	4 participants	2 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 4, 8, 16, and 20

A 10-item, participant-reported scale covering different RLS symptoms. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. The primary assessment from this study was made by calculating the difference in the average score obtained at Baseline with scores at Weeks 1, 4, 8, 16, and 20. Scores were adjusted for baseline IRLS total score, treatment group, visit, visit by treatment group interaction, and center group.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 Week 1, n=198, 194	-7.8 points on a scale Standard Error 0.52	-5.5 points on a scale Standard Error 0.52	—	—
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 Week 4, n=183, 180	-13.6 points on a scale Standard Error 0.60	-10.5 points on a scale Standard Error 0.60	—	—
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 Week 8, n=168, 170	-15.3 points on a scale Standard Error 0.66	-13.0 points on a scale Standard Error 0.66	—	—
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 Week 16, n=137, 144	-15.0 points on a scale Standard Error 0.74	-12.6 points on a scale Standard Error 0.75	—	—
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 Week 20, n=125, 132	-15.7 points on a scale Standard Error 0.77	-12.3 points on a scale Standard Error 0.78	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population. Domain values are presented on a 0-100 scale, where a higher score means a greater degree of the attribute implied by the scale name. Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 Sleep disturbance, Week 12, n=153, 143	-24.0 points on a scale Standard Error 1.67	-15.0 points on a scale Standard Error 1.62	—	—
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 Sleep disturbance, Week 26, n=105, 97	-24.6 points on a scale Standard Error 1.87	-16.4 points on a scale Standard Error 1.80	—	—
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 Sleep adequacy, Week 12, n=153, 143	22.8 points on a scale Standard Error 1.98	15.0 points on a scale Standard Error 1.91	—	—
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 Sleep adequacy, Week 26, n=105, 97	26.0 points on a scale Standard Error 2.25	14.9 points on a scale Standard Error 2.16	—	—
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 Daytime somnolence, Week 12, n=153, 143	-11.4 points on a scale Standard Error 1.33	-7.5 points on a scale Standard Error 1.28	—	—
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 Daytime somnolence, Week 26, n=105, 97	-11.4 points on a scale Standard Error 1.65	-9.1 points on a scale Standard Error 1.59	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population.Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 Week 12, n=153, 143	0.7 hours Standard Error 0.11	0.5 hours Standard Error 0.10	—	—
Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 Week 26, n=105, 97	0.7 hours Standard Error 0.11	0.5 hours Standard Error 0.11	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

The Johns Hopkins RLS QoL Questionnaire is a disease-specific instrument that assesses the impact of RLS on the daily life, emotional well-being, social life, and work life of participants. The overall life impact score for the John Hopkins RLS QoL scale ranges from a lowest possible score of 0 to a highest possible score of 100. Higher scores represent better quality of life. Scores were adjusted for baseline RLS Quality of Life score, treatment group, visit, visit by treatment interaction, and center group.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 Week 12, n=149, 141	18.0 points on a scale Standard Error 1.33	14.0 points on a scale Standard Error 1.29	—	—
Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 Week 26, n=103, 94	18.5 points on a scale Standard Error 1.41	16.5 points on a scale Standard Error 1.35	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

The MOS SF-36 is a generic QoL instrument measuring functional status and well-being. Positive change from baseline for all domains indicates improvement. For all MOS SF-36 domains, the minimum and maximum scores are 0 and 100, respectively, for the transformed scale. Scores were adjusted for baseline domain score, treatment group, visit, visit by treatment interaction, and center group.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Bodily pain, Week 12, n=149, 142	14.4 points on a scale Standard Error 1.76	12.3 points on a scale Standard Error 1.72	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Bodily pain, Week 26, n=104, 94	14.0 points on a scale Standard Error 2.11	13.3 points on a scale Standard Error 2.01	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 General health, Week 12, n=149, 142	4.5 points on a scale Standard Error 1.11	3.0 points on a scale Standard Error 1.08	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 General health, Week 26, n=104, 94	4.1 points on a scale Standard Error 1.37	2.6 points on a scale Standard Error 1.31	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Mental health, Week 12, n=149, 142	7.6 points on a scale Standard Error 1.26	5.0 points on a scale Standard Error 1.22	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Mental health, Week 26, n=104, 94	6.2 points on a scale Standard Error 1.31	4.6 points on a scale Standard Error 1.25	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Physical functioning, Week 12, n=149, 142	5.5 points on a scale Standard Error 1.25	2.4 points on a scale Standard Error 1.22	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Physical functioning, Week 26, n=104, 94	2.6 points on a scale Standard Error 1.54	3.5 points on a scale Standard Error 1.48	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Role emotional, Week 12, n=149, 142	7.0 points on a scale Standard Error 1.67	5.1 points on a scale Standard Error 1.62	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Role emotional, Week 26, n=104, 94	6.6 points on a scale Standard Error 1.74	5.9 points on a scale Standard Error 1.66	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Role physical, Week 12, n=149, 142	7.7 points on a scale Standard Error 1.71	5.2 points on a scale Standard Error 1.66	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Role physical, Week 26, n=104, 94	6.7 points on a scale Standard Error 1.94	7.5 points on a scale Standard Error 1.85	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Social functioning, Week 12, n=149, 142	9.8 points on a scale Standard Error 1.62	6.3 points on a scale Standard Error 1.58	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Social functioning, Week 26, n=104, 94	8.8 points on a scale Standard Error 1.63	7.1 points on a scale Standard Error 1.56	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Vitality, Week 12, n=149, 142	9.3 points on a scale Standard Error 1.41	8.0 points on a scale Standard Error 1.37	—	—
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 Vitality, Week 26, n=104, 94	9.2 points on a scale Standard Error 1.61	6.0 points on a scale Standard Error 1.54	—	—

SECONDARY outcome

Timeframe: Weeks 1, 12 and 26

Population: Intention-to-Treat (ITT) Population. Analysis is based on the observed cases for each visit.

The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=192 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=192 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 Week 1, n=192, 192	50 percentage of participants	39 percentage of participants	—	—
Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 Week 12, n=165, 160	109 percentage of participants	86 percentage of participants	—	—
Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 Week 26, n=112, 108	91 percentage of participants	72 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline to Week 26

Lack of efficacy is defined as up to a 10% improvement in the IRLS Rating Scale total score from the participant's Baseline value and at least 12 weeks of treatment during the double-blind phase.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study	3 participants	2 participants	—	—

SECONDARY outcome

Timeframe: Week 26

Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Data are presented for the participants still in the study and assessed at Week 26, which is less than those randomised at baseline.

The CGI-S scale is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-S allows the investigator to rate the severity of the participant's illness considering their total clinical experience with the subject population being studied and on all information available at the time of rating. The scale is rated from 1-7 (1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severly ill; 7 = among the most extremely ill participants).

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=108 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=112 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26	50 participants	50 participants	—	—

SECONDARY outcome

Timeframe: Baseline to Week 26

The median time to first CGI-I response of much/very much improved was calculated. The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=196 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=205 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase	21 days Interval 14.0 to 21.0	28 days Interval 22.0 to 33.0	—	—

SECONDARY outcome

Timeframe: Week 67

Population: Open-Label (OL) ITT Population: all participants who were enrolled into the OL Phase of the study, received at least one dose of OL study medication, and had a baseline IRLS total score and on-treatment IRLS assessment. Data are presented for participants still in the study and assessed at Week 26, which is less than those randomized at baseline.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=200 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67	—	184 participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 67

Population: Open-Label ITT Population: all participants who were enrolled into the Open-Label Phase of the study, received at least one dose of Open-Label study medication, and had a baseline IRLS total score and on-treatment IRLS assessment. Analysis is based on the observed cases for each visit.

A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4, with 0 representing the absence of a problem and 4 reflecting a very severe problem. The best and worst possible scores are 0 and 40, respectively. The primary assessment was made by calculating the difference in the average score obtained at Baseline with score at Week 67.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=268 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67	—	-20.4 points on a scale Standard Deviation 8.36	—	—

POST_HOC outcome

Timeframe: Baseline and Weeks 12 and 26

Population: ITT Population excluding the two center groups with the most extreme treatment effects. Analysis is based on the observed cases for each visit.

A post-hoc analysis of the primary outcome measure, exploring the variation in treatment effects across center groups by excluding those with the most extreme treatment effects, was conducted. Centers were grouped into five center groups.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=134 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=136 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect Week 12, n=136, 134	-13.8 Points on a scale Standard Error 0.79	-12.2 Points on a scale Standard Error 0.78	—	—
Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect Week 26, n=103, 105	-15.7 Points on a scale Standard Error 0.83	-14.0 Points on a scale Standard Error 0.84	—	—

POST_HOC outcome

Timeframe: Weeks 12 and 26

Population: ITT Population excluding the same two center groups as in the IRLS post-hoc analysis. Analysis is based on the observed cases for each visit.

A post-hoc analysis of CGI-I, exploring the variation in treatment effects across center groups by excluding the same two center groups as in the IRLS post-hoc analysis, was conducted. Centers were grouped into five center groups.

Outcome measures

Outcome measures
Measure	Double-blind Ropinirole IR n=134 Participants Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Double-blind Placebo n=136 Participants Matching placebo tablets	Double-blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-label Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect Week 12, n=136, 134	93 Number of responders	75 Number of responders	—	—
Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect Week 26, n=99, 96	82 Number of responders	63 Number of responders	—	—

Adverse Events

Double-blind Placebo

Serious events: 6 serious events

Other events: 71 other events

Deaths: 0 deaths

Double-blind Ropinirole IR

Serious events: 6 serious events

Other events: 123 other events

Deaths: 0 deaths

Open-Label Ropinirole IR

Serious events: 11 serious events

Other events: 122 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind Placebo n=207 participants at risk Matching placebo tablets	Double-blind Ropinirole IR n=197 participants at risk Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-Label Ropinirole IR n=269 participants at risk Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Gastrointestinal disorders Abdominal pain	0.48% 1/207	0.00% 0/197	0.00% 0/269
Gastrointestinal disorders Abdominal pain upper	0.00% 0/207	0.51% 1/197	0.00% 0/269
Gastrointestinal disorders Peptic ulcer	0.00% 0/207	0.51% 1/197	0.00% 0/269
Infections and infestations Appendicitis	0.48% 1/207	0.00% 0/197	0.00% 0/269
Infections and infestations Post procedural infection	0.00% 0/207	0.51% 1/197	0.00% 0/269
Infections and infestations Pyelonephritis	0.48% 1/207	0.00% 0/197	0.00% 0/269
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/207	0.51% 1/197	0.00% 0/269
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/207	0.51% 1/197	0.00% 0/269
Reproductive system and breast disorders Fallopian tube cyst	0.00% 0/207	0.51% 1/197	0.00% 0/269
Reproductive system and breast disorders Ovarian cyst	0.00% 0/207	0.51% 1/197	0.00% 0/269
Reproductive system and breast disorders Ovarian cyst torsion	0.48% 1/207	0.00% 0/197	0.00% 0/269
Hepatobiliary disorders Gallbladder disorder	0.48% 1/207	0.00% 0/197	0.00% 0/269
Injury, poisoning and procedural complications Joint dislocation	0.48% 1/207	0.00% 0/197	0.00% 0/269
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/207	0.51% 1/197	0.00% 0/269
Nervous system disorders Cerebral infarction	0.48% 1/207	0.00% 0/197	0.00% 0/269
Vascular disorders Hypertension	0.48% 1/207	0.00% 0/197	0.00% 0/269
Musculoskeletal and connective tissue disorders Bursa calcification	0.00% 0/207	0.00% 0/197	0.37% 1/269
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/207	0.00% 0/197	0.37% 1/269
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/207	0.00% 0/197	0.37% 1/269
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/207	0.00% 0/197	0.37% 1/269
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/207	0.00% 0/197	0.37% 1/269
Injury, poisoning and procedural complications Head injury	0.00% 0/207	0.00% 0/197	0.37% 1/269
Nervous system disorders Brain stem ischaemia	0.00% 0/207	0.00% 0/197	0.37% 1/269
Nervous system disorders Syncope	0.00% 0/207	0.00% 0/197	0.37% 1/269
Ear and labyrinth disorders Vertigo	0.00% 0/207	0.00% 0/197	0.37% 1/269
General disorders Chest pain	0.00% 0/207	0.00% 0/197	0.37% 1/269
Hepatobiliary disorders Cholelithiasis	0.00% 0/207	0.00% 0/197	0.37% 1/269
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/207	0.00% 0/197	0.37% 1/269

Other adverse events

Other adverse events
Measure	Double-blind Placebo n=207 participants at risk Matching placebo tablets	Double-blind Ropinirole IR n=197 participants at risk Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day	Open-Label Ropinirole IR n=269 participants at risk Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day
Gastrointestinal disorders Nausea	7.7% 16/207	42.1% 83/197	24.9% 67/269
Nervous system disorders Headache	11.1% 23/207	14.7% 29/197	7.4% 20/269
General disorders Fatigue	6.8% 14/207	14.2% 28/197	10.8% 29/269
Infections and infestations Nasopharyngitis	6.8% 14/207	10.7% 21/197	12.3% 33/269
Nervous system disorders Dizziness	2.9% 6/207	10.2% 20/197	5.9% 16/269
Gastrointestinal disorders Vomiting	0.00% 0/207	11.2% 22/197	4.8% 13/269
Musculoskeletal and connective tissue disorders Back pain	5.3% 11/207	3.6% 7/197	3.3% 9/269
Psychiatric disorders Insomnia	2.4% 5/207	6.1% 12/197	0.37% 1/269
Gastrointestinal disorders Diarrhea	2.4% 5/207	5.1% 10/197	1.1% 3/269
Nervous system disorders Somnolence	1.9% 4/207	4.6% 9/197	5.2% 14/269

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER