Long-term Study Of Ropinirole In Restless Legs Syndrome | NCT00329602

Label	Type	Description	Intervention Names
Double-blind for 12 to 26 Weeks	Placebo Comparator	Double-blind (Ropinirole:Placebo) for 12 to 26 weeks	Drug: Placebo Drug: Ropinirole
Open-label ropinirole for 40-Weeks	Other	Open label ropinirole for 40 weeks	Drug: Ropinirole

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Matching Placebo	Double-blind for 12 to 26 Weeks
Ropinirole

Measure	Description	Time Frame
Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26	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.	Baseline and Weeks 12 and 26
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases	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.	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

Measure	Description	Time Frame
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female subjects, between the ages of 18 and 79, inclusive

A female is eligible to enter and participate in the study if she is of:

Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
Childbearing potential, has a negative result on all required pregnancy tests prior to randomisation, and agrees to an acceptable contraceptive method.
- Subjects with a diagnosis of idiopathic RLS using the RLS Diagnostic Clinical Interview and the International RLS Study Group (IRLSSG) Diagnostic Criteria during the Screening Visit.
- Subjects have had RLS symptoms with a history of a minimum of 15 RLS episodes during the previous month. If this is not possible due to the subject being on previous medication to treat RLS the investigator should ensure that the subject should have experienced 4-5 episodes of RLS symptoms during the last 7 days of the wash-out phase (see below). The subject must discontinue and wash-out any previous medication for the treatment of RLS or sleep prior to the Baseline Visit (Day 0). The minimum discontinuation period for wash-out is generally 5 half-lives of the medication or 7 consecutive evenings/nights medication-free prior to baseline, whichever is the longer period.
- During the Wash-out and Screening Phase, RLS symptoms must be present for at least 4 of the last 7 nights immediately prior to the Baseline Visit (e.g., any combination of evenings and /or nights for = 4 days).
- Subjects with a total score = 24 on the IRLS Rating Scale at baseline (Day 0).
- Subjects with RLS symptoms that cause significant sleep impairment based on clinical judgment and guided by subject response to Question 4 of the IRLS Rating Scale (e.g., ordinarily this will include a response of (3) severe or (4) very severe sleep disturbance) at the Baseline Visit OR RLS symptoms that cause severe/very severe discomfort in the limbs based on clinical judgment and guided by subject response to Question 1 of the IRLS Rating Scale (e.g., this will include a response of (3) severe or (4) very severe discomfort in limbs) at the Baseline Visit (Day 0).
- Subjects must be experiencing RLS symptoms requiring treatment at night-time.
- Subjects must have given written informed consent prior to any specific study procedures.

Exclusion criteria:

Subjects suffering from augmentation and/ or 'end of treatment' rebound RLS symptoms at baseline (Day 0). Augmentation is defined as RLS symptoms that occurred while on treatment and occur earlier in the afternoon/evening than they did before, symptoms which are more severe than when not treated, symptoms which start after less time at rest than they did before treatment, or symptoms which involve other parts of the body, such as the arms or trunk. 'End of treatment' rebound describes worsening of symptoms from baseline that occur after pharmacological treatment is stopped.
Subjects with a previous history of augmentation.
Subjects who have exhibited intolerance to ropinirole or any other dopamine agonist.
Subjects requiring treatment of daytime RLS symptoms (daytime defined as 10:00 hours until 17:00 hours).
Signs of secondary RLS (e.g., end stage renal disease, iron deficient anaemia or pregnancy at Baseline Visit).
Subjects with a serum ferritin level of < 10 mcg/L (ng/mL) at Screening Visit.
Subjects who suffer from a primary sleep disorder other than RLS that may significantly affect the symptoms of RLS (e.g. narcolepsy, sleep terror disorder, sleepwalking disorder, breathing related sleep disorder).
Subjects diagnosed with movement disorders (e.g., Parkinson's Disease, dyskinesias, and dystonias).
Subjects who have medical conditions which could affect efficacy assessments or clinically significant or unstable medical conditions that present a safety concern. These may include, but are not limited to, the following disorders: diabetes, peripheral neuropathy, rheumatoid arthritis, fibromyalgia syndrome, symptomatic orthostatic hypotension, severe cardiovascular disease, hepatic or renal failure, pleuro-pulmonary fibrosis, major psychotic illness.
Subjects having a clinically significant abnormal laboratory value, ECG, or physical examination findings not resolved by the time of the baseline examinations (Day 0). Abnormal 12-lead ECG findings include, but are not limited to, the following: myocardial ischemia, clinically significant conduction abnormalities, or clinically significant arrhythmias.
Subjects with a diastolic blood pressure = 110mmHg or = 50mmHg or systolic blood pressure = 180mmHg or = 90mmHg at the Screening or Baseline Visit.
Subjects with a history of alcohol or substance abuse within the past year.
Subjects taking any medication known to induce drowsiness, affect RLS or sleep and which have not been discontinued prior to the Baseline Visit. These medications include the following:

Atypical and typical antipsychotics, anticonvulsants, opioids (including propoxyphene and oxycodone), anxiolytics, all sedatives/hypnotics (including benzodiazepines), lithium, oral neuroleptics, stimulants (including methylphenidate), dopamine agonists (including ropinirole), dopamine antagonists (e.g., typical neuroleptics, metoclopramide), levodopa/carbidopa, clonidine, and sedating antihistamines (e.g., chlorpheniramine, diphenhydramine, hydroxyzine) or any preparations containing these antihistamines.

The minimum discontinuation period is generally 5 half lives or 7 consecutive evenings/nights medication free, prior to baseline, whichever is the longer period. Exceptions to this general rule are: fluoxetine, monoamine oxidase inhibitors: 4 weeks.

For subjects entering the 40-week, open-label treatment phase, the GSK Medical Monitor can be contacted to discuss individual cases where adherence to the above may not have occurred.

Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT) and/or any drug known to substantially inhibit CYP1A2 (e.g., ciprofloxacin, cimetidine, fluvoxamine, HRT) or induce CYP1A2 (e.g., tobacco, omeprazole) within 7 days prior to enrolment. Subjects already on these agents may be enrolled, but must remain on stable doses of the agents from 7 days prior to enrolment through to the follow-up visit at the end of the study.
Night workers or any others whose sleeping habits are incompatible with the study design, or who would be required to make significant changes to their bedtime during the course of the study.
Participation in any clinical drug or device trial in the one month prior to the Baseline Visit.
Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedules or other study procedures.
Women who have a positive pregnancy test or who are lactating.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Camperdown	New South Wales	2050	Australia
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
22328464	Background	Garcia-Borreguero D, Hogl B, Ferini-Strambi L, Winkelman J, Hill-Zabala C, Asgharian A, Allen R. Systematic evaluation of augmentation during treatment with ropinirole in restless legs syndrome (Willis-Ekbom disease): results from a prospective, multicenter study over 66 weeks. Mov Disord. 2012 Feb;27(2):277-83. doi: 10.1002/mds.24889. Epub 2012 Jan 4.
23938061

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
ROR104836	Informed Consent Form	View IPD

ID	Title	Description
FG000	Double-blind Placebo	Matching placebo tablets
FG001	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

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26

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.

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.

Posted

Least Squares Mean

Standard Error

points on a scale

Baseline and Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Units	Counts
Participants	OG000205 OG001196

Title

Denominators

Categories

Week 12, n=165, 164

Title	Measurements
	OG000-12.1± 0.70 OG001-14.2± 0.71

Week 26, n=119, 123

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Repeated Measures Mixed Model	Adjusted for baseline IRLS Rating Scale total score, treatment group, visit, visit by treatment group interaction, and center group.	0.039	P-value is for Week 12.						95							Superiority or Other
OG000 OG001

Secondary

Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at 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.

Posted

Least Squares Mean

Standard Error

points on a scale

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

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Secondary

Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at 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.

Posted

Least Squares Mean

Standard Error

points on a scale

Baseline and Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Secondary

Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at 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.

Posted

Least Squares Mean

Standard Error

hours

Baseline and Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Units	Counts

Secondary

Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at 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.

Posted

Least Squares Mean

Standard Error

points on a scale

Baseline and Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Secondary

Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at 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.

Posted

Least Squares Mean

Standard Error

points on a scale

Baseline and Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Units	Counts

Secondary

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

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.

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

Posted

Number

percentage of participants

Weeks 1, 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Units	Counts
Participants

Secondary

Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study

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.

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

Posted

Number

participants

Baseline to Week 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Units	Counts
Participants	OG000

Secondary

Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26

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).

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.

Posted

Number

participants

Week 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Secondary

Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase

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.

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

Posted

Median

95% Confidence Interval

days

Baseline to Week 26

ID	Title	Description
OG000	Double-blind Placebo	Matching placebo tablets
OG001	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

Units	Counts

Secondary

Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67

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.

Posted

Number

participants

Week 67

ID	Title	Description
OG000	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

Units	Counts
Participants	OG000

Primary

Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases

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.

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

Posted

Number

participants

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

ID	Title	Description
OG000	Overall Study
OG001	Double-blind Placebo	Matching placebo tablets
OG002	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
OG003	Open-label Ropinirole IR

Secondary

Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67

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.

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.

Posted

Mean

Standard Deviation

points on a scale

Baseline and Week 67

ID	Title	Description
OG000	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

Units	Counts
Participants	OG000

Post-Hoc

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

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.

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

Posted

Least Squares Mean

Standard Error

Points on a scale

Baseline and Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Double-Blind Placebo participants (receiving matching placebo tablets) who were not in the center groups with the highest or lowest treatment effects
OG001	Double-blind Ropinirole IR	Double-Blind Ropinirole participants (receiving 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) who were not in the center groups with the highest or lowest treatment effects

Post-Hoc

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

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.

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.

Posted

Number

Number of responders

Weeks 12 and 26

ID	Title	Description
OG000	Double-blind Placebo	Double-Blind Placebo participants (receiving matching placebo tablets) who were not excluded from the IRLS post-hoc analysis
OG001	Double-blind Ropinirole IR	Double-Blind Ropinirole participants (receiving 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) who were not excluded from the IRLS post-hoc analysis

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Peptic ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Appendicitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Post procedural infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Fallopian tube cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Ovarian cyst torsion	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Gallbladder disorder	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0011 affected197 at risk EG0020 affected269 at risk
Cerebral infarction	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected207 at risk EG0010 affected197 at risk EG0020 affected269 at risk
Bursa calcification	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Brain stem ischaemia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Vertigo	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Chest pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG0010 affected197 at risk EG0021 affected269 at risk

ID	Term
D009422	Nervous System Diseases
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D020447	Parasomnias
D001523	Mental Disorders
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Title	Description
BG000	Double-Blind Placebo	Matching placebo tablets
BG001	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
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-blind Placebo	Matching placebo tablets	6	207	71	207
EG001	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	6	197	123	197
EG002	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	11	269	122	269

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00016 affected207 at risk EG00183 affected197 at risk EG00267 affected269 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG00023 affected207 at risk EG00129 affected197 at risk EG00220 affected269 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00014 affected207 at risk EG00128 affected197 at risk EG00229 affected269 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00014 affected207 at risk EG00121 affected197 at risk EG00233 affected269 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0006 affected207 at risk EG00120 affected197 at risk EG00216 affected269 at risk
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected207 at risk EG00122 affected197 at risk EG00213 affected269 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG00011 affected207 at risk EG0017 affected197 at risk EG0029 affected269 at risk
Insomnia	Psychiatric disorders	MedDRA	Systematic Assessment	EG0005 affected207 at risk EG00112 affected197 at risk EG0021 affected269 at risk
Diarrhea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected207 at risk EG00110 affected197 at risk EG0023 affected269 at risk
Somnolence	Nervous system disorders	MedDRA	Systematic Assessment	EG0004 affected207 at risk EG0019 affected197 at risk EG00214 affected269 at risk