Clinical Evaluation of Ropinirole IR (Immediate Release)... | NCT00996944

Label	Type	Description	Intervention Names
Ropinirole IR	Experimental		Drug: Ropinirole immediate release (IR)
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Ropinirole immediate release (IR)	Drug	Subjects completing the screening period will be randomized (1:1) to receive the IR or placebo for 12 weeks. The treatment will be started at the initial dose of 0.25 mg/day within 1 to 3 hours before bedtime. The maximum available dose is 3 mg/day. For all subjects completing short-term period and entering the long-term treatment period, the open-label treatment will be started from IR 0.25 mg/ day regardless of dose levels during short-term period. The dose will be upward titrated from 0.25 mg/day to 0.5 mg/day and after that in increments of 0.5 mg/day until sufficient efficacy is obtained (targeting "much improved" or "very much improved" in the CGI-I) without safety/tolerability problem.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 0 and Week 12	The IRLS rating scale is an investigator-rated scale consisting of 10 questions with a choice of 5 responses each. These responses are numerically scored from 0 (the least severe response) to 4 (the most severe response). The IRLS rating scale total score is calculated by summing the individual response scores. The highest possible score is 40, which represents the most severe RLS; the lowest possible score is 0, which represents an absence of RLS. A total of 17 participants were prematurely withdrawn from the study before Week 12.	Week 0 and Week 12
IRLS Rating Scale Total Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)	The IRLS rating scale is an investigator-rated scale consisting of 10 questions with a choice of 5 responses each. These responses are numerically scored from 0 (the least severe response) to 4 (the most severe response). The IRLS rating scale total score is calculated by summing the individual response scores. The highest possible score is 40, which represents the most severe RLS; the lowest possible score is 0, which represents an absence of RLS. A total of 17 participants were prematurely withdrawn from the study before Week 12, and 2 participants had missing DBT WD data.	DBT WD (up to Week 12)

Secondary Outcomes

Measure	Description	Time Frame
IRLS Rating Scale Total Score for Participants Who Withdrew in the Long-term Treatment Period (LONG WD)	The IRLS rating scale is an investigator-rated scale consisting of 10 questions with a choice of 5 responses each. These responses are numerically scored from 0 (the least severe response) to 4 (the most severe response). The IRLS rating scale total score is calculated by summing the individual response scores. The highest possible score is 40, which represents the most severe RLS; the lowest possible score is 0, which represents an absence of RLS.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

at Week -1 (at the screening visit)

Patients who are diagnosed with symptomatic restless legs syndrome associated with Chronic kidney disease (CKD) managed with haemodialysis (including haemofiltration and haemodiafiltration). RLS are diagnosed based on the International RLS Study Group's (IRLSSG) Diagnostic Criteria.
Patients with chronic kidney disease (CKD) on haemodialysis (including haemofiltration and haemodiafiltration) for at least 3 months prior to the screening period with and receiving an adequate haemodialysis prescription (i.e. single-pool Kt/V >1.0. Shinzato calculating formula [Shinzato, 1994] using in Japanese Society for Dialysis Therapy will be used.)
Patients aged ≥18 years and <80 years.
Patients who have had RLS symptoms for 20 days or more on or after 28 days before the start of the screening period. However, patients who have been receiving drug therapy for RLS before the start of the screening period do not apply to this criterion when meeting the conditions below: The patient's drug therapy (excluding Anxiolytics and Hypnotics and sedatives medication) for RLS can be discontinued at the time of starting the screening period. For RLS symptoms in the subject was considered to have continued for 20 days or more on or after 28 days before the start of the drug treatment for RLS.
QTc criteria (QTc [b or f], mechanical or manual reread, male or female): Patients with QTc <450 msec or <480 msec for patients with bundle branch block (BBB) -values based on either single electrocardiogram (ECG) values or triplicate ECG averaged QTc values obtained over a brief recording period.
Male or female patients. A female subject is eligible to enter and participate in the study if she:

Is of non-childbearing potential or Is of child-bearing potential, is not lactating and agrees to use one of GlaxoSmithKline (GSK)-specified highly effective methods for avoiding pregnancy: abstinence, oral contraceptives, either combined or progestogen alone (see "Permitted medications"), injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring (see "Permitted medications"), percutaneous contraceptive patches (see "Permitted medications"), intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label, male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject, double barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] plus spermicidal agent [foam/gel/film/cream/suppository]).

Outpatients
Patients who are able to give informed written consent in person. Legal representative also should give informed written consent, if patients are under twenty years old.

at Week 0 (at the start of the treatment period)

Patients who experience RLS symptoms for at least 4 days within 7 days before the start of the treatment period.
Patients who have sleep disturbance associated with RLS. Patients who answered as 3 (severe) or 4 (very severe) to Question 4 (Sleep disturbance) in the IRLS Rating Scale.
Patients whose IRLS Rating Scale total scores are 15 points or more.
Liver function tests: Patients with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 * ULN (upper limit of normal); and bilirubin ≤ 1.5 * ULN (isolated bilirubin > 1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) at week -1(at the screening visit). ULN of ALT(GTP) and AST(GOT) is 20 IU/L [Kurokawa, 2002].
A female subject has a negative pregnancy test at week -1(at the screening visit).

Exclusion Criteria:

at Week -1 (at the screening visit)

Patients with signs of primary RLS (Patients who have developed RLS symptoms since kidney function was normal)
Patients with following sleep disorder not associated with RLS e.g. narcolepsy, sleep terror disorder, sleepwalking disorder, breathing related sleep disorder
Patients with complication of movement disorder (e.g. Parkinson's disease, dyskinesia, dystonia, etc)
Patients with severe hepatic/cardiac/pulmonary disorder or haematopoietic disorder other than those on haemodialysis (including haemofiltration and haemodiafiltration). The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences" (Pharmaceutical affairs bureau/Safety division(PAB/SD) Notification No. 80, dated 29 June 1992).
Patients with a history of malignancies within the past 5 years, with the exception of basal cell carcinoma of the skin or carcinoma in situ of cervix.
Patients with a medical history or complication of substance abuse (e.g. alcohol or drug) or dependency of substance for the last one year.
Patients with supine systolic blood pressure (SBP) of <100 mmHg or >190 mmHg or supine diastolic blood pressure (DBP) of ≥120 mmHg before the dialysis which will be conducted after the longest interval,at the screening visit.
Patients intolerant to ropinirole hydrochloride (HCl) or other dopamine agonists.
Patients for whom ropinirole HCl or other dopamine agonists are considered to be of safety concern by the investigator/subinvestigator
Patients with a history of augmentation or End-of-dose-rebound in the early morning after medications of dopamine agonists (including ropinirole HCl) and/or L-Dopa. Augmentation is defined as follows: RLS symptoms that occurred while on treatment and occur ≧ 2 hours earlier 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. Symptoms which involve other parts of the body, such as the arms or trunk.
Patients without night time sleeping habit (e.g. night-shift worker, etc) and those who must drastically change the habitual bedtime during the study duration.
Patients who have participated in another clinical study of an investigational product or medical device within the last 12 weeks prior to the start of the screening period.
Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study. (Instructions should be given to women of childbearing potential to practice adequate contraception even if they have no plan for pregnancy).
Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
Presence of hepatitis B surface antigen (HBsAg), positive Hepatitis C test result within 3 months of screening.
Patients who have medical conditions which, in the opinion of investigator/subinvestigator could affect efficacy and safety assessment. This may include the following disorders: fibromyalgia syndrome, rheumatoid arthritis, symptomatic orthostatic hypotension, hepatic failure, pulmonary fibrosis.
Subject is unable to discontinue prohibited medications during the Screening period.
Subjects who know they will imminently receive a transplant
Patients who have changed the dose or administration method of Anxiolytics or Hypnotics and sedatives within the last 4 weeks prior to the start of the screening period and or Patients who used more than two drugs.
Others whom the investigator/subinvestigator considers ineligible for the study.

at Week 0 (start of the treatment period)

Patients with supine SBP of <100 mmHg or >190 mmHg or supine DBP of ≥120 mmHg before the dialysis which will be conducted after the longest interval, at Week 0 (start of the treatment period).
Patients who have started treatment with medications including an estrogen drug product, a drug that is known to substantially induce or inhibit CYP1A2, an antihistamine (for ocular instillation or dermal application, or a preparation containing fexofenadine HCl or loratadine), Anxiolytics, Hypnotics and sedatives or who have changed the dose or administration method of such medications between Week -1 (start of the screening period) and Week 0 (start of the treatment period).
Patients whose serum ferritin level is <10 μg/L (ng/mL) at the screening visit.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Aichi		440-0035	Japan
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
	Background	This study has not been published in the scientific literature.

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
113079	Individual Participant Data Set	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ropinirole IR-Ropinirole IR	Participants received immediate-release (IR) tablets of ropinirole once daily for 12 weeks in the double-blind treatment period. The dose of investigational product (IP) was upward titrated from 0.25 milligrams (mg)/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed Clinical Global Impression-Improvement [CGI-I]) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 0 and Week 12

The IRLS rating scale is an investigator-rated scale consisting of 10 questions with a choice of 5 responses each. These responses are numerically scored from 0 (the least severe response) to 4 (the most severe response). The IRLS rating scale total score is calculated by summing the individual response scores. The highest possible score is 40, which represents the most severe RLS; the lowest possible score is 0, which represents an absence of RLS. A total of 17 participants were prematurely withdrawn from the study before Week 12.

Full Analysis Set (FAS): participants who were progressed to the treatment phase, but excluding those who did not have the target indication, those who had not received at least one dose of the investigational product, and those who did not have any measured efficacy data after initiation of the study treatment.

Posted

Mean

Standard Deviation

units on a scale

Week 0 and Week 12

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received immediate-release (IR) tablets of ropinirole once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 milligram (mg)/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed Clinical Global Impression - Improvement [CGI-I]) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR	Participants received matching placebo to ropinirole IR in the double-blind treatment period. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants received ropinirole IR tablets in the same way as in the ropinirole IR-ropinirole IR group.

Units	Counts
Participants	OG00022 OG00112

Title

Denominators

Categories

Week 0, n=22, 12

Title	Measurements
	OG00026.0± 5.51 OG00124.0± 3.64

Week 12, n=12, 5

Title	Measurements
	OG000

Secondary

IRLS Rating Scale Total Score for Participants Who Withdrew in the Long-term Treatment Period (LONG WD)

FAS. One participant in each group had no measurement data and thus was not included in the analysis. These two participants were withdrawn from the study without receiving the IP in the long-term treatment period.

Posted

Mean

Standard Deviation

units on a scale

LONG WD (up to Week 64)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

Number of Participants With the Indicated Clinical Global Impression-Improvement (CGI-I) Scores at Week 12

The CGI-I assesses the participant's improvement or worsening of RLS from baseline with the following eight grades: 0 = Not Assessed, 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse.

FAS. Participants withdrawn from the study before Week 12 were not included in the analysis.

Posted

Number

participants

Week 12

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR	Participants received matching placebo to ropinirole IR in the double-blind treatment period. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants received ropinirole IR tablets in the same way as in the ropinirole IR-ropinirole IR group.

Secondary

Number of Participants With the Indicated CGI-I Scores for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)

FAS. Participants with missing DBT WD data were not included in the analysis.

Posted

Number

participants

DBT WD (up to Week 12)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR

Secondary

Number of Participants With the Indicated CGI-I Scores for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)

FAS. Participants with no measurement data in the long-term treatment period because of their premature withdrawal without receiving the IP in that period were not included in the analysis.

Posted

Number

participants

LONG WD (up to Week 64)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR

Secondary

Johns Hopkins Restless Legs Syndrome Quality of Life (RLSQOL) Questionnaire Overall Life Impact Score at Week 0 and Week 12

The RLSQOL questionnaire is a participant-rated questionnaire designed to assess the impact of RLS on the lives of participants. It consists of 18 items, 10 of which contribute to a single summary score (overall life impact). The response for each item is coded from 1 to 5, with 1 representing the best quality of life and 5 representing the worst quality of life. The lowest possible overall life impact score is 0, and the highest possible overall life impact score is 100. The score of 100 represents the best possible quality of life.

FAS. Participants withdrawn from the study before Week 12 were not included in the analysis.

Posted

Mean

Standard Deviation

units on a scale

Week 0 and Week 12

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Primary

IRLS Rating Scale Total Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)

Posted

Mean

Standard Deviation

units on a scale

DBT WD (up to Week 12)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received immediate-release (IR) tablets of ropinirole once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 milligram (mg)/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed Clinical Global Impression - Improvement [CGI-I]) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

Johns Hopkins RLSQOL Questionnaire Overall Life Impact Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)

FAS. Participants with missing DBT WD data were not included in the analysis.

Posted

Mean

Standard Deviation

units on a scale

DBT WD (up to Week 12)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

Johns Hopkins RLSQOL Questionnaire Overall Life Impact Score for Participants Who Withdrew in the Long-term Treatment Period (LONG WD)

FAS. Participants with no measurement data in the long-term treatment period because of their premature withdrawal without receiving the IP in that period were not included in the analysis.

Posted

Mean

Standard Deviation

units on a scale

LONG WD (up to Week 64)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

The Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 0 and Week 12

The PSQI consists of the following 7 domains: sleep quality, duration getting to sleep, sleep duration, sleep adequacy, sleep disturbance, use of sleeping pill, and somnolence. These domains are numerically scored from 0 to 3, with 0 representing the least severe response and 3 representing the most severe response. The PSQI total score is calculated by summing the individual domain scores. The highest possible score is 21, which represents the most disturbances in sleep quality; the lowest possible score is 0, which represents an absence of disturbances in sleep quality.

FAS. Participants withdrawn from the study before Week 12 were not included in the analysis.

Posted

Mean

Standard Deviation

units on a scale

Week 0 and Week 12

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

The PSQI Total Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)

FAS. Participants with missing DBT WD data were not included in this analysis.

Posted

Mean

Standard Deviation

units on a scale

DBT WD (up to Week 12)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

The PSQI Total Score for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)

FAS. Participants with no measurement data in the long-term treatment period because of their premature withdrawal without receiving the IP in that period were not included in the analysis.

Posted

Mean

Standard Deviation

units on a scale

LONG WD (up to Week 64)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

Number of Participants With the Indicated Responses to the Patient Satisfaction Question at Week 0 and Week 12

Participants responded to a question about their satisfaction with the IP on the following 1 to 7 scale: 1 = very much satisfied; 2 = satisfied; 3 = somewhat satisfied; 4 = neither satisfied nor dissatisfied; 5 = somewhat dissatisfied; 6 = dissatisfied; and 7 = very dissatisfied. At Week 0, participants responded to a question about their satisfaction with their prior medications.

FAS. Participants withdrawn from the study before Week 12 were not included in the analysis.

Posted

Number

participants

Week 0 and Week 12

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR

Secondary

Number of Participants With the Indicated Responses to the Patient Satisfaction Question for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)

FAS. Participants with no measurement data in the long-term treatment period because of their premature withdrawal without receiving the IP in that period were not included in the analysis.

Posted

Number

participants

LONG WD (up to Week 64)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Secondary

Number of Participants With the Indicated Responses to the Patient Satisfaction Question for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)

FAS. Participants with missing DBT WD data were not included in the analysis.

Posted

Number

participants

DBT WD (up to Week 12)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001

Secondary

Mean Daily Number of Hours of RLS Symptoms by Timeframe at Week 0 and Week 12

Participants recorded the onset time and total duration of RLS symptoms on their diary cards for 7 days from one week before each visit. Timeframes were defined as follows: daytime, 7:00AM to 4:59PM; evening, 5:00PM to 7:59PM; and nighttime, 8:00PM to 6:59AM.

FAS. Participants without symptoms were not included in the analysis of Week 0 data. Participants without symptoms and participants prematurely withdrawn from the study were not included in the analysis of Week 12 data.

Posted

Mean

Standard Deviation

hours

Week 0 and Week 12

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR

Secondary

Mean Daily Number of Hours of RLS Symptoms by Timeframe for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)

FAS. Only participants with symptoms who were able to record them in the diary card were included in the analyses of the DBT WD data.

Posted

Mean

Standard Deviation

hours

DBT WD (up to Week 12)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR

Secondary

Mean Daily Number of Hours of RLS Symptoms by Timeframe for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)

FAS. Only participants with symptoms who were able to record them in the diary card were included in the analyses of the and LONG WD data.

Posted

Mean

Standard Deviation

hours

LONG WD (up to Week 64)

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
OG001	Placebo-Ropinirole IR

Secondary

Drug Clearance Rate On-Dialysis and Off-Dialysis During the Maintenance Dose Treatment Phase (in the Long-term Treatment Period)

For on-dialysis analysis, measurements were to have been taken 1 hour before dialysis, in the artery/vein at the beginning, during, and end of dialysis, and 1 hour after dialysis. For off-dialysis analysis, measurements were to have been taken 1 hour before dialysis, at the beginning, during, and end of dialysis, and 1 hour after dialysis.

PK analysis was not performed because there were no participants (who had received a maintenance dose of the IP for more than 1 week in the long-term treatment period) from whom a blood sample could be collected when decision of study termination was made.

Posted

Week 12 through Week 64

ID	Title	Description
OG000	Ropinirole IR-Ropinirole IR	Participants received immediate-release (IR) tablets of ropinirole once daily for 12 weeks in the double-blind treatment period. The dose of investigational product (IP) was upward titrated from 0.25 milligrams (mg)/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed Clinical Global Impression-Improvement [CGI-I]) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0009 affected22 at risk EG0016 affected12 at risk
Gastroenteritis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0002 affected22 at risk EG0010 affected12 at risk
Hordeolum	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected22 at risk EG0011 affected12 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected22 at risk EG0011 affected12 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected22 at risk EG0010 affected12 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected22 at risk EG0010 affected12 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Duodenitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Gastritis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected22 at risk EG0011 affected12 at risk
Hypertension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected22 at risk EG0010 affected12 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected12 at risk
Shunt occlusion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected22 at risk EG0011 affected12 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected22 at risk EG0010 affected12 at risk
Somnolence	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Conjunctivitis	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk

ID	Term
D009422	Nervous System Diseases
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D020447	Parasomnias
D001523	Mental Disorders

ID	Title	Description
BG000	Ropinirole IR-Ropinirole IR	Participants received immediate-release (IR) tablets of ropinirole once daily for 12 weeks in the double-blind treatment period. The dose of investigational product (IP) was upward titrated from 0.25 milligram (mg)/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed Clinical Global Impression - Improvement [CGI-I]) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.
BG001	Placebo-Ropinirole IR	Participants received matching placebo to ropinirole IR in the double-blind treatment period. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants received ropinirole IR tablets in the same way as in the ropinirole IR-ropinirole IR group.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ropinirole IR-Ropinirole IR	Participants received ropinirole IR tablets once daily for 12 weeks in the double-blind treatment period. The dose of IP was upward titrated from 0.25 mg/day to 0.5 mg/day at an interval of at least 1 week, followed by upward titration in increments of 0.5 mg/day at intervals of at least 1 week until sufficient efficacy was obtained (targeting "much improved" or "very much improved" in the investigator/subinvestigator-assessed CGI-I) without a safety/tolerability problem, although the dose did not exceed 3 mg/day. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants were to receive ropinirole IR tablets once daily for 52 weeks with a similar upward titration method as in the double-blind treatment period.			1	22	16	22
EG001	Placebo-Ropinirole IR	Participants received matching placebo to ropinirole IR in the double-blind treatment period. All participants completing the double-blind treatment period were eligible to continue in the open-label long-term treatment period. In the open-label period, participants received ropinirole IR tablets in the same way as in the ropinirole IR-ropinirole IR group.			1	12	10	12

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected22 at risk EG0010 affected12 at risk
Atrial flutter	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected22 at risk EG0011 affected12 at risk