Clinical trial NCT00996944: Clinical Evaluation of Ropinirole IR (Immediate Release) Tablets in Patients Who Are Diagnosed With Symptomatic Restless Legs Syndrome (RLS) Associated With Chronic Kidney Disease (CKD) Managed With Haemodialysis (Including Haemofiltration and Haemodiafiltration)
Official title: Clinical Evaluation of Ropinirole IR (Immediate Release) Tablets in Patients Who Are Diagnosed With Symptomatic Restless Legs Syndrome (RLS) Associated With Chronic Kidney Disease (CKD) Managed With Haemodialysis (Including Haemofiltration and Haemodiafiltration)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Restless Legs Syndrome
Keywords: ropinirole
haemodialysis
restless legs syndrome
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, placebo controlled, parallel group, double-blind, randomized comparison study to evaluate the efficacy and safety of ropinirole IR tablets orally administered for 12 weeks in patients with symptomatic restless legs syndrome associated with Chronic kidney disease (CKD) managed with haemodialysis (including haemofiltration and haemodiafiltration) (hereinafter referred to as "uRLS"), to evaluate the efficacy and safety of long-term administration of ropinirole IR tablets, and assess the effect on the steady state pharmacokinetics in the long-term administration period of ropinirole IR tablets.


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.

Primary outcomes:
measure: International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 0 and Week 12
timeFrame: Week 0 and Week 12
measure: IRLS Rating Scale Total Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)
timeFrame: DBT WD (up to Week 12)
Secondary outcomes:
measure: IRLS Rating Scale Total Score for Participants Who Withdrew in the Long-term Treatment Period (LONG WD)
timeFrame: LONG WD (up to Week 64)
measure: Number of Participants With the Indicated Clinical Global Impression-Improvement (CGI-I) Scores at Week 12
timeFrame: Week 12
measure: Number of Participants With the Indicated CGI-I Scores for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)
timeFrame: DBT WD (up to Week 12)
measure: Number of Participants With the Indicated CGI-I Scores for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)
timeFrame: LONG WD (up to Week 64)
measure: Johns Hopkins Restless Legs Syndrome Quality of Life (RLSQOL) Questionnaire Overall Life Impact Score at Week 0 and Week 12
timeFrame: Week 0 and Week 12
measure: Johns Hopkins RLSQOL Questionnaire Overall Life Impact Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)
timeFrame: DBT WD (up to Week 12)
measure: Johns Hopkins RLSQOL Questionnaire Overall Life Impact Score for Participants Who Withdrew in the Long-term Treatment Period (LONG WD)
timeFrame: LONG WD (up to Week 64)
measure: The Pittsburgh Sleep Quality Index (PSQI) Total Score at Week 0 and Week 12
timeFrame: Week 0 and Week 12
measure: The PSQI Total Score for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)
timeFrame: DBT WD (up to Week 12)
measure: The PSQI Total Score for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)
timeFrame: LONG WD (up to Week 64)
measure: Number of Participants With the Indicated Responses to the Patient Satisfaction Question at Week 0 and Week 12
timeFrame: Week 0 and Week 12
measure: Number of Participants With the Indicated Responses to the Patient Satisfaction Question for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)
timeFrame: LONG WD (up to Week 64)
measure: Number of Participants With the Indicated Responses to the Patient Satisfaction Question for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)
timeFrame: DBT WD (up to Week 12)
measure: Mean Daily Number of Hours of RLS Symptoms by Timeframe at Week 0 and Week 12
timeFrame: Week 0 and Week 12
measure: Mean Daily Number of Hours of RLS Symptoms by Timeframe for Participants Who Withdrew From the Double-Blind Treatment Period (DBT WD)
timeFrame: DBT WD (up to Week 12)
measure: Mean Daily Number of Hours of RLS Symptoms by Timeframe for Participants Who Withdrew fn the Long-term Treatment Period (LONG WD)
timeFrame: LONG WD (up to Week 64)
measure: Drug Clearance Rate On-Dialysis and Off-Dialysis During the Maintenance Dose Treatment Phase (in the Long-term Treatment Period)
timeFrame: Week 12 through Week 64
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokushima
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: This study has not been published in the scientific literature.