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)

NCT00996944 | Terminated Phase 2 Results

• 1 other identifier: 113079
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 19

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.

Conditions

Restless Legs Syndrome

Keywords

ropinirole; haemodialysis; restless legs syndrome

Outcome Measures

Primary Outcomes (2)

• 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 A total of 17 participants were prematurely withdrawn from the study before Week 12.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 A total of 17 participants were prematurely withdrawn from the study before Week 12, and 2 participants had missing DBT WD data.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 (17)

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

  LONG WD (up to Week 64)

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

  Week 12

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

  DBT WD (up to Week 12)

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

  LONG WD (up to Week 64)

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

  Week 0 and Week 12

Study Arms (2)

Ropinirole IR

EXPERIMENTAL

Drug: Ropinirole immediate release (IR)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

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.

Ropinirole IR

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[Kurokawa, 2002\].

You may not qualify if:

• 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (19)

GSK Investigational Site

Aichi, 440-0035, Japan

Location

GSK Investigational Site

Aichi, 453-8566, Japan

Location

GSK Investigational Site

Chiba, 277-0084, Japan

Location

GSK Investigational Site

Chiba, 289-2511, Japan

Location

GSK Investigational Site

Fukuoka, 803-0844, Japan

Location

GSK Investigational Site

Hiroshima, 737-0131, Japan

Location

GSK Investigational Site

Hokkaido, 070-0030, Japan

Location

GSK Investigational Site

Hyōgo, 670-0947, Japan

Location

GSK Investigational Site

Ibaraki, 300-0053, Japan

Location

GSK Investigational Site

Ibaraki, 302-0022, Japan

Location

GSK Investigational Site

Kagawa, 761-8024, Japan

Location

GSK Investigational Site

Miyagi, 981-0911, Japan

Location

GSK Investigational Site

Nagano, 392-8510, Japan

Location

GSK Investigational Site

Nagasaki, 850-0052, Japan

Location

GSK Investigational Site

Okinawa, 901-2132, Japan

Location

GSK Investigational Site

Okinawa, 904-2143, Japan

Location

GSK Investigational Site

Osaka, 547-0024, Japan

Location

GSK Investigational Site

Shizuoka, 424-0012, Japan

Location

GSK Investigational Site

Tokushima, 770-0011, Japan

Location

Related Publications (1)

• This study has not been published in the scientific literature.

  BACKGROUND

Related Links

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

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

ropinirole

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 16, 2009
• Study Start: November 30, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 29, 2010
• Last Updated: August 10, 2018
• Results First Posted: June 13, 2011

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (19)