Clinical trial NCT00530790: Clinical Evaluation of Ropinirole CR-RLS ( SK&F101468)Tablets in Restless Legs Syndrome
Official title: Clinical Evaluation of Ropinirole CR-RLS Tablets in Restless Legs Syndrome-Open-Label, Uncontrolled Study. Classification: Clinical Pharmacology, Exploratory
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Restless Legs Syndrome
Keywords: Restless Legs Syndrome
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-09-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was designed to evaluate the safety, pharmacokinetic profile and efficacy in Restless Legs Syndrome patients.


Eligibility criteria: Inclusion Criteria:

* A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:

At Week -1 (at the start of Screening period)

* Patients who are diagnosed with RLS according to the International RLS Study Group's (IRLSSG) Diagnostic Criteria.
* Age: Patients aged at least 18 years and under 80 years.
* Patients who have had RLS symptoms in the evening or nighttime (17:00 to 7:00 next day) for at least 20 days within one month before the start of the screening period. Patients treated for RLS before the start of the Screening period and who do not meet this criterion are considered eligible if the previous therapy can be discontinued from the Screening period.
* Patients who experience RLS symptoms requiring treatment after 17:00 but prior to bedtime.
* Gender: male and female Female of child-bearing potential will be eligible for inclusion in this study. However they must have a negative pregnancy test at the Screening visit. They agree are perform pregnancy test at the time determined and practice one of the following method of contraception from the Screening visit till the end of follow-up examination.

  * Abstinence
  * Oral Contraceptive, either combined or progestogen alone
  * Injectable progestogen
  * Implants of levonorgestrel
  * Estrogenic vaginal ring
  * Percutaneous contraceptive patches
  * 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
* Inpatient or outpatient status: Outpatient status
* Patients who are able to give informed written consent in person. For patients aged under 20 years, their legally acceptable representatives are able to give informed written consent.

At Week 0 (at the start of treatment period)

* Patients who experience RLS symptoms in the evening and nighttime (17:00 to 7:00 next day) for at least 4 days within 7 days before the start of the treatment period.
* Patients who have sleep impairment 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.

Exclusion Criteria:

* Patients requiring treatment for daytime RLS symptoms (7:00 to 17:00).
* Patients with signs of secondary RLS (e.g. chronic renal failure, iron-deficiency anemia, pregnancy, rheumatoid arthritis and Parkinson's disease).
* Patients whose serum ferritin level is \<10 μg/L (ng/mL) at the start of Screening period.
* Patients with following sleep disorder not associated with RLS e.g. narcolepsy, sleep terror disorder, sleep walking disorder, breathing related sleep disorder (Patients with obvious apnea in nighttime sleeping when they do not have alcohol drinking or over 15 times/hour is used to a target for apnea hypopnea index,in which case to implement polysomnography), etc.
* Patients with complication of movement disorder (e.g. Parkinson's disease, dyskinesia, dystonia, etc.).
* Patients with severe hepatic/renal/cardiac/pulmonary disorder or hematopoietic disorder.

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 the medical history or complication of cancer or malignant tumour.
* Patients with the medical history or complication of substance abuse (e.g. alcohol or drug) or dependency of substance for the last one year
* Patients whose diastolic blood pressure (BP) is \>110 mmHg or \<50 mmHg or whose systolic BP is \>180 mmHg or \<90 mmHg at the start of Screening period and Week0.
* Patients intolerant for ropinirole hydrochloride (HCl) or other dopamine agonists.
* Patients with the medical history of allergy to ropinirole HCl in the past.
* Patients with the medical history of Augmentation to ropinirole HCl or other dopamine agonists in the past and those who have experienced early morning RLS symptoms.

Augmentation is defined as below:

RLS appear 2 hours earlier than the pre-treatment. Symptoms become severer than the pre-treatment. Symptoms which start after less time at rest than they did before treatment. The RLS extend to other sites (e.g. arm and trunk).

* Patients without nighttime 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 screening period.
* Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study .
* Patients with chronic hepatitis typeB and /or typeC which is positive of hepatitis B surface antigen （HBsAg）and/or hepatitis C antibody.
* Patients who have medical conditions which, in the opinion of investigator could affect efficacy and safety assessment. This may include, but are not limited to the following disorders: diabetes, peripheral neuropathy, fibromyalgia syndrome, symptomatic orthostatic hypotension, hepatic or renal failure, pleuro-pulmonary fibrosis.
* Patients who have received treatment of an estrogen drug product and a drug that are known to substantially inhibit CYP1A2 and have changed the dose from baseline visit to Week 0.
* Others whom the investigator (sub investigator) considers ineligible for the study.

Primary outcomes:
measure: Drug Related Adverse Events-On-Therapy
timeFrame: Weeks 1 - 12 Treatment Period
measure: Haematology Clinical Lab Values Change From Baseline
timeFrame: Baseline - Week 13 (Follow-up)
measure: Blood Chemistry Clinical Lab Values Change From Baseline
timeFrame: Baseline - Week 13 (Follow-up)
measure: Urinalysis Clinical Lab Values
timeFrame: Baseline - Week 13 (Follow-up)
measure: 12-Lead Electrocardiogram (ECG) Findings Transitions From Baseline
timeFrame: Baseline, Week 4, 8, 12, 13 (Follow-up)
measure: Vital Signs and Body Weight Change From Baseline
timeFrame: Baseline to Week 12/EW
Secondary outcomes:
measure: Change From Baseline to Week 12 in International Restless Leg Syndrome (IRLS) Rating Scale Total Score
timeFrame: Baseline and after Week 12
measure: Clinical Global Impression Scale - Severity of Illness (CGI-S)
timeFrame: Baseline - Final assessment point
measure: Clinical Global Impression Global Improvement (CGI-GI)
timeFrame: Baseline - Final assessment point
measure: Change From Baseline at Week 12/Early Withdrawal (EW) in Pittsburgh Sleep Quality Index (PSQI) Total Score
timeFrame: Baseline - Week 12/EW
measure: Change From Baseline to Week 12/EW in Pittsburgh Sleep Quality Index (PSQI) Total Score by Domains
timeFrame: Baseline - Week 12/EW
measure: Change From Baseline at Week 12/Early Withdrawal (EW) in Johns Hopkins Restless Leg Syndrome Quality of Life Questionnaire (RLSQOL) on the Overall Life Impact Score
timeFrame: Baseline and Week 12/EW
measure: Change From Baseline at Week 12/Early Withdrawal (EW) in Profile of Mood Status (POMS)
timeFrame: Baseline and Week 12/EW
measure: Change From Baseline at Week 12/Early Withdrawal (EW) in Hospital Anxiety and Depression Scale (HADS)
timeFrame: Baseline - Week 12/EW
measure: Pharmacokinetic Analysis: Plasma Concentrations of SK&F101468, an Unchanged Form of Ropinirole.
timeFrame: Weeks 1-12
measure: Pharmacokinetic Analysis: Plasma Concentrations of SK&F104557, a Circulating Metabolite of Ropinirole.
timeFrame: Weeks 1 -12
measure: Pharmacokinetic Analysis: Plasma Concentrations of SK&F89124, a Circulating Metabolite of Ropinirole.
timeFrame: Weeks 1-12
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary with a conclusion.