Long-Term Safety Of Ropinirole XR In Patients With Restless Legs Syndrome

Condition(s) targeted: Restless Legs Syndrome

Intervention: Ropinirole Extended Release (XR) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, MD, Study Director, Affiliation: GlaxoSmithKline

The primary objective of this study is to assess the safety and tolerability of ropinirole XR in the long-term treatment (up to 52 weeks)of adults with RLS.

Official title: A 52-Week, Open-Label Study to Assess the Long-Term Safety of Ropinirole Extended Release (XR) in Patients With Restless Legs Syndrome (RLS)

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Incidence/severity of adverse events Changes in vital signs Labs ECG Assessment of augmentation and rebound (worsening of RLS symptoms).

Secondary outcome:

Change from baseline in IRLS Rating Scale total score CGI Scale scores Medical Outcomes Study Sleep Scale scores Other subject-reported health outcomes.

Incidence and severity of adverse events.

Changes in vital signs (blood pressure and pulse) and weight.

Changes in laboratory assessments (hematology and clinical chemistry).

Changes in electrocardiogram (ECG) parameters.

Assessment of augmentation.

Assessment of rebound.

Change from baseline in the IRLS Rating Scale total score at Week 52 LOCF (last observation carried forward).

Proportion of subjects with a score of much improved (2) or very much improved (1) on CGI-I at Week 52 LOCF.

CGI Severity of Illness (CGI-S) at Week 52 LOCF.

Change from baseline in the domains of the Medical Outcomes Study (MOS-12) Sleep Scale at Week 52 LOCF.

Change from baseline in the overall life impact score of the RLS Quality of Life Questionnaire at Week 52 LOCF.

Change from baseline in the anxiety and depression domains of the Hospital Anxiety and Depression (HADS) Scale at Week 52 LOCF.

Change from baseline in the total score and domains of the Profile of Mood States (POMS) Scale Short Form at Week 52 LOCF.

Change from baseline in the parameters for the work Productivity and Activity Impairment - Specific Health Problem (WPAI-SHP) Questionnaire at Week 52 LOCF.

Proportion of subjects satisfied with their treatment at Week 52 LOCF.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion criteria:

- A subject will be eligible for inclusion in this study only if all of the following

criteria apply:

- Subjects in North America ≥18 years of age who

1. Have successfully completed one of the following parent studies: 101468/205, ROX104805; OR

2. Have a diagnosis of primary RLS using the International RLS Study Group (IRSSG) Diagnostic Criteria (Appendix 10), experience RLS symptoms during both the evening (before 8 PM) and night-time, and have a total score ≥15 on the IRLS Rating Scale at Baseline. Subjects must have a history of a minimum of 20 evenings/nights of RLS episodes per month (e. g., any combination of evenings and/or nights for ≥ 20 days). During Screening/Washout, RLS symptoms must be present for at least 4 of 7 evenings/nights immediately prior to the Baseline Visit (e. g., any combination of evenings and/or nights for ≥ 4 days).

- Subjects must give written informed consent prior to any specific study procedures.

Exclusion Criteria:

- Subjects who have any medical conditions which, in the opinion of the investigator,

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.

- Subjects having clinically significant abnormal laboratory or ECG findings not

resolved at time of baseline examinations. 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 augmentation and/or end-of-dose rebound symptoms.

- Augmentation is defined as 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, or symptoms which involve other parts of the body, such as the arms or trunk.

- End-of-dose rebound is defined as a re-emergence of RLS symptoms in the early

morning the day after taking the dose of RLS medication.

- Subjects who have exhibited intolerance to ropinirole.

- For subjects entering Study 206, certain medications must be discontinued prior to

entering the study. The following medications are prohibited for the duration of the study period which is up to and including the Follow-up visit:

·dopamine agonists (including ropinirole immediate release formulation), dopamine antagonists (e. g., typical neuroleptics, metoclopramide), levodopa/carbidopa The minimum discontinuation period is generally 5 half-lives or 7 consecutive evening/nights medication-free, prior to baseline, whichever is the longer period. If the subject will require longer than 2 weeks following the Follow-up visit of the parent study to complete the washout, GSK must be consulted for further instructions.

- Other medications, including those with partial dopaminergic activity (e. g., atypical

antipsychotics, certain antidepressants such as bupropion, tricyclic antidepressants and monoamine oxidase inhibitors) may have additive activity with ropinirole and should be used with caution in patients taking ropinirole. For patients on stable doses, these agents may be permitted; however, it is recommended that the dose of the medication remain stable throughout the duration 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.

- Women who have a positive pregnancy test.

- Women of child-bearing potential who are not practicing a clinically accepted method

of contraception such as oral contraception, surgical sterilization, IUD, diaphragm in conjunction with spermicidal foam and condom on the male partner, or systemic contraception (e. g. Norplant).

The following exclusion criteria must be assessed at Study 206 Screen/Baseline for subjects who are not rolling in following completion of Study 101468/205 or ROX104805:

- 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).

- Signs of secondary RLS (e. g., end stage renal disease, iron deficient anemia or

pregnancy at Baseline Visit)

- Subjects requiring treatment of daytime RLS symptoms (daytime defined as 7: 00 AM until

5: 00 PM).

- Subjects with a history of alcohol or substance abuse within the past year.

- Subjects who, in the opinion of the investigator, would be non-compliant with the

visit schedule or other study procedures

- Participation in any clinical drug or device trial (other than Study 101468/205 or

ROX104805) in the one month prior to the Baseline Visit

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Starting date: September 2005
Ending date: October 2007
Last updated: February 27, 2008