Idiopathic and Uremic Restless Legs Syndrome (RLS) MedDRA version: 7.0 Level: LLT Classification code 10058920
Conditions
Interventions
Product Name: Lisuride
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: Lisuride
CAS Number: 18016-80-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2
Sponsors
NeuroBiotec GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: Patient is informed and given ample time and opportunity to think about participation in the study and has given written informed consent. 2. Presence of RLS: Idiopathic or uremic restless legs syndrome. Uremic patients must un-dergo at least two, usually three hemodialyses per week. Patients with peritoneal dialysis are not to be enrolled. 3. Previous treatment: - Previously untreated for RLS (de novo patients) or - Patients dissatisfied with any preceding therapy, who had responded at least initially to previous dopaminergic therapy, and - for whom a dopaminergic therapy with Lisuride or Ropinirole is indicated. 4. Gender: Males and females. 5. Age: Males and females aged between 18 and 80 years (boundaries included). 6. BMI: Body Mass Index (BMI) = 18.0 and ? 35.0 (body mass in kg divided by (body height in meter) 2). 7. Patient’s capability: Patient is capable - of accurately filling out evaluation forms after being trained (sufficient knowledge of German language required). - to apply and remove the trial patch correctly and consistently. 8. Patient’s compliance: Readiness and ability on the part of the patient to comply with the physician's instructions and to follow the scheduled visits. Patient understands the investi-gational nature of the trial and is willing to accept that he/she might be treated with pla-cebo during the treatment period. 9. Pregnancy: Women of child-bearing potential must use a reliable method of contracep-tion if not sexually abstinent, although there is no evidence of an adverse teratogenic effect of Lisuride or Ropinirole on pregnancies. Negative pregnancy test at baseline in females of childbearing potential is mandatory. Lack of childbearing potential is defined as post-menopause (at least two years after last menstruation) or surgical sterilization or hysterec-tomy at least three months before study start). In addition, the patients must comply with the following criteria at the baseline Visit 2: 10. Four RLS diagnostic criteria: Presence of all four clinical manifestations of RLS (ac-cording to the revised version of the RLS diagnostic criteria (Allen et al., 2003)) 1) an urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. (Sometimes the urge to move is present without the uncomfortable sensations and sometimes the arms or other body parts are involved in addition to the legs.) 2) the urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting. 3) the urge to move or unpleasant sensations are partially or totally relieved by move- ment, such as walking or stretching, at least as long as the activity continues. 4) the urge to move or unpleasant sensations are worse in the evening or night than dur- ing the day or only occur in the evening or night. (When symptoms are very severe the worsening at night may not be noticeable but must have been previously present.) 11. RLS-Diagnosis: Highly probable diagnosis of RLS (score > 10) according to the “Rest-less Legs Syndrome Diagnostic Index” (RLS-DI, see Appendix 2). In addition, at least one of the criteria 7 “positive family history of the RLS”, 8 “positive response to dopaminergic treatment”, 9 “objective findings of periodic limb movements in polysomnography or ac-tigraphy”, or 10 “usual findings in neurological examination” must be definitely present. 12. IRLS score: ? 15
Exclusion criteria
Exclusion criteria: In detail, patients are to be excluded from the study, if they display any of the following crite-ria upon enrolment (Screening Visit 1): 1. Secondary RLS: - RLS due to, e.g. iron deficiency anemia, rheumatoid arthritis; however, patients with secondary RLS due to renal insufficiency (uremia) are allowed to participate in this study. - RLS associated with previous or concomitant therapy with dopamine D2 receptor an-tagonists, butyrophenones, metoclopramide, atypical antipsychotics (e.g. olanzapine), tri- and tetracyclic antidepressants, mianserine, lithium or H2-blockers (e.g. cimet-idine), or due to withdrawal from drugs such as anticonvulsants, benzodiazepines, bar-biturates, and other hypnotics. 2. Sleep disorders: History or presence of sleep disturbances caused by sleep apnea syn-drome (sleep apnea index at local sleep laboratory > 20 / h for exclusion, if available), narcolepsy, myoclonus epilepsy either observed during polysomnography or explored in patient history 3. Concomitant central nervous system diseases: Additional clinically relevant concomi-tant neurological diseases like: - Polyneuropathy, akathisia, claudication, painful legs and moving toes, radiculopathy, or attention deficit hyperactivity disorder whose symptoms could overlap those of RLS. - Dementia (e.g. Alzheimer’s disease), progressive supranuclear paresis, multisystem at-rophy, Huntington’s Chorea, amyotrophic lateral sclerosis, Isaac’s syndrome, Stiff-Man syndrome, or Gilles de la Tourette’s syndrome. - History or presence of hallucinating or psychotic episodes which had needed treatment (including schizophrenia). - History of chronic alcohol or drug abuse within the last 12 months. 4. Other concomitant medical conditions: Any medical or psychiatric condition, which in the opinion of the investigator can jeopardize or would compromise the patient’s ability to participate in this trial or confound interpretation of the data, excludes a patient from par-ticipation in this study. Especially, the following are excluded: - Any severe acute disease within the last 4 weeks prior to the first study drug admini-stration. - Clinically relevant cardiac dysfunction and/or arrhythmias (e.g. suspected conduction system dysregulations, second or third degree AV block, complete left or right bundle branch block, sick-sinus-syndrome, New York Heart Association Class III or IV con-gestive heart failure, myocardial infarction within 12 months prior to Screening Visit 1) - Fibromyositis, severe chronic lung disease, insulin-dependent diabetes mellitus, leu-kemia, anemia, or primary amyloidosis. - Malignant neoplastic disease requiring therapy within 12 months prior to the Screening Visit 1. - Clinically relevant venous or arterial peripheral vascular disease. 5. Abnormal findings in laboratory values: The following findings will exclude a patient from participation in the trial: - Clinically significant liver failure (total bilirubin > 2.0 mg/dl or SGOT and/or SGPT greater than two times the upper limit of the reference range). - Clinically relevant renal dysfunction (serum creatinine > 2.0 mg/dl). - Clinically relevant presence of iron deficiency (as a rule is indicated by measures of ferritine below the lower boundary of the central laboratory). In such a case the patient is a screening failure and has to be discontinued from study. However, if after iron substitution serum ferritine will have normalized, patients can be enrolled again and re-evaluated for eligibility. 6
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (1) The first primary study objective is to investigate the superior efficacy of an optimized individual dose of transdermal Lisuride (dose range: 2.5 to 7.5 mg every second day, patch sizes: 10 cm2 to 30cm2) with placebo after 12 weeks. (2) The second primary study objective is to investigate the superior efficacy of an optimized individual dose of transdermal Lisuride (dose range: 2.5 to 7.5 mg every second day, patch sizes: 10 cm2 to 30cm2) with an individu-ally optimized dose of oral Ropinirole (dose range: 1.0 mg to 3.0 mg / day) after 12 weeks. (3) The third primary study objective is to investigate the superior efficacy of an optimized individual dose of Ropinirole (dose range: 1.0 to 3.0 mg / day) compared to placebo after 12 weeks. Changes in the IRLS total score are used as primary efficacy outcome measure. ;Secondary Objective: The secondary study objectives are: (1) to evaluate further efficacy criteria, quality of life, tolerability and safety of Lisuride TTS patch treatment in comparison to placebo and Ropinirole af-ter 12 weeks of double-blind treatment; (2) to evaluate further efficacy criteria, quality of life, tolerability and safety of Ropinirole in comparison to placebo after 12 weeks of double-blind treat-ment; (3) to evaluate long-term efficacy, quality of life, tolerability and safety of Lisuride TTS patch treatment after open-label treatment between week 13 and week 48. ;Primary end point(s): Primary efficacy variable: International RLS Study Group Rating Scale (IRLS): Absolute change in the IRLS sum score from baseline (Visit 2) to Visit 7. Hierarchy of comparisons: 1) Lisuride versus Placebo 2) Lisuride versus Ropinirole 3) Ropinirole versus Placebo | — |
Countries
Austria
Outcome results
None listed