E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Restless Legs Syndrome, RLS |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058920 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to determine the efficacy of pramipexole 0.125 mg to 0.75 mg daily versus placebo on RLS symptoms based on the IRLS scale and on associated mood disturbances based on IRLS item 10 and depressive symptoms based on the Beck Depression Inventory BDI-II , each defined as change from baseline Visit 2 after 12 weeks of treatment Visit 8 |
|
E.2.2 | Secondary objectives of the trial |
the assessment of the effects on clinical global impressions-global improvement CGI-I responder rate , RLS IRLS responder rate , depressive symptoms BDI-II responder rate , pain in limbs VAS , sleep quality and severity of RLS symptoms RLS-6 , anxiety HADS-A , quality of life in RLS Johns Hopkins RLS QoL questionnaire , patient global impression PGI and safety AE profile each defined as change from baseline in comparison to placebo |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
-Written informed consent consistent with ICH-GCP and local IRB/IEC requirements obtained prior to any study procedures being performed and the ability and willingness to comply with study treatment regimen and to attend study assessments.-Male or female out-patients aged 18-80 years. -Diagnosis of idiopathic RLS according to the clinical RLS criteria of the IRLSSG. All four criteria must be present to fulfil the diagnosis of RLS 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 . The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting. The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues. The urge to move or unpleasant sensations are worse in the evening or night than during 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 .-RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline Visit 2 .-In addition all of the following must be demonstrated at Visit 2 baseline IRLS total score 15. A score of 2 for item 10 of the IRLS rating scale. |
|
E.4 | Principal exclusion criteria |
-Women of child-bearing potential who do not use, during the clinical trial an adequate method of contraception e.g. mechanical and pharmacological therapy , or partner s surgical sterilization. -Any women of child-bearing potential not having negative pregnancy test at screening. -Breastfeeding women. -Concomitant or previous pharmacologic therapy for RLS as follows Any intake of dopamine agonists and levodopa within 14 days prior to baseline Visit 2 Any intake of levodopa prior to baseline visit, if augmentation in RLS symptoms was observed Unsuccessful prior treatment with non-ergot dopamine agonists e.g. pramipexole, ropinirole Any intake of antidepressants last 6 weeks prior to baseline Visit 2 ; interruption of indicated anti-depressive treatment due to study reasons is not allowed. -All treatment less than 14 days before baseline Visit 2 or concomitant treatment with medication or dietary supplements, which could significantly influence RLS symptoms, e.g. dopaminergic other than levodopa and dopamine agonists or antidopaminergic drugs, non-selective MAO inhibitors, sympathomimetics, neuroleptics, antidepressants, hypnotics, any benzodiazepines, antiepileptics, opioids, clonidine, ferrous salts, magnesium, folic acid, vitamin B12, antihistaminics, lithium, metoclopramide. -Withdrawal symptoms of any medication must not be present at baseline Visit 2 . -Previous pramipexole non-responders in other indications than RLS. -Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets. -Diagnosis of diabetes mellitus requiring insulin therapy. -Any of the following laboratory results at screening Patients with any clinically significant abnormalities in laboratory parameters at screening at the investigator s discretion Haemoglobin Hb below lower limit of normal LLN -Clinically significant renal disease or calculated creatinine clearance CrCl lower than 30 mL/minute at screening. -Clinically significant hepatic disease or GPT 2 times the upper limit of normal ULN at screening. -Serum ferritin 10 ng/mL at screening. -History of/or malignant melanoma. -History of/or clinically significant vision abnormalities. -History of/or any other sleep disorder other than RLS-related , such as Rapid Eye Movement REM sleep disorder, narcolepsy or sleep apnoea syndrome. -History of/or major depressive disorder or any psychotic disorder, mental disorders or any present Axis I psychiatric disorder according to DSM IV requiring any medical therapy, or BDI-II total score 28. -History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigator s opinion e.g. BDI-II item 2 score 2, or item 9 score 0 . -History of/or alcohol abuse or drug addiction within the last 2 years before screening. -Patients on a shift-work-schedule or who are otherwise unable to follow a regular sleep-wake cycle enabling use of study medication at times indicated. -Participation in an investigational drug study within one month prior to the start of this study. -Patients with any clinically significant conditions that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health hazard for the patient according to SPC SPC Sifrol . |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline after 12 weeks of treatment in IRLS total score, IRLS item 10 score and BDI-II total score. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |