E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10058920 |
E.1.2 | Term | Restless legs syndrome |
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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 |
The primary objective of the current study will be the evaluation of long-term efficacy of a 26-weeks treatment with pramipexole in patients with idiopathic moderate to severe Restless Legs Syndrome in comparison to placebo. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives are to assess the effects on clinical global impressions - global improvement (based on CGI-I responder rate) and on RLS (based on IRLS responder rate) for 26 weeks under pramipexole in comparison to placebo. Further secondary objectives are to investigate the incidence and severity of augmentation and rebound and to assess the effects on patient global impression (based on PGI responder rate), on RLS symptoms (based on the RLS-6 scales), on associated mood disturbance (based on item 10 of the IRLS), on pain in limbs (based on a visual analogue scale), on quality of life in RLS (based on Johns Hopkins RLS-QoL), on general quality of life (SF-36) and on safety (based on AE profile) of pramipexole in comparison to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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 2. Male or female out-patients aged 18-85 years 3. Diagnosis of idiopathic RLS according to the clinical RLS criteria of the IRLSSG [P03-03355]. 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). 4. RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2) 5. IRLS total score >15 at baseline (Visit 2)
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E.4 | Principal exclusion criteria |
1. Women of child-bearing potential (i.e. premenopausal women, or postmenopausal women less than 6 months after last menses) who do not use during the clinical trial an adequate method of contraception such as: double barrier protection (e.g. diaphragm or condom and spermicide), intrauterine device, hormonal therapy (oral, injectable, or subcutaneous), or partner’s surgical sterilization 2. Any woman of child-bearing potential not having a negative pregnancy test at screening 3. Breastfeeding women 4. Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets 5. Diagnosis of augmentation under previous pharmacological RLS treatment 6. Concomitant or previous pharmacologic therapy as follows: • Any intake of dopamine agonists within 14 days prior to baseline (Visit 2) • Any intake of levodopa within 14 days prior to baseline (Visit 2) • Unsuccessful prior treatment with non-ergot dopamine agonists (e.g. pramipexole, ropinirole) 7. 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, hypnotics, any benzodiazepines, antiepileptics, opioids, ferrous salts. 8. Withdrawal symptoms of any medication present at baseline (Visit 2) 9. Patients receiving antidepressants with any known changes and instabilities in this medication during the last 4 weeks before baseline (Visit 2). (Patients receiving antidepressants for any indication can only be included in the trial if dose and type of antidepressant medication has been unchanged and stable for at least 4 weeks before baseline and is planned to stay unchanged and stable throughout the trial.) 10. History of (during the last 2 years before baseline)/ or presence of a major depressive or bipolar disorder or any psychotic disorder, mental disorders or any present Axis I psychiatric disorder according to DSM IV requiring any therapy 11. History of/or clinical signs of suicidal behaviour, suicide ideation or acute suicidal tendency according to the investigator’s opinion 12. Clinically significant renal disease or calculated creatinine clearance (CrCl) lower than 30 mL/minute at screening (calculation according to the formula of Cockcroft&Gault [R96-0690] see 5.2 laboratory tests) 13. Serum ferritin ≤ 30 ng/mL at screening 14. Patients with any other clinically significant abnormalities in laboratory parameters at screening at the investigator’s discretion 15. Presence of a clinically relevant sleep disorder other than RLS-related 16. Diagnosis of diabetic polyneuropathy 17. Diagnosis of Parkinson’s disease or syndrome 18. History of/or presence of malignant melanoma 19. History of/or presence of a clinically relevant ophthalmopathy other than ametropia or presbyopia (e.g. glaucoma, macula degeneration, retinopathy) 20. History of/or presence of alcohol abuse or drug addiction within the last 2 years before screening 21. 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 [R06-2803, R06-2767] and/or in the opinion of the investigator 22. Patients on a shift-work-schedule who are unable to follow a regular sleep-wake cycle enabling use of study medication at times indicated and/or who are unable to comply with the scheduled study visits 23. Participation in an investigational drug study within one month prior to the start of this study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the change from baseline after 26 weeks of treatment in the total score of the International Restless Legs Syndrome Study Group Rating Scale (IRLS) under treatment with pramipexole in comparison to placebo. |
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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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 | Yes |
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
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for the current trial the "end of trial overall" is defined as the last visit completed by the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |