Pramipexole in Out-patients With Idiopathic Restless Legs Syndrome (IRLS)
Condition: Restless Legs Syndrome
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Intervention: Pramipexole; Placebo
Intervention MeSH terms: Pramipexole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 306.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      To determine efficacy and safety of Pramipexole 0.125mg to 0.75mg daily for 6 weeks compared
      to placebo in the treatment of idiopathic Restless Legs Syndrome (RLS)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent consistent with International Conference on Harmonisation
             (ICH) / Good Clinical Practice (GCP) and local legislation given prior to any study
             procedures.

          2. Ability and willingness to comply with study treatment regimen and to attend study
             assessments.

          3. Male or female out-patients aged 18-80 years.

          4. Diagnosis of idiopathic Restless Legs Syndrome (IRLS) according to the clinical
             Restless Legs Syndrome (RLS) criteria of the International Restless Legs Syndrome
             Study Group (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).

          5. Restless Legs Syndrome (RLS)rating scale for severity total score >15.

          6. Restless Legs Syndrome (RLS) symptoms present at least 2 to 3 days per week during the
             last 3 months.

        Exclusion Criteria:

          1. Women of child-bearing potential (i.e. premenopausal women, or postmenopausal women
             less than 2 years after last menses) who do not use during the clinical trial an
             adequate method of contraception such as: hormonal therapy (combined oral
             contraceptives, injectables, or subcutaneous implants), hormonal intrauterine devices,
             sexual abstinence, surgical sterilization of patient and/or partner, hysterectomy,
             bilateral ovariectomy or partners vasectomy

          2. Any woman of child-bearing potential not having a negative pregnancy test at screening

          3. Patients who are breastfeeding

          4. Concomitant or previous pharmacologically therapy of RLS as follows:

               -  Any intake of levodopa within 5 days prior to baseline visit (V2)

               -  Any intake of dopamine agonists within 14 days prior to baseline visit (V2)

          5. Current (less than 14 days before treatment with trial medication or concomitant)
             treatment with medication or dietary supplements, which could significantly influence
             RLS symptoms, e.g. dopaminergic (other than levodopa or dopamine agonists) or
             anti-dopaminergic drugs, non-selective Monoamine Oxidase (MAO) inhibitors,
             sympathomimetics, neuroleptics, anti-depressants, hypnotics, any benzodiazepines,
             antiepileptics, opioids, clonidine, magnesium, ferrous salts, Folic acid, vitamin B12,
             antihistaminics, lithium, metoclopramide or Withdrawal symptoms caused by stopping any
             of the drugs above

          6. Confirmed diagnose of diabetic nephropathy or clinically significant renal disease

          7. Creatinine higher than upper limit of normal (ULN) at screening

          8. Clinical significant hepatic disease or Alanine aminotransferase (ALT) >2 times the
             upper limit of normal range at screening

          9. Clinical or laboratory signs of microcytic anaemia, or ferritin in serum below the
             lower bound of the reference range

         10. Any of the following lab results at screening:

               -  Basal Thyroid Stimulating Hormone (TSH), T3 or T4 clinically significantly (at
                  the investigators discretion) out of normal range at screening (if not caused by
                  substitution therapy according the investigators opinion)

               -  Patients with any clinically significant abnormalities in laboratory parameters
                  at screening at the investigators discretion

         11. Other clinically significant metabolic-endocrine, haematological, gastro-intestinal
             disease or pulmonary disease (such as severe COPD). Poorly controlled cardiovascular
             disease (including hypotension and severe coronary artery disease)

         12. History or clinical signs of peripheral neuropathy (PNP) of any origin in physical,
             neuro-logical examination, myelopathy or multiple sclerosis or any other neurological
             disease, with potential to secondarily cause RLS symptoms

         13. Presence of any other sleep disorder, such as, Rapid Eye Movement (REM) sleep
             behaviour disorder, narcolepsy or sleep apnoea syndrome

         14. History of Schizophrenia or any psychotic disorder, history of mental disorders due to
             a general medical condition or any present axis I psychiatric disorder according to
             Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM IV)
             requiring any medical therapy

         15. History of alcohol abuse or drug addiction within the last 2 years before screening

         16. Participation in a drug study within two months prior to the start of this study

         17. History of or clinical signs for any form of epilepsy or seizures apart from fever
             related seizures in early childhood

         18. History of or clinical signs of malign neoplasm

         19. 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

         20. Any other conditions that in the opinion of the investigator would interfere with the
             evaluation of the results or constitute a health hazard for the subject