Restless Legs Syndrome MedDRA version: 13.1 Level: PT Classification code 10058920 Term: Restless legs syndrome System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Targinact 5 mg/2.5 mg prolonged-release tablets
Product Name: oxycodone/naloxone prolonged release tablets 5/2.5 mg
Product Code: OXN PR 5/2.5 mg
Pharmaceutical Form: Prolonged-release tab
Sponsors
Mundipharma Research GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects at least 18 years or older. 2. Female subjects less than one year post-menopausal must have a negative pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilization, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasoectomised partner. 3. Diagnosis of RLS (score = 11) according to the “Restless Legs Syndrome Diagnostic Index” (RLS-DI, see Appendix 12.10). 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 actigraphy” must be definitely present or criterion 10 “usual findings in neurological examination” is answered with “no” (Benes & Kohnen, 2008). 4. Patients dissatisfied with any current (lack of efficacy or unacceptable tolerability) or previous (those who stopped previous therapy because of non-efficacy or side effects) drug treatment of RLS who would benefit from an alternative treatment option with OXN PR. 5. Presence of RLS symptoms for at least 6 months. 6. IRLS score at screening Visit (visit 1) of = 15. 7. Onset of RLS symptoms during the day usually (on at least 4 days per week) before 18:00. 8. Subjects must not have received opioid containing medication (including tilidine, tramadol, codeine) for the treatment of RLS and other disorders (pain) on a regular basis at any time before enrolment. Occasional use for treatment of cough/cold, pain etc is acceptable if the last intake was at least 1 month before enrolment. 9. Subjects willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent and willing to discontinue their current RLS treatment. 10. Subjects taking pre-study, non-opioid analgesics, that are thought to be stable, and are considered necessary for the subject’s welfare, and are anticipated to remain stable throughout the Double-blind Phase of the study, and are to be continued under the supervision of the investigator, are eligible. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Secondary RLS due to, e.g. iron deficiency anemia, renal insufficiency, rheumatoid arthritis. 2. RLS associated with previous or concomitant therapy with dopamine D2 receptor antagonists, butyrophenones, metoclopramide, atypical antipsychotics (e.g. olanzapine), tri- and tetracyclic antidepressants, mianserine, lithium or H2 3. History or presence of sleep disturbances caused by sleep apnea syndrome, narcolepsy, myoclonus epilepsy either observed during polysomnography or explored in patient history. -blockers (e.g. cimetidine), or due to withdrawal from drugs such as anticonvulsants, benzodiazepines, barbiturates, and other hypnotics. 4. Any disorder whose symptoms could overlap those of RLS (mimics of RLS) according to the table of differential diagnoses (see Appendix 12.15). 5. Subjects with acute, clinical augmentation according to MPI criteria checklist previous treatment (Appendix 12.13) and screening tool for augmentation Visit 1 (Appendix 12.11) as assessed by the investigator. 6. Dementia (e.g. Alzheimer’s disease), progressive supranuclear paresis, multisystem atrophy, Huntington’s Chorea, amyotrophic lateral sclerosis, Isaac’s syndrome, Stiff-Man syndrome, or Gilles de la Tourette’s syndrome. 7. History or presence of hallucinating or psychotic episodes which had needed treatment (including schizophrenia). 8. Prohibited concomitant or prior medication: Use of drugs likely to influence sleep architecture or motor manifestations during sleep or other central nervous system (CNS) depressants are not permitted from last week before randomisation visit (Visit 3) onwards. These include levodopa, dopamine agonists, catechol-O-methyl-transferase (COMT) inhibitors, neuroleptics, hypnotics, anxiolytic drugs, benzodiazepines, antidepressants psychostimulatory drugs and anticonvulsants. Inclusion is possible: If patients are on stable therapy for depression or anxiety disorders with antidepressants (SSRI or NARI) or anxiolytic drugs for at least six months. 9. Subjects presently taking, or who have taken naloxone or naltrexone within 30 days of study entry (defined as the start of the Screening Period). 10. Subjects with any contraindication or any history of hypersensitivity to oxycodone, naloxone, related products or other ingredients (severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, paralytic ileus). 11. Evidence of clinically significant cardiovascular, renal, hepatic, somatisation disorders or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination, that would place the subject at risk upon exposure to the study medication or that may confound the analysis and/or interpretation of the study results. 12. Subjects with evidence of impaired liver/kidney function upon entry into the study defined as aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels > 3 times the upper limit of normal; gamma glutamyl transpeptidase (GGT or GGTP) > 3 times the upper limit of normal; total bilirubin level outside of the reference range; and/or creatinine level outside of the reference range (subjects whose total bilirubin levels or creatinine levels are below the lower limit of normal can participate in the study if they meet the criteria described in section 9.4.4.3), or in the investigator’s opinion, liver and/or kidne
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for the 12-week Titration-/Maintenance Period is: • To demonstrate superior efficacy of OXN PR compared to PLA in the improvement of symptom severity of RLS as measured by the International Restless Legs Syndrome Study Group Rating Scale (IRLS scale). The objectives for the open-label Extension Phase are: • Proportion of subjects with Augmentation according to the MPI Criteria, 2007 (Max Planck Institute Consensus conference) during OXN PR treatment (Expert’s/Investigator’s assessment). • Assessment of severity of augmentation (ASRS) during OXN PR treatment. • Tolerability and safety of long-term treatment with OXN PR. • Long-term efficacy of OXN PR during the open-label Extension Phase in all efficacy variables listed above.;Secondary Objective: Assessment of: • improvement of severity of RLS in the CGI severity scale in patients taking OXN PR compared to PLA • change of severity of RLS during the day at rest (RLS-6-Rating Scale) OXN PR compared to PLA • change of severity of RLS in the further RLS-6-Rating scales OXN PR compared to PLA • change in NRS for pain in patient’s legs or arms (RLS pain) OXN PR compared to PLA • the Responder Rate of subjects with at least 50% improvement in the IRLS scale or ratings “very much” or “much” improved in the CGI scale 2 “change of condition” • the Remitter Rate IRLS scale 0 or a final IRLS score = 10 • change in disease-specific quality of life (QoL-RLS-Scale) • change in sleep behaviour of subjects with OXN PR compared to PLA using the MOS sleep scales • therapeutic effect (based on CGI item 3) • the Incidence of Augmentation • severity of augmentation (ASRS);Primary end point(s): Change in severity of RLS as measured by the IRLS scale total score from end of Maintenance Phase to baseline. ;Timepoint(s) of evaluation of this end point: 14 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Open Label Extension Phase: Proportion of subjects with Augmentation according to the MPI Criteria, 2007 (Max Planck Institute Consensus conference) during OXN PR treatment(Expert’s/Investigator’s assessment). Assessment of severity of augmentation (ASRS) during OXN PR treatment. Tolerability and safety of long-term treatment with OXN PR. Long-term efficacy of OXN PR during the open-label Extension Phase in all efficacy variables listed above. ;Timepoint(s) of evaluation of this end point: 40 weeks | — |
Countries
Austria, Germany, Spain
Outcome results
None listed