Claudia Trenkwalder1, K Ray Chaudhuri2, Pablo Martinez-Martin3, Olivier Rascol4, Reinhard Ehret5, Martin Vališ6, Maria Sátori7, Anna Krygowska-Wajs8, Maria J Marti9, Karen Reimer10, Alexander Oksche11, Mark Lomax12, Julia DeCesare12, Michael Hopp13. 1. Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurosurgery, University Medical Centre, Goettingen, Germany. Electronic address: ctrenkwalder@gmx.de. 2. National Parkinson's Foundation, Parkinson's Centre of Excellence, King's College Hospital, London, UK; Biomedical Research Unit for Dementia, King's College, London, UK. 3. National Centre of Epidemiology, Carlos III Institute of Health, Madrid, Spain. 4. Clinical Investigation Centre 1436, INSERM, Toulouse, France; University Hospital, Toulouse, France. 5. Neurologie Berlin, Gemeinschaftspraxis, Berlin, Germany. 6. Poliklinika Chocen Neuro, Chocen, Czech Republic; Department of Neurology, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic. 7. Department of Neurology, Vaszary Kolos Hospital, Esztergom, Hungary. 8. Department of Neurology, Jagiellonian University, Krakow, Poland. 9. Parkinson's Disease and Movement Disorders Unit, Department of Neurology, Hospital Clinic, CIBERNED, Barcelona, Spain. 10. Mundipharma Research, Limburg an der Lahn, Germany; Private University Witten/Herdecke, Faculty of Health, Witten, Germany. 11. Mundipharma Research, Limburg an der Lahn, Germany; Rudolf-Buchheim Institute of Pharmacology, Justus-Liebig-Universität Giessen, Germany. 12. Mundipharma Research, Cambridge, UK. 13. Mundipharma Research, Limburg an der Lahn, Germany.
Abstract
BACKGROUND:Pain is a common non-motor symptom of Parkinson's disease. We investigated the analgesic efficacy of prolonged-release oxycodone-naloxone (OXN PR) in patients with Parkinson's disease and chronic, severe pain. METHODS: We did this phase 2 study in 47 secondary care centres in the Czech Republic, Germany, Hungary, Poland, Romania, Spain, and the UK. We enrolled patients with Hoehn and Yahr Stage II-IV Parkinson's disease, at least one type of severe pain, and an average 24-h pain score of at least 6 (assessed on an 11-point rating scale from 0=no pain to 10=pain as bad as you can imagine). Participants were randomly assigned (1:1) with a validated automated system (block size four) to either oral OXN PR or placebo for 16 weeks (starting dose oxycodone 5 mg, naloxone 2·5 mg, twice daily). Patients and investigators were masked to treatment assignment. The primary endpoint was average 24-h pain score at 16 weeks in the full analysis population. This study is registered with EudraCT (2011-002901-31) and ClinicalTrials.gov (NCT01439100). FINDINGS:We enrolled 202 patients; 93 were assigned toOXN PR and 109 to placebo; the full analysis population consisted of 88 patients versus 106 patients. Least squares mean average 24-h pain score at 16 weeks in the full analysis population was 5·0 (95% CI 4·5 to 5·5) in the OXN PR group versus 5·6 (5·1 to 6·0) in the placebo group (difference -0·6, 95% CI -1·3 to 0·0; p=0·058). Similar proportions of patients in each group had adverse events (60/92 [65%] vs 76/109 [70%]), treatment-related adverse events (52/92 [57%] vs 62/109 [57%]), and serious adverse events (5/92 [5%] vs 7/109 [6%]). Treatment-related nausea was more common in the OXN PR group than in the placebo group (16/92 [17%] vs 10/109 [9%]), as was treatment-related constipation (16/92 [17%] vs 6/109 [6%]). INTERPRETATION: The primary endpoint, based on the full analysis population at week 16, was not significant. Nonetheless, the results of this study highlight the potential efficacy of OXN PR for patients with Parkinson's disease-related pain and might warrant further research on OXN PR in this setting. FUNDING: Mundipharma Research.
RCT Entities:
BACKGROUND:Pain is a common non-motor symptom of Parkinson's disease. We investigated the analgesic efficacy of prolonged-release oxycodone-naloxone (OXN PR) in patients with Parkinson's disease and chronic, severe pain. METHODS: We did this phase 2 study in 47 secondary care centres in the Czech Republic, Germany, Hungary, Poland, Romania, Spain, and the UK. We enrolled patients with Hoehn and Yahr Stage II-IV Parkinson's disease, at least one type of severe pain, and an average 24-h pain score of at least 6 (assessed on an 11-point rating scale from 0=no pain to 10=pain as bad as you can imagine). Participants were randomly assigned (1:1) with a validated automated system (block size four) to either oral OXN PR or placebo for 16 weeks (starting dose oxycodone 5 mg, naloxone 2·5 mg, twice daily). Patients and investigators were masked to treatment assignment. The primary endpoint was average 24-h pain score at 16 weeks in the full analysis population. This study is registered with EudraCT (2011-002901-31) and ClinicalTrials.gov (NCT01439100). FINDINGS: We enrolled 202 patients; 93 were assigned to OXN PR and 109 to placebo; the full analysis population consisted of 88 patients versus 106 patients. Least squares mean average 24-h pain score at 16 weeks in the full analysis population was 5·0 (95% CI 4·5 to 5·5) in the OXN PR group versus 5·6 (5·1 to 6·0) in the placebo group (difference -0·6, 95% CI -1·3 to 0·0; p=0·058). Similar proportions of patients in each group had adverse events (60/92 [65%] vs 76/109 [70%]), treatment-related adverse events (52/92 [57%] vs 62/109 [57%]), and serious adverse events (5/92 [5%] vs 7/109 [6%]). Treatment-related nausea was more common in the OXN PR group than in the placebo group (16/92 [17%] vs 10/109 [9%]), as was treatment-related constipation (16/92 [17%] vs 6/109 [6%]). INTERPRETATION: The primary endpoint, based on the full analysis population at week 16, was not significant. Nonetheless, the results of this study highlight the potential efficacy of OXN PR for patients with Parkinson's disease-related pain and might warrant further research on OXN PR in this setting. FUNDING: Mundipharma Research.
Authors: Pablo Martinez-Martin; Anette Schrag; Daniel Weintraub; Alexandra Rizos; Carmen Rodriguez-Blazquez; Kallol Ray Chaudhuri Journal: Mov Disord Clin Pract Date: 2019-02-05
Authors: Santiago Perez-Lloret; Daniel Ciampi de Andrade; Kelly E Lyons; Carmen Rodríguez-Blázquez; Kallol Ray Chaudhuri; Guenther Deuschl; Girgio Cruccu; Cristina Sampaio; Christopher G Goetz; Anette Schrag; Pablo Martinez-Martin; Glenn Stebbins Journal: Mov Disord Clin Pract Date: 2016-06-24