Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): a double-blind, randomised, placebo-controlled trial.
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).


RESULTS
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%]).


CONCLUSIONS
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.


BACKGROUND
Mundipharma Research.
Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurosurgery, University Medical Centre, Goettingen, Germany. Electronic address: ctrenkwalder@gmx.de.
Claudia
C
Trenkwalder
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.
K Ray
KR
Chaudhuri
National Centre of Epidemiology, Carlos III Institute of Health, Madrid, Spain.
Pablo
P
Martinez-Martin
Clinical Investigation Centre 1436, INSERM, Toulouse, France; University Hospital, Toulouse, France.
Olivier
O
Rascol
Neurologie Berlin, Gemeinschaftspraxis, Berlin, Germany.
Reinhard
R
Ehret
Poliklinika Chocen Neuro, Chocen, Czech Republic; Department of Neurology, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic.
Martin
M
Vališ
Department of Neurology, Vaszary Kolos Hospital, Esztergom, Hungary.
Maria
M
Sátori
Department of Neurology, Jagiellonian University, Krakow, Poland.
Anna
A
Krygowska-Wajs
Parkinson's Disease and Movement Disorders Unit, Department of Neurology, Hospital Clinic, CIBERNED, Barcelona, Spain.
Maria J
MJ
Marti
Mundipharma Research, Limburg an der Lahn, Germany; Private University Witten/Herdecke, Faculty of Health, Witten, Germany.
Karen
K
Reimer
Mundipharma Research, Limburg an der Lahn, Germany; Rudolf-Buchheim Institute of Pharmacology, Justus-Liebig-Universität Giessen, Germany.
Alexander
A
Oksche
Mundipharma Research, Cambridge, UK.
Mark
M
Lomax
Mundipharma Research, Cambridge, UK.
Julia
J
DeCesare
Mundipharma Research, Limburg an der Lahn, Germany.
Michael
M
Hopp
D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D010098:Oxycodone / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000150:complications / Q000188:drug therapy*; D010300:Parkinson Disease / Q000150:complications*; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009270:Naloxone; D010098:Oxycodone