Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA)

A double-blind, randomised, placebo-controlled trial

PANDA study group

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1161-1170
Number of pages10
JournalThe Lancet Neurology
Volume14
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

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Oxycodone
Naloxone
Parkinson Disease
Randomized Controlled Trials
Placebos
Pain
Therapeutics
Population
Secondary Care Centers
Romania
Hungary
Czech Republic
Poland
Constipation
Least-Squares Analysis
Research
Chronic Pain
Spain
Nausea
Germany

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{3a75ca1f445f4af79cf180fea9186ae0,
title = "Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): A double-blind, randomised, placebo-controlled trial",
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 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.",
author = "{PANDA study group} and Claudia Trenkwalder and Chaudhuri, {K. Ray} and Pablo Martinez-Martin and Olivier Rascol and Reinhard Ehret and Martin Vališ and Maria S{\'a}tori and Anna Krygowska-Wajs and Marti, {Maria J.} and Karen Reimer and Alexander Oksche and Mark Lomax and Julia DeCesare and Michael Hopp and M. Bal{\'a}ž and R. Jech and P. Kanovsk{\'y} and L. Pazdera and V. Mach and D. Roubcov{\'a} and M. Kuchar and J. Classen and D. Dressler and S. Muhlack and U. Polzer and J. Schwarz and M. Sommer and J. Kassubek and A. K{\"u}hn and K. Eggert and C. Winkler and A. Ceballos-Baumann and H. Reichman and A. Cs{\'a}nyi and A. Folyovich and N. L{\'e}vai and J. Lajtos and M. Zsolnai and L. V{\'e}csei and P. P{\'o}lrola and A. Szczepanska-Szerej and A. Honczarenko and A. Kaminska and A. Potemkowski and G. Opala and A. Klimek and M. Rudzinska and V. Albu and C. Enache and C. Falup-Pecurariu",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/S1474-4422(15)00243-4",
language = "English",
volume = "14",
pages = "1161--1170",
journal = "The Lancet Neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "12",

}

TY - JOUR

T1 - Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA)

T2 - A double-blind, randomised, placebo-controlled trial

AU - PANDA study group

AU - Trenkwalder, Claudia

AU - Chaudhuri, K. Ray

AU - Martinez-Martin, Pablo

AU - Rascol, Olivier

AU - Ehret, Reinhard

AU - Vališ, Martin

AU - Sátori, Maria

AU - Krygowska-Wajs, Anna

AU - Marti, Maria J.

AU - Reimer, Karen

AU - Oksche, Alexander

AU - Lomax, Mark

AU - DeCesare, Julia

AU - Hopp, Michael

AU - Baláž, M.

AU - Jech, R.

AU - Kanovský, P.

AU - Pazdera, L.

AU - Mach, V.

AU - Roubcová, D.

AU - Kuchar, M.

AU - Classen, J.

AU - Dressler, D.

AU - Muhlack, S.

AU - Polzer, U.

AU - Schwarz, J.

AU - Sommer, M.

AU - Kassubek, J.

AU - Kühn, A.

AU - Eggert, K.

AU - Winkler, C.

AU - Ceballos-Baumann, A.

AU - Reichman, H.

AU - Csányi, A.

AU - Folyovich, A.

AU - Lévai, N.

AU - Lajtos, J.

AU - Zsolnai, M.

AU - Vécsei, L.

AU - Pólrola, P.

AU - Szczepanska-Szerej, A.

AU - Honczarenko, A.

AU - Kaminska, A.

AU - Potemkowski, A.

AU - Opala, G.

AU - Klimek, A.

AU - Rudzinska, M.

AU - Albu, V.

AU - Enache, C.

AU - Falup-Pecurariu, C.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

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