Prolonged-release oxycodone / naloxone shows significant efficacy for the reduction of musculoskeletal pain and nocturnal pain for patients with severe pain from Parkinson’s disease compared with placebo, according to results of a double-blind study presented at the First Congress of the European Academy of Neurology (EAN).
Prolonged-release oxycodone / naloxone also demonstrated no unanticipated adverse events.
“Pain is a severe and common non-motor symptom of Parkinson’s disease, and affects approximately two-thirds of patients,” explained Anna Sauerbier, MD, National Parkinson Foundation, Parkinson’s Centre of Excellence, King’s College Hospital, London, United Kingdom, speaking here on June 20. There remains a lack of clinical guidance for pain management in this setting, she added.
Although opioid analgesics are widely used for moderate-to-severe pain, there remains little evidence of the safety and efficacy of their use for patients with Parkinson’s disease. Further, the combination of the opioid analgesic oxycodone with the opioid receptor antagonist naloxone is known to provide comparable analgesic efficacy to oxycodone alone, while reducing opioid-induced constipation.
Dr. Sauerbier and colleagues randomised patients with chronic, severe Parkinson’s disease-related pain to placebo (n = 106, mean age, 65.7 years; male, 53.8%) or active treatment (n = 88, mean age, 66.7 years; male, 48.9%) with prolonged-release oxycodone / naloxone (5/2.5 mg twice daily; titrated to maximum 20/10 mg twice daily) for 16 weeks. This was followed by an open-label phase with active treatment for 4 weeks, and 7 to 10 days safety follow-up.
The subjects (≥25 years old) were required to have severe pain for 1 or more subsections of the King’s Parkinson’s disease pain scale, and a mean 24-hour pain score of 6 or more on an 11-point scale (0 to 10) over 7 days prior to randomisation. All subjects continued their PD treatments throughout the study.
With similar baseline clinical characteristics across the groups, the subjects had a mean duration of Parkinson’s disease-related pain of 3.4 years, and a mean 24-hour pain score of 7.3. The pain was mainly musculoskeletal.
The primary endpoint of mean 24-hour pain scores over the 7 days preceding week 16 of treatment was numerically reduced, but did not reach statistical significance when active treatment was compared with placebo (least squares mean difference, -0.6; P = .058).
For secondary endpoints, the benefits as least-squares mean difference for active treatment showed significance at 4 weeks (-0.6; P = .018), 8 weeks (-0.7; P = .011), and 12 weeks (-0.7; P = .021). Dr. Sauerbier noted that, according to the per-protocol analysis, the benefit of active treatment reached significance for week 16 (-0.9; P = .010).
Also, responder rates for mean 24-hour pain at week 16 for prolonged-release oxycodone / naloxone were significantly greater compared with placebo, (47.7% vs 34.0%; P = .021).
There were again significant benefits as least-squares mean difference for active treatment when analysed specifically in terms of severe musculoskeletal pain (-0.9; P = .023) and nocturnal pain (-1.62; P = .010).
In the safety analysis, constipation was not reported as a serious adverse event, and rarely resulted in study discontinuation. Similarly, there were no negative effects for active treatment on gastrointestinal function, and few patients suffered from distressing dreams or hallucinations at night.
“Further studies of [prolonged-release oxycodone / naloxone] for the treatment of severe Parkinson’s disease-related pain are warranted,” the authors concluded.