Synergistic Interactions between a KCNQ Channel Opener and Opioids: Open Label Dose finding Phase 2 Trial of Flupirtine in the Treatment of Neuropathic Pain Associated with Cancer
Synergistic Interactions between a KCNQ Channel Opener and Opioids: Open Label Dose finding Phase 2 Trial of Flupirtine in the Treatment of Neuropathic Pain Associated with Cancer
C S Goodchild1, 2, Joanne Nelson 1, 2, Ian Cooke 2, Michael Ashby 3, and Kate Jackson 3
1 Department of Anaesthesia and Perioperative Medicine, Monash University, Clayton Victoria, Australia 3168
2 CNSBio Pty Ltd, 15th Floor, 1 Nicholson St, Melbourne, Victoria, Australia 3000
3 Palliative Care, McCulloch House, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, Australia 3168
Purpose of Study
This study was designed to provide data on the efficacy, dose response, incidence and duration of adverse effects of flupirtine in the treatment of cancer-related neuropathic pain.
Method
This was an eight day, open label, dose escalation study of inpatients in a palliative care unit. After ethics committee approval, patients with moderate to severe neuropathic pain in spite of opioid treatment received an initial dose of flupirtine 100mg four times daily (QID). This dose could be escalated by 100 mg QID every 2 days to a maximum of 300mg QID. Efficacy measures included: 11 point scales measuring average pain and worst pain; a neuropathic pain discriminant score; 11 point scales for quality of life activities and a score of percentage pain relief (0–100%).
Result
Ten Patients were recruited into the study; only one patient was withdrawn because of side effects thought to be due to the flupirtine. There were significant reductions of average pain (p = 0.0008), worst pain (p = 0.0168) and neuropathic pain discriminant scores (p <0.0001; see figure). There were also significant improvements in the quality of life measures (p=0.0017), a reduction of adverse symptoms (p = 0.0017) and an increase in percentage pain relief (p = 0.0078). Additionally there occurred a statistically non-significant downward trend in opioid use. Eight patients elected to continue to take flupirtine after the trial, two taking 200mg QID and the others 100mg QID. Of these eight, six said that flupirtine was of considerable help and two said that it helped only a little.
Conclusion
Flupirtine is effective in the treatment of neuropathic pain caused by cancer when used in combination with opioids. This compound merits further investigation for the treatment of neuropathic pain associated with other aetiologies.
