Efficacy of a new once daily hydromorphone formulation in comparison with twice daily administration in chronic pain: a randomized, double-blind, cross-over study

Objective Efficacy and safety of a novel multiple-unit hydromorphone once daily (HOD) was compared to an established hydromorphone twice daily (HTD) regimen in patients with moderate-to-severe chronic pain. Design and methods The results from a randomized, double-blind, multicenter, cross-over trial in patients (n=37) with chronic malignant or non-malignant pain are reported. The primary efficacy parameter was current pain on 0-100mm VAS assessed four times daily and prior to intake of rescue medication (immediate-release hydromorphone) throughout the last 5 days with each treatment (after an 8day build-up period to avoid carry-over effects). Total daily dose of hydromorphone (TDD: 8-32mg/day) was kept stable during the double-blind treatment phase. Results The difference observed in mean current pain (-0.92mm VAS) over the 5day assessment period between HOD and HTD (28.44mm vs. 29.36mm VAS) was found to lack clinical relevance, as the 95% CI (-4.10 to 2.28mm VAS) did not exceed the prespecified limit for non-inferiority of 9mm VAS. Results from the full analysis set were consistent with per protocol data confirming robustness, as did the data for 12h recalled pain assessed at 08:00h and 20:00h, showing no significant differences between once and twice daily medication. Both treatments produced effective and stable pain control with only minor day-to-day and intra-day fluctuations. Switching between treatments was suitable, considering both efficacy and safety, as no relevant or significant differences in adverse events were seen (25.0% HOD, 24.3% HTD). Most frequently typical side-effects of opioid therapy were observed, such as nausea, vomiting and headache. Conclusion Although this study was of short duration and included a limited number of patients, the results confirm that the new HOD is as effective and safe as the established HTD.