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

Abstract

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 0–100 mm 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 8 day build-up period to avoid carry-over effects). Total daily dose of hydromorphone (TDD: 8–32 mg/day) was kept stable during the double-blind treatment phase.

Results The difference observed in mean current pain (−0.92 mm VAS) over the 5 day assessment period between HOD and HTD (28.44 mm vs. 29.36 mm VAS) was found to lack clinical relevance, as the 95% CI (−4.10 to 2.28 mm VAS) did not exceed the prespecified limit for non-inferiority of 9 mm VAS. Results from the full analysis set were consistent with per protocol data confirming robustness, as did the data for 12 h recalled pain assessed at 08:00 h and 20:00 h, 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.

Keywords:

• Chronic pain
• Hydromorphone
• New once daily prolonged-release tablet formulation
• Non-inferiority

Declaration of funding

The study was funded by study sponsor Develco Pharma Schweiz AG.

Declaration of financial/other relationships

M.A.M. and H.R. have disclosed that they are employees of the study sponsor Develco Pharma Schweiz AG. A.S. and C.S. have disclosed that they participated in the study as clinical investigator and study coordinator, receiving investigator fees from Develco Pharma Schweiz AG. G.E.N. has disclosed that she provided valuable input to the study design and data interpretation acting as a consultant to Develco Pharma Schweiz AG.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank the investigators from all eight study sites in Germany and Poland for taking part in this study – Drs. Miles, Schwittay, Wolf, and Schenk in Germany and Drs. Chemperek-Wroczek, Cialkowska-Rysz, Korozan, and Lembas-Sznabel in Poland. The sponsor thanks Dr. Andreas Völp, Prof. Dr. Gerd Geisslinger and Per Settergren Sørensen for their contributions as members of the independent data monitoring committee. Harrison Clinical Research GmbH (now SynteractHCR Deutschland GmbH), Munich, Germany provided services as Contract Research Organisation (CRO) including data management and statistical evaluation. The authors also thank Dr. Stephan Döppenschmitt for providing editorial support, which was also funded by Develco Pharma Schweiz AG.

Notes

* Palladon Retard is a registered trade name of Mundipharma, Germany

* Palladone is a registered trade name of Mundipharma, Germany