Clinical evaluation of the first oxycodone once daily prolonged release tablet in moderate to severe chronic pain: a randomized, double-blind, multicenter, cross-over, non-inferiority study to investigate efficacy and safety in comparison with an established oxycodone twice daily prolonged release tablet

Abstract

Objective:

The first oxycodone once daily (OOD) has been developed and after successful pharmacokinetic characterization, therapeutic efficacy and safety were compared to an established oxycodone twice daily (OTD: Oxygesic/OxyContin, Mundipharma).

Design and methods:

A randomized, double-blind, multicenter, cross-over, non-inferiority study was conducted in patients (n = 68) with chronic malignant or non-malignant pain. The new OOD was compared to OTD at identical total daily doses (TDD: 40–120 mg/day) employing intensive, five times daily current pain (0–100 mm visual analog scale, VAS) and twice daily 12 h recalled pain assessments as well as safety parameters such as nausea and sedation (VAS) over 5 days for each treatment (after a 5 day run-in phase).

Results:

There was no significant difference in analgesic potency detected between the two treatments based on 95% CI for difference in the daily mean current pain (−2.09 mm VAS) over 5 days, determined as −5.09 to 0.91 mm VAS. A difference ≤12 mm VAS indicated non-inferiority of OOD, i.e. lack of clinically relevant difference in analgesia. Intake of rescue medication had no effect on study results as evaluated by ANCOVA. The difference in adverse events (AEs) between the two treatments did not reach significance, as 19.1% and 23.5% of patients experienced treatment-related AEs while on OOD and OTD, respectively. Advantages for OOD regarding consistency of analgesia (i.e. use of rescue medication, current and recalled pain) and sedation did not reach statistical significance in this limited study population.

Conclusion:

Despite the small number of patients and short study duration, the results support the conclusion that new OOD is (at least) equivalent to established OTD regarding safety and efficacy.

Keywords::

• Chronic pain
• New once daily prolonged release tablet formulation
• Oxycodone

Transparency

Declaration of funding

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

Declaration of financial/other relationships

M.A.M. has disclosed that she is an employee of the study sponsor, Develco Pharma Schweiz AG. E.A.L. and M.J. have disclosed that they participated in the study as clinical investigators; E.A.L. was also coordinating investigator. They both received investigator fees from Develco Pharma Schweiz AG.

CMRO peer reviewer 1 has no relevant financial or other relationships to disclose. Peer reviewer 2 has disclosed that he is a consultant to Grunenthal and Johnson & Johnson; and that he is on the Speakers’ Bureau of Grunenthal, Mundipharma and Pfizer.

Acknowledgments

The authors thank the investigators from all 12 study sites in Germany and Poland for taking part in this study – Drs. Lux, Hafer, Schütze, Schwittay, Strick in Germany and Drs. Janecki, Cialkowska-Rysz, Chemperek-Wroczek, Korozan, Lembas-Sznabel, Sokalszczuk, Stachowiak in Poland. The sponsor thanks Dr. Gudrun Nold for valuable input to the study design as well as 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 Clinical 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.