A Phase I Study of the Pharmacokinetics, Safety and Tolerability of a Novel Tocopheryl Phosphate Mixture/Oxymorphone Transdermal Patch System

Abstract

Aim: Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active metabolite (6-OH-oxymorphone). Materials & methods: Fifteen participants received a single application of oxymorphone patches +/− capsaicin for 72 h and were crossed-over for another 72 h. Results: Plasma oxymorphone was detected approximately 7 h and 6-OH-oxymorphone after approximately 18–19 h postapplication of both formulations, respectively. For oxymorphone, median t_max was 24 h, and C_max/C_min ratio was approximately 2.4. The most frequently reported treatment-related adverse event was application site reaction, mainly with capsaicin formulation. Conclusion: Tocopheryl phosphate mixture/oxymorphone transdermal patches can successfully deliver therapeutic amounts of oxymorphone in a sustained manner over 72 h and are well tolerated.

ANZCTR registration number: ACTRN12614000613606

KEYWORDS:

• oxymorphone
• tocopheryl phosphate mixture (TPM)
• transdermal patch

Financial & competing interests disclosure

PD Gavin and AJ Smith are full-time employees of Phosphagenics Limited, Victoria, Australia. LS Simon and T Schlagheck report no conflicts. J Krishnarajah received consulting fees from Linear Clinical Research Ltd, Nedlands, Australia, where the study was conducted. This study was funded by Phosphagenics Limited, Victoria, Australia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was provided by Gemma Williams, Health Writers SLU and S Allawati, Medcommz Ltd (UK). Funding for the writing assistance was provided by Phosphagenics Limited.

Ethical conduct of research

The study was approved by Bellberry Human Research Ethics Committee (Therapeutic Goods Administration [TGA] Clinical Trial Notification number 2014/0405) and performed and conducted in accordance with the standards of International Conference on Harmonization (Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95 – Annotated with TGA Comments) and the Declaration of Helsinki. All subjects were included after having given their informed consent.

Additional information

Funding

PD Gavin and AJ Smith are full-time employees of Phosphagenics Limited, Victoria, Australia. LS Simon and T Schlagheck report no conflicts. J Krishnarajah received consulting fees from Linear Clinical Research Ltd, Nedlands, Australia, where the study was conducted. This study was funded by Phosphagenics Limited, Victoria, Australia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was provided by Gemma Williams, Health Writers SLU and S Allawati, Medcommz Ltd (UK). Funding for the writing assistance was provided by Phosphagenics Limited.