Abstract
Purpose
To demonstrate pharmacokinetic (PK) comparability for a single dose of 600 mg subcutaneous (SC) trastuzumab, administered via a novel single-use injection device (SID) or handheld syringe in 119 randomized healthy male subjects.
Methods
The co-primary PK endpoints area under the time–concentration curve from the start of dosing to day 22 (AUC0–21 days) and maximum observed trastuzumab serum concentration (C max) were dose-normalized and body-weight-adjusted, and compared using geometric mean ratios (GMRs). SID performance, injection site pain, adverse events, and antidrug antibodies (ADAs) were assessed.
Results
GMRs and 90 % confidence intervals (CIs) were 1.01 (0.96–1.07) for AUC0–21 days and 1.02 (0.96–1.10) for C max, which fell within the prespecified bioequivalence range (0.80–1.25). No SID quality issues or failures occurred. Adverse events were mostly mild, with no deaths, adverse event-related withdrawals, or life-threatening, cardiac, or serious events reported. The ADA rate was low, and no neutralizing antibodies were detected.
Conclusions
Trastuzumab SC via SID demonstrated comparable PK and safety to handheld syringe administration. SID performance was very satisfactory.
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Acknowledgments
This study was funded by F. Hoffmann-La Roche. We would like to acknowledge all investigators participating in this trial in addition to the Global Study Management team members and Luis Herráez-Baranda. We would also like to thank Marcel Both for his involvement in SID development and for providing onsite training in use of the SID. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche.
Conflict of interest
M.L. and D.H. are employees of F. Hoffmann-La Roche Ltd. R.M., C.L., and B.L.L. are employees of Genentech Inc. The remaining authors had no potential conflict of interest to disclose.
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280_2013_2273_MOESM2_ESM.tif
Supplementary Fig 1 Patient disposition. AUC0–21 days, area under the time–concentration curve from start of dosing to day 22; Cday 21, concentration at day 22; Cmax, maximum serum concentration; PK, pharmacokinetics; SC, subcutaneous; SD, standard deviation; SID, single-use injection device; Tmax, time to maximum serum concentration. a Exclusion criteria met (n = 37), inclusion criteria not met (n = 22), withdrawn consent (n = 10), other (n = 1). b Ineligibility (n = 3), withdrawn consent (n = 1) (TIFF 131 kb)
280_2013_2273_MOESM3_ESM.tif
Supplementary Fig 2 Mean injection site pain assessments on 100-mm VAS. Higher scores correspond to greater pain intensity. SD, standard deviation; SID, single-use injection device; VAS, visual analog scale (TIFF 137 kb)
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Wynne, C.J., Ellis-Pegler, R.B., Waaka, D.S. et al. Comparative pharmacokinetics of subcutaneous trastuzumab administered via handheld syringe or proprietary single-use injection device in healthy males. Cancer Chemother Pharmacol 72, 1079–1087 (2013). https://doi.org/10.1007/s00280-013-2273-z
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DOI: https://doi.org/10.1007/s00280-013-2273-z