Comparative pharmacokinetics of subcutaneous trastuzumab administered via handheld syringe or proprietary single-use injection device in healthy males.
OBJECTIVE
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 (AUC(0-21 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 AUC(0-21 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.
Christchurch Clinical Studies Trust, 31 Tuam Street, Christchurch, New Zealand, chris@ccst.co.nz.
Chris J
CJ
Wynne
Rod B
RB
Ellis-Pegler
Devonie S
DS
Waaka
Christian
C
Schwabe
Michaela
M
Lehle
Dominik
D
Heinzmann
Ranvir
R
Mangat
Chunze
C
Li
Anne E
AE
Dick
Nicola A
NA
Cranshaw
Bert L
BL
Lum
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D004209:Disposable Equipment; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000295:instrumentation; D004342:Drug Hypersensitivity / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D005079:Excipients; D006207:Half-Life; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D008422:Materials Testing; D009520:New Zealand; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012646:Self Administration / Q000295:instrumentation; D013594:Syringes; D000068878:Trastuzumab; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D005079:Excipients; D011994:Recombinant Proteins; D006821:Hyaluronoglucosaminidase; C066852:hyaluronidase PH-20; D000068878:Trastuzumab