An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males

Abstract

Aim: To assess the bioavailability and pharmacokinetics of CAT-354, an anti-IL-13 human monoclonal IgG4 antibody, following subcutaneous (s.c.) and intravenous (i.v.) administration.

Methods: This was a single-dose, randomized, open-label, parallel-group bioavailability study. Healthy male subjects aged 20-54 years were randomly assigned to one of three dose groups (n= 10/group) to receive CAT-354: 150 mg i.v.; 150 mg s.c. or 300 mg s.c. (two 150 mg injections). Serum pharmacokinetics, adverse events (AEs), vital signs, electrocardiograms and laboratory parameters were assessed.

Results: CAT-354 showed bioavailability of 62% and 60% after 150 mg and 300 mg s.c. doses, respectively, and linear pharmacokinetics over the dose range tested. Peak serum concentrations in the s.c. groups occurred after 3-9 (median 5) days, with a mean elimination half-life of 19.2 +/- 3.1 days (150 mg) and 19.4 +/- 3.59 days (300 mg) after s.c. and 21.4 +/- 2.46 days after i.v. administration. Volume of distribution at steady state (V(ss)) was 4960 +/- 1440 ml kg(-1) after i.v. (slightly greater than plasma volume). Average apparent clearances (CL/F) were 292 +/- 82.3 and 307 +/- 109 ml day(-1) after 150 and 300 mg s.c., respectively; systemic CL of 188 +/- 84.0 ml day(-1) after i.v. dosing was consistent with endogenous IgG and reticuloendothelial elimination. No severe or serious AEs occurred. Among 40 reported AEs, 25 were headache, sinus disorders/respiratory symptoms and changes in body temperature perception.

Conclusions: CAT-354 exhibited bioavailability of approximately 60% when given s.c. to healthy male subjects.

Figures

Figure 1

Flowchart of subject assignment and treatment through the study

Figure 2

Serum concentration vs. time profile of single doses of CAT-354 at doses of 150 mg s.c. (), 300 mg s.c. (), and 150 mg i.v. () administered by s.c. injection or i.v., infusion

Figure 3

(A) Observed and model-predicted profiles of CAT-354 following 150 mg s.c. administration. Solid line: mean prediction. Dashed lines: 5th and 95th quantiles. Shaded area: 90% prediction interval. (B) Observed and model-predicted profiles of CAT-354 following 300 mg s.c. administration. Solid line: mean prediction. Dashed lines: 5th and 95th quantiles. Shaded area: 90% prediction interval. (C) Observed and model-predicted profiles of CAT-354 following 150 mg i.v. administration. Solid line: mean prediction. Dashed lines: 5th and 95th quantiles. Shaded area: 90% prediction interval