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A randomized, placebo-controlled, single ascending-dose study to assess the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous tralokinumab in Japanese healthy volunteers.

Abstract：

:Tralokinumab is a human monoclonal antibody in clinical development for asthma and atopic dermatitis that specifically neutralizes interleukin-13. This phase I, single-blind, randomized, placebo-controlled, single ascending-dose study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of subcutaneous tralokinumab (150, 300, or 600 mg) in thirty healthy Japanese adults. The most frequent treatment-emergent adverse event (TEAE) in all treatment groups was injection-site pain. The frequency and severity of TEAEs was similar across tralokinumab doses. Cmax, AUC(0-t), and AUC(0-inf) increased in a dose-proportional manner, and mean t1/2 ranged from 20 to 25 days. No anti-drug antibodies were detected. A post-hoc pooled population PK modeling analysis, incorporating PK data from this study, demonstrated that Japanese individuals had greater systemic exposure to tralokinumab than non-Japanese individuals. This difference was not clinically relevant and was primarily due to differences in body weight, with lower body weight associated with greater PK exposure. Japanese ethnicity was not a significant predictor of tralokinumab PK. This study indicates that single-dose subcutaneous administration of tralokinumab 150-600 mg was well tolerated in Japanese healthy volunteers, and supports the 300 mg dose selection for Japanese patients with asthma in ongoing clinical trials.

journal_name

Drug Metab Pharmacokinet

journal_title

Drug metabolism and pharmacokinetics

authors

Baverel P,She D,Piper E,Ueda S,Yoshioka T,Faggioni R,Gevorkyan H

doi

10.1016/j.dmpk.2017.12.001

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

150-158

issue

3

eissn

1347-4367

issn

1880-0920

pii

S1347-4367(17)30163-5

journal_volume

33

pub_type

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