Dataset Information

Pharmacokinetic Bioequivalence, Safety, and Immunogenicity of DMB-3111, a Trastuzumab Biosimilar, and Trastuzumab in Healthy Japanese Adult Males: Results of a Randomized Trial.

ABSTRACT: DMB-3111 is a biosimilar trastuzumab drug being jointly developed by Meiji Seika Pharma (Japan) and Dong-A Socio Holdings (Korea). We investigated the bioequivalence of DMB-3111 relative to trastuzumab.The aim of this study was to investigate the bioequivalence between DMB-3111 and trastuzumab and the pharmacokinetic, safety, and immunogenicity of both drugs in healthy Japanese adult males.Seventy healthy Japanese adult males were randomized 1:1 to receive either DMB-3111 or trastuzumab as a single intravenous infusion (6 mg/kg) over 90 min. Bioequivalence was assessed in terms of the pharmacokinetic parameters of both drugs. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Immunogenicity was tested using anti-drug antibody (ADA) assays.The 90% confidence intervals of the treatment differences (DMB-3111 versus trastuzumab) in the mean log-transformed maximum concentration, the area under the concentration-time curves (from 0 min to the last measured value or from 0 min to infinity), mean residence time, and the terminal half-life were within the accepted range for bioequivalence [log(0.80) to log(1.25)]. The frequencies of AEs and adverse drug reactions were similar with both drugs. No ADA reactivity to DMB-3111 or trastuzumab was observed in any subject.DMB-3111, a trastuzumab biosimilar, was bioequivalent to trastuzumab in terms of its pharmacokinetics and showed similar safety after a single intravenous infusion at 6 mg/kg over 90 min in healthy Japanese adult males. DMB-3111 is likely to show similar efficacy and safety profiles to trastuzumab in cancer patients (ClinicalTrials.gov #NCT02100917).

SUBMITTER: Morita J

PROVIDER: S-EPMC4746214 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacokinetic Bioequivalence, Safety, and Immunogenicity of DMB-3111, a Trastuzumab Biosimilar, and Trastuzumab in Healthy Japanese Adult Males: Results of a Randomized Trial.

Morita Jun J Tanaka Masashi M Nomoto Masahiro M Matsuki Shunji S Tsuru Tomomi T Matsuguma Kyoko K Shiramoto Masanari M

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20160201 1

<h4>Background</h4>DMB-3111 is a biosimilar trastuzumab drug being jointly developed by Meiji Seika Pharma (Japan) and Dong-A Socio Holdings (Korea). We investigated the bioequivalence of DMB-3111 relative to trastuzumab.<h4>Objectives</h4>The aim of this study was to investigate the bioequivalence between DMB-3111 and trastuzumab and the pharmacokinetic, safety, and immunogenicity of both drugs in healthy Japanese adult males.<h4>Methods</h4>Seventy healthy Japanese adult males were randomized ...[more]

PMID: 26691837

Similar Datasets

Project description:Background and objectiveA novel tiotropium bromide monodose capsule dry powder inhaler (DPI) formulation and device have been developed. The formulation was based on a spray-dried matrix that enhances the aerosolizaton properties, allowing a less active tiotropium metered dose (13 µg/capsule) while maintaining the same delivered dose (10 µg/actuation). This study describes the pharmacokinetic bioequivalence to the reference product.MethodsThis randomized, two-stage, crossover, semi-replicate (three-way) study was performed in healthy volunteers. In each study period, subjects received a single dose of two capsules (20 μg delivered dose) of the study medication, separated by a 14-day washout period: tiotropium 10 μg delivered dose (Laboratorios Liconsa, Spain) and Spiriva HandiHaler(®) (Boehringer Ingelheim Pharma GmbH & Co KG, Germany). Blood samples were obtained up to 48 h post-dose to evaluate the comparative bioavailability. Tiotropium was measured in plasma by means of dual stage liquid-liquid extraction followed by the two-dimensional ultra-high performance liquid chromatography sensitive sub-pg/mL bioanalytical method. The main pharmacokinetic parameters were maximum plasma concentration (C max), area under the concentration-time curve (AUC) from time zero hours to the last observed concentration at time t (AUC t ), and AUC from time zero hours to 30 min (AUC0.5). Bioequivalence was accepted if the 90.20 % confidence interval (CI) for the ratio test/reference of the primary pharmacokinetic parameters lay within the acceptance range of 80-125 %. Safety assessment was a secondary endpoint.ResultsA total of 30 subjects were randomized and bioequivalence was demonstrated for all primary pharmacokinetic parameters: C max (CI 87.26-106.60 %), AUC t (CI 101.33-111.64 %), and AUC0.5 (CI 97.95-113.49 %). Both study treatments were well tolerated (four non-serious adverse events [AEs] were reported in four subjects: one AE before any product administration, two AEs after test product administration; and one AE after reference product administration).ConclusionsBoth products containing tiotropium 10 µg delivered-dose DPI were bioequivalent and showed good tolerability and a similar safety profile.

Project description:IntroductionThis study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab).MethodsIn this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria.ResultsBaseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies.ConclusionThis study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.Trial registrationANZCTR number: ACTRN12621000573853.

Dataset Information

Pharmacokinetic Bioequivalence, Safety, and Immunogenicity of DMB-3111, a Trastuzumab Biosimilar, and Trastuzumab in Healthy Japanese Adult Males: Results of a Randomized Trial.

Publications

Pharmacokinetic Bioequivalence, Safety, and Immunogenicity of DMB-3111, a Trastuzumab Biosimilar, and Trastuzumab in Healthy Japanese Adult Males: Results of a Randomized Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets