characteristics with those of the reference product. As these studies are specifically designed to assess pharmacokinetic endpoints these studies are typically conducted in healthy volunteers but may be conducted in participants depending upon a range of factors such as the potential risks associated with the use of the agent. During the current update period, four phase I pharmacokinetic studies comparing a potential biosimilar medicine with a reference product were reported. In each of the trials reported, the potential biosimilar met the pre-specified acceptance criteria for the relevant pharmacokinetic/pharmacodynamic parameter endpoints. A summary of the results of these studies are presented in the table below (Table 1). Table 1: Summary of phase I pharmacokinetic studies of potential biosimilar medicines Biosimilar Reference PK Outcomes (and PD Immunogenicity Design Population Reference Candidate Product where reported) Outcomes Adalimumab M923 Humira Randomised, Healthy 90%CI for the ratio At day 71 the [1] (Momenta) (US and double-blind, participants between the proportion of EU) three-arm, (n=324, geometric means of confirmed ADA dose study randomised 1:1:1) the responses from time zero increased in all extrapolated to study groups to infinite time (AUCinf), M923 = 78.0%, AUC from time 0 to US Humira = 336hrs concentration 73.1%, and EU (AUC336) and Humira = 75.7% maximal plasma The presence of concentration (Cmax) IgE was were within the confirmed in 13 predefined subjects (2 in the bioequivalence M923 arm, 8 in interval of 0.80–1.25 the US Humira arm, and 3 in the EU Humira arm) Biosimilar Reference PK Outcomes (and PD Immunogenicity Study Design Study Population Reference Candidate Product where reported) Outcomes Insulin lispro
characteristics with those of the reference product. As these studies are specifically designed to assess pharmacokinetic endpoints these studies are typically conducted in healthy volunteers but may be conducted in participants depending upon a range of factors such as the potential risks associated with the use of the agent. During the current update period, four phase I pharmacokinetic studies comparing a potential biosimilar medicine with a reference product were reported. In each of the trials reported, the potential biosimilar met the pre-specified acceptance criteria for the relevant pharmacokinetic/pharmacodynamic parameter endpoints. A summary of the results of these studies are presented in the table below (Table 1). Table 1: Summary of phase I pharmacokinetic studies of potential biosimilar medicines Biosimilar Candidate Reference Product Design Population PK Outcomes (and PD where reported) Immunogenicity Outcomes Reference Adalimumab M923 (Momenta) Humira (US and EU) Randomised, double-blind, three-arm, study Healthy participants (n=324, randomised 1:1:1) 90%CI for the ratio between the geometric means of the from time zero extrapolated to infinite time (AUCinf), AUC from time 0 to 336hrs concentration (AUC336) and maximal plasma concentration (Cmax) were within the predefined bioequivalence interval of 0.80–1.25 At day 71 the proportion of confirmed ADA responses increased in all study groups to M923 = 78.0%, US Humira = 73.1%, and EU Humira = 75.7% The presence of IgE was confirmed in 13 subjects (2 in the M923 arm, 8 in the US Humira arm, and 3 in the EU Humira arm) [1] Biosimilar Candidate Reference Product Study Design Study Population PK Outcomes (and PD where reported) Immunogenicity Outcomes Reference Insulin lispro dose
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