Comparative pharmacokinetics of an adalimumab biosimilar SB5 administered via autoinjector or prefilled syringe in healthy subjects

Donghoon Shin, Younju Lee, Deokyoon Jeong, Rod Ellis-Pegler, Donghoon Shin, Younju Lee, Deokyoon Jeong, Rod Ellis-Pegler

Abstract

Purpose: The objective of this study was to demonstrate comparable pharmacokinetic (PK), safety, and tolerability parameters of the adalimumab biosimilar SB5 administered via autoinjector (AI) pen or prefilled syringe (PFS).

Patients and methods: In this phase 1, randomized, open-label, single-dose, parallel-group study, healthy subjects aged 18-55 years were randomized 1:1 to a single dose of 40 mg SB5 delivered subcutaneously via AI or PFS. PK parameters, safety, and tolerability were assessed for 57 days post-dose. The primary endpoint was area under the curve (AUC) of the concentration-time curve from zero to infinity (AUCinf) and from zero to last quantifiable concentration (AUClast) and maximum serum concentration (Cmax). Equivalence was determined using predefined margins of 0.80-1.25 for the 90% CI for the ratio of SB5 AI to SB5 PFS.

Results: Ninety-five subjects were randomized to each group. Mean serum concentration-time profiles were superimposable between groups. Mean values for AUCinf, AUClast, and Cmax were similar between the SB5 AI and SB5 PFS groups. For the primary endpoints, the 90% CIs for the ratio of geometric least squares means for SB5 AI to SB5 PFS ranged between 0.9503 and 1.2240, which were all within the equivalence margin of 0.80-1.25. Incidence of treatment-emergent adverse events and injection site reactions was similar between groups.

Conclusion: In healthy subjects receiving a single dose of SB5 via AI or PFS, PK parameters and corresponding 90% CIs were within the predefined margins, showing bioequivalence between the two delivery methods. Safety and tolerability assessments were also similar between groups.

Clinicaltrialsgov identifier: NCT02326233.

Eudract number: 2014-005178-12.

Keywords: TNF-alpha inhibitor; bioequivalence; clinical trial; rheumatoid arthritis; safety.

Conflict of interest statement

Disclosure D Shin, Y Lee, and D Jeong are employees of Samsung Bioepis Co., Ltd. D Shin reports personal fees from Samsung Bioepis during the conduct of the study. Y Lee reports owning Samsung Bioepis Co., Ltd. stock outside the submitted work. R Ellis-Pegler is a principal investigator and physician consultant for Auckland Clinical Studies (ACS), Auckland, New Zealand. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Subject disposition summary. Notes:aOne subject in the SB5 AI group was non-compliant with the medication dosage because the AI device malfunctioned and the full dose of study drug was not administered. The subject was not included in the PK population but was included in the safety population. Abbreviations: AI, autoinjector; PFS, prefilled syringe; PK, pharmacokinetic.
Figure 2
Figure 2
Mean serum concentration profiles (pharmacokinetic population). Notes: Top image: Linear scale. Bottom image: Semilogarithmic scale. Abbreviations: AI, autoinjector; PFS, prefilled syringe.

References

    1. Humira® (adalimumab) Summary of product characteristics. Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG; 2018.
    1. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960–977.
    1. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016;68(1):1–25.
    1. Dörner T, Strand V, Castañeda-Hernández G, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis. 2013;72(3):322–328.
    1. Hirsch BR, Lyman GH. Biosimilars: a cure to the U.S. health care cost conundrum? Blood Rev. 2014;28(6):263–268.
    1. European Medicines Agency . Imraldi: Summary of Opinion (initial authorisation) EMA; 2017. [Accessed September 10, 2018]. Available from: .
    1. Shin D, Lee Y, Kim H, Körnicke T, Fuhr R. A randomized phase I comparative pharmacokinetic study comparing SB5 with reference adalimumab in healthy volunteers. J Clin Pharm Ther. 2017;42(6):672–678.
    1. Weinblatt ME, Baranauskaite A, Niebrzydowski J, et al. Phase III randomized study of SB5, an adalimumab biosimilar, versus reference adalimumab in patients with moderate-to-severe rheumatoid arthritis. Arthritis Rheumatol. 2018;70(1):40–48.
    1. Borrás-Blasco J, Gracia-Pérez A, Rosique-Robles JD, Casterá MD, Abad FJ. Acceptability of switching adalimumab from a prefilled syringe to an autoinjection pen. Expert Opin Biol Ther. 2010;10(3):301–307.
    1. Kivitz A, Cohen S, Dowd JE, et al. Clinical assessment of pain, tolerability, and preference of an autoinjection pen versus a prefilled syringe for patient self-administration of the fully human, monoclonal antibody adalimumab: the TOUCH trial. Clin Ther. 2006;28(10):1619–1629.
    1. US Food and Drug Administration Guidance for Industry Rheumatoid Arthritis: Developing Drug Products for Treatment. 2013
    1. Phillips JT, Fox E, Grainger W, Tuccillo D, Liu S, Deykin A. An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects. BMC Neurol. 2011;11:126.
    1. Kivitz A, Baret-Cormel L, van Hoogstraten H, et al. Usability and Patient Preference Phase 3 Study of the Sarilumab Pen in Patients with Active Moderate-to-Severe Rheumatoid Arthritis. Rheumatol Ther. 2018;5(1):231–242.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren