Dataset Information

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

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.

SUBMITTER: Shin D

PROVIDER: S-EPMC6225915 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Shin Donghoon D Lee Younju Y Jeong Deokyoon D Ellis-Pegler Rod R

Drug design, development and therapy 20181105

<h4>Purpose</h4>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).<h4>Patients and methods</h4>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 ...[more]

PMID: 30464411

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Project description:IntroductionThe aim of the study was to demonstrate the bioequivalence, and compare the safety and tolerability of MSB11022, a proposed biosimilar of adalimumab, when delivered by either an autoinjector (AI) or a pre-filled syringe (PFS).MethodsIn this pharmacokinetic (PK), parallel group, open-label study, 216 healthy volunteers were randomised 1:1 to receive a single subcutaneous injection of a 40 mg/0.8 mL dose of MSB11022 administered via AI or PFS. Coprimary PK endpoints were maximum observed concentration (Cmax), area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t), and AUC from time 0 extrapolated to infinity (AUC0-inf). PK equivalence between the AI and PFS administration methods was declared if the 90% confidence intervals (CIs) for the ratio of geometric least square means was entirely contained within the 80-125% equivalence margin for all coprimary endpoints. Safety and tolerability were also evaluated.ResultsThe 90% CI for the three coprimary PK endpoints (Cmax, AUC0-t and AUC0-inf) were entirely contained within the predefined equivalence margins of 80-125%. Mean serum concentration-time profiles were similar following injection via AI or PFS. Treatment-emergent adverse events (TEAEs) were comparable across both treatment groups. Study device-related TEAEs were reported by 11.3% and 13.1% of subjects in the AI and PFS treatment groups, respectively. Study drug-related TEAEs were reported by 28.3% and 34.6% of subjects in the AI and PFS treatment groups, respectively. Few subjects experienced injection-site reactions, mainly pain and erythema, regardless of the administration method.ConclusionDelivery of MSB11022 via an AI is bioequivalent to delivery via a PFS. The safety and tolerability profile of MSB11022 was comparable across administration methods. The development of an AI for MSB11022 provides a choice of self-injection devices available to patients, potentially improving treatment compliance.Trial registrationClinicalTrials.gov trial identifier: NCT04018599.

Project description:IntroductionSB5 is an approved biosimilar of adalimumab, a monoclonal anti-tumor necrosis factor (anti-TNF) antibody. This study compared pharmacokinetics (PK), safety, tolerability, and immunogenicity between a new high-concentration, low-volume, and citrate-free formulation (40 mg/0.4 ml, SB5-HC) and the current low-concentration formulation with higher volume (40 mg/0.8 ml, SB5-LC) to evaluate the bioequivalence of the two formulations.MethodsThis study was a randomized, single-blind, two-arm, parallel-group, single-dose study in healthy male subjects. Subjects were randomized to receive either SB5-HC or SB5-LC via subcutaneous injection using a pre-filled syringe. Primary endpoints were the area under the curve of the concentration-time curve from zero to infinity (AUCinf) and maximum serum concentration (Cmax). Bioequivalence was achieved if the 90% confidence intervals (CIs) for the ratios of the geometric least squares mean (LSMean) of primary endpoints were within the pre-defined bioequivalence margins of 0.80-1.25. Secondary endpoints included safety, tolerability, and immunogenicity.ResultsSubjects (n = 188) were randomized to SB5-HC (n = 94) or SB5-LC (n = 94). Baseline characteristics were comparable between the two treatment groups. The mean values for AUCinf and Cmax were similar between the SB5-HC and SB5-LC groups. For the primary endpoints, the geometric LSMean ratios (90% CI) for AUCinf and Cmax were 0.920 (0.8262-1.0239) and 0.984 (0.9126-1.0604), respectively, placing the corresponding 90% CIs well within the pre-defined bioequivalence margin of 0.80-1.25. All treatment-emergent adverse events (TEAEs) were considered mild to moderate and were reported for 44.7% and 51.1% of subjects in the SB5-HC and SB5-LC groups, respectively. Immunogenicity assessed by frequency of occurrence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) was comparable between groups.ConclusionsThis bridging study demonstrated PK equivalence and comparable safety and tolerability of subcutaneous injection of SB5 via SB5-HC or SB5-LC.ClinicaltrialsGOV IDENTIFIER: https://clinicaltrials.gov/ct2/show/NCT04514796 .

Project description:AIMS:The aim of the study was to compare the pharmacokinetics (PK), safety and tolerability of the proposed adalimumab biosimilar MSB11022 (Merck) with Humira(®) (AbbVie), sourced from both the US (US reference product [US-RP]) and Europe (European reference medicinal product [EU-RMP]). METHODS:In this phase 1 double-blind, parallel group trial (EMR200588-001), 213 healthy volunteers were randomized 1 : 1 : 1 to receive a single dose (40 mg) of MSB11022, US-RP or EU-RMP in order to achieve 80% power assuming a 5% difference among groups and a 10% dropout rate. Following a preplanned blinded sample size re-assessment after more than 50% of the originally planned subjects had been observed, the sample size was increased to 237 (79 per arm) to ensure 213 completers. Primary PK endpoints analyzed by non-compartmental methods, were area under the curve (AUC) from time 0 extrapolated to infinity (AUC(0,?)), maximum observed concentration (Cmax ), and AUC from time 0 to the last quantifiable concentration (AUC(0,tlast )). PK equivalence was declared if the 90% CI for the test : reference ratio lay within the 80-125% equivalence margin. Bioequivalence was demonstrated if all three PK parameters met the PK equivalence criteria. Safety and tolerability were also evaluated. RESULTS:Mean serum concentration-time profiles for the three treatments were similar. MSB11022 demonstrated PK equivalence to US-RP and EU-RMP for all primary endpoints. The geometric means of AUC(0,?), Cmax and AUC(0,tlast ) following a single dose of MSB11022 were 2276.05 ?g ml(-1) h, 3.44 ?g ml(-1) and 1983.90 ?g ml(-1) h, respectively. Adverse events (AEs) were similar across all groups, with treatment-emergent AEs (TEAEs) reported by 62.8%, 56.3% and 62.0% of subjects within the MSB11022, US-RP and EU-RMP groups, respectively. Most of the TEAEs were considered mild and unrelated to study drug. No deaths or severe AEs related to the study drug were reported. CONCLUSIONS:Bioequivalence between MSB11022, US-RP and EU-RMP was demonstrated. Safety, tolerability and immunogenicity profiles were similar between subjects receiving MSB11022 and US-RP or EU-RMP. These data support the further clinical evaluation of MSB11022 as a proposed biosimilar of adalimumab.

Dataset Information

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

Publications

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

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