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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 10/2023

Open Access 23-08-2023 | Pharmacokinetics | Original Research Article

Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies

Authors: Laiyi Chua, Stuart Friedrich, Xin Cindy Zhang

Published in: Clinical Pharmacokinetics | Issue 10/2023

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Abstract

Background and Objective

Mirikizumab is a humanized anti-interleukin-23-p19 monoclonal antibody being developed for ulcerative colitis and Crohn’s disease. This analysis characterized mirikizumab pharmacokinetics using phase II and III trial data from patients with moderately to severely active ulcerative colitis.

Methods

Serum pharmacokinetic data in patients receiving mirikizumab 50–1000 mg intravenously every 4 weeks as induction treatment and mirikizumab 200 mg subcutaneously every 4 or 12 weeks as maintenance treatment across three trials (N = 1362) were analyzed using non-linear mixed-effects modeling. Covariate effects on mirikizumab exposure were evaluated using simulation-based estimations.

Results

Mirikizumab pharmacokinetics was best described by a linear two-compartment model with first-order absorption. Clearance, volume of distribution for central and peripheral compartments, and half-life were estimated at approximately 0.022 L/h (linear), 3.11 L and 1.69 L, and 9.5 days, respectively. Statistically significant effects of body weight and serum albumin levels on clearance, body weight on central and peripheral volumes of distribution, and body mass index on bioavailability were observed but effects were small relative to random inter-individual variability (% coefficient of variation: 18–64%). The subcutaneous bioavailability of mirikizumab was 48%.

Conclusions

Mirikizumab displayed pharmacokinetic characteristics typical of a monoclonal antibody where clearance increased with body weight and decreased with the albumin level, and bioavailability decreased with body mass index. These effects were small relative to random variability, indicating that a dose adjustment for patient factors is not required.

Clinical Trial Registration

ClinicalTrials.gov: NCT02589665 (28 October, 2015), NCT03518086 (8 May, 2018), NCT03524092 (14 May, 2018).
Appendix
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Metadata
Title
Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies
Authors
Laiyi Chua
Stuart Friedrich
Xin Cindy Zhang
Publication date
23-08-2023
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 10/2023
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-023-01281-z

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