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Clinical Pharmacokinetics

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Open Access 01-03-2019 | Original Research Article

Population Pharmacokinetics of the Interleukin-23 Inhibitor Risankizumab in Subjects with Psoriasis and Crohn’s Disease: Analyses of Phase I and II Trials

Authors: Ahmed A. Suleiman, Amit Khatri, Mukul Minocha, Ahmed A. Othman

Published in: Clinical Pharmacokinetics | Issue 3/2019

Abstract

Background and Objectives

Risankizumab is a humanized anti-interleukin-23 monoclonal antibody in development for the treatment of several inflammatory diseases. This work characterized the pharmacokinetics of risankizumab and evaluated covariates that may affect its exposures using phase I and II trial data in subjects with psoriasis and Crohn’s disease.

Methods

Plasma concentration measurements from a phase I study and a phase II study in subjects with psoriasis (n = 157; single doses of 0.01–5 mg/kg intravenously, 0.25–1 mg/kg subcutaneously, and 18 mg subcutaneously, and multiple doses of 90 and 180 mg subcutaneously), and a phase II study in subjects with Crohn’s disease (n = 115; doses of 200 or 600 mg intravenously every 4 weeks followed by 180 mg subcutaneously every 8 weeks) were analyzed using non-linear mixed-effects modeling. The model was qualified using bootstrap and simulation-based diagnostics.

Results

A two-compartment model with first-order absorption and elimination described the pharmacokinetics of risankizumab. Considering the body weight and baseline albumin central tendency differences between disease populations, risankizumab clearance, steady-state volume of distribution, and terminal-phase elimination half-life were estimated to be approximately 0.35 L/day, 11.7 L, and 27 days, respectively, for a typical 90-kg subject with psoriasis with an albumin level of 42 g/L, and 0.31 L/day, 8.45 L, and 22 days, respectively, for a typical 65-kg subject with Crohn’s disease with an albumin level of 37 g/L. Risankizumab absolute subcutaneous bioavailability and absorption rate constant were 72% and 0.18 day⁻¹, respectively. Inter-individual variability for clearance was 37%.

Conclusions

Risankizumab displayed pharmacokinetic characteristics typical for an IgG1 monoclonal antibody with no apparent target-mediated disposition. Accounting for the effects of body weight and baseline albumin explained the small differences in the pharmacokinetics of risankizumab between psoriasis and Crohn’s disease, with no further differences between the patient populations.

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Title: Population Pharmacokinetics of the Interleukin-23 Inhibitor Risankizumab in Subjects with Psoriasis and Crohn’s Disease: Analyses of Phase I and II Trials
Authors: Ahmed A. Suleiman
Amit Khatri
Mukul Minocha
Ahmed A. Othman
Publication date: 01-03-2019
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 3/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-018-0704-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Population Pharmacokinetics of the Interleukin-23 Inhibitor Risankizumab in Subjects with Psoriasis and Crohn’s Disease: Analyses of Phase I and II Trials

Abstract

Background and Objectives

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

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Abstract

Background and Objectives

Methods

Results

Conclusions

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