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Clinical Pharm in Drug Dev - 2023 - Polasek - Safety Tolerability and Pharmacokinetics of IMU‐935 a Novel Inverse302.85 kB
Published VersionCC BY V4.0, Open Access
Journal article
Safety, Tolerability, and Pharmacokinetics of IMU-935, a Novel Inverse Agonist of Retinoic Acid Receptor-Related Orphan Nuclear Receptor γt: Results From a Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study
Clinical Pharmacology in Drug Development, Vol.12(5), pp.525-534
2023
PMID: 36938862
Abstract
Retinoic acid receptor-related orphan nuclear receptor (ROR)γt regulates the transcription of interleukin-17 and other cytokines implicated in inflammatory and autoimmune diseases. We assessed the safety, tolerability, and pharmacokinetics (PK) of IMU-935, an inverse agonist of RORγt, in a first-in-human phase 1 study. This was a double-blind, placebo-controlled trial that randomly assigned healthy subjects single ascending doses (25-400 mg) or multiple ascending doses (150 mg once or twice daily for 14 days) of IMU-935 or placebo. Dose escalation was determined by the safety, tolerability, and PK. Twenty-four and 70 subjects received placebo or IMU-935, respectively. Of the 70 subjects who received IMU-935, 59 received a single dose and 11 received multiple doses. Treatment-emergent adverse events (TEAEs) occurred in 21 subjects (88%) and 58 (83%) given any dose of placebo or IMU-935, respectively. Treatment-related TEAEs occurred in 6 (30%) and 25 (42%) subjects given a single dose of placebo and IMU-935, respectively. All treatment-related TEAEs were mild except for 2 moderate TEAEs and 1 moderate TEAE in the IMU-935 group and placebo group, respectively. No treatment-related discontinuations or serious adverse events occurred. The PK of IMU-935 were dose proportional with a half-life of ≈24 hours. In conclusion, IMU-935 was safe with no dose-limiting toxicities and had a PK profile that supports once-daily dosing.
Details
- Title
- Safety, Tolerability, and Pharmacokinetics of IMU-935, a Novel Inverse Agonist of Retinoic Acid Receptor-Related Orphan Nuclear Receptor γt: Results From a Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study
- Authors
- Thomas M Polasek (Corresponding Author) - CMAX Clinical Research (Australia)Indika Leelasena (Author) - University of the Sunshine Coast, Queensland, UniSC Clinical Trials CentreIrina Betscheider (Author) - Immunic AGMarija Marolt (Author) - Immunic AGHella Kohlhof (Author) - Immunic AGDaniel Vitt (Author) - Immunic AGFrank Fliegert (Author) - Immunic AGAndreas R Muehler (Author) - Immunic AG
- Publication details
- Clinical Pharmacology in Drug Development, Vol.12(5), pp.525-534
- Publisher
- Wiley-Blackwell Publishing Ltd.
- Date published
- 2023
- DOI
- 10.1002/cpdd.1243
- ISSN
- 2160-7648; 2160-763X
- PMID
- 36938862
- Copyright note
- © 2023 Immunic AG. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Organisation Unit
- UniSC Clinical Trials Centre; Office of the Deputy Vice-Chancellor (Research and Innovation); School of Law and Society
- Language
- English
- Record Identifier
- 99716032902621
- Output Type
- Journal article
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