itraconazole

P1, N=36, Recruiting, Celgene | Not yet recruiting --> Recruiting

P1, N=50, Recruiting, DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company | Not yet recruiting --> Recruiting

P2, N=100, Not yet recruiting, AstraZeneca

P=N/A, N=200, Active, not recruiting, University of Rome Tor Vergata | Recruiting --> Active, not recruiting

P1, N=32, Recruiting, Celgene | Not yet recruiting --> Recruiting

P1, N=30, Recruiting, Bayer | Not yet recruiting --> Recruiting

P1, N=42, Not yet recruiting, Vertex Pharmaceuticals Incorporated

P1, N=48, Recruiting, Asceneuron S.A. | Not yet recruiting --> Recruiting

P1, N=14, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P1, N=75, Terminated, Celgene | Trial completion date: Sep 2025 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Mar 2024; Business objectives have changed

P1, N=36, Not yet recruiting, Celgene

P1, N=14, Not yet recruiting, AstraZeneca

P1, N=20, Completed, Shanghai Henlius Biotech | Not yet recruiting --> Completed | N=52 --> 20 | Trial primary completion date: Sep 2023 --> Dec 2023

P1, N=30, Not yet recruiting, Bayer

P1, N=72, Not yet recruiting, Jemincare

P1, N=28, Not yet recruiting, Shandong Suncadia Medicine Co., Ltd.

P1, N=50, Not yet recruiting, DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company

P1, N=60, Completed, Cerevel Therapeutics, LLC | Recruiting --> Completed

P1, N=28, Not yet recruiting, Shouyao Holdings (Beijing) Co. LTD

P3, N=700, Recruiting, Yale University | Trial completion date: Apr 2024 --> Apr 2027 | Trial primary completion date: Apr 2024 --> Apr 2027

In contrast, STING activation was enhanced when the lipid-shuttling protein OSBP, which removes PI4P from the Golgi apparatus, was inhibited by the US Food and Drug Administration-approved antifungal itraconazole...Furthermore, a mutant STING that could not bind to PI4P failed to traffic from the ER to the Golgi apparatus in response to a STING agonist, whereas forced relocalization of STING to PI4P-enriched areas elicited STING activation in the absence of stimulation with a STING agonist. Thus, PI4P is critical for STING activation, and manipulating PI4P abundance may therapeutically modulate STING-dependent immune responses.

P=N/A, N=223671, Active, not recruiting, University of California, San Francisco | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2025

P1, N=236, Recruiting, OrsoBio, Inc | N=156 --> 236 | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=32, Recruiting, Shenzhen TargetRx, Inc. | Not yet recruiting --> Recruiting

P=N/A, N=150, Not yet recruiting, First Hospital of China Medical University

P1, N=32, Not yet recruiting, Shenzhen TargetRx, Inc.

P2, N=68, Recruiting, Montreal Heart Institute | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

The impact of CYP3A4 inhibition was interrogated utilizing repeat doses of 200 mg of itraconazole, a strong CYP3A4 inhibitor, on 360 mg of sotorasib PKs. The impact of CYP3A4 induction was interrogated utilizing multiple doses of 600 mg of rifampin, a strong CYP3A4 inducer...OATP1B1/3 inhibition decreased sotorasib Cmax and AUCinf by 16% and 23%, respectively. These results support that sotorasib can be given together with strong CYP3A4 and OATP1B1/3 inhibitors but the co-administration of sotorasib and strong CYP3A4 inducers should be avoided.

P1, N=14, Completed, Shionogi | Active, not recruiting --> Completed

P1, N=142, Active, not recruiting, Amgen | Trial primary completion date: Jan 2024 --> Sep 2024

P=N/A, N=104, Recruiting, Postgraduate Institute of Medical Education and Research | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=144, Recruiting, Aligos Therapeutics | Trial completion date: Mar 2024 --> Jul 2024 | Trial primary completion date: Dec 2023 --> Apr 2024

P3, N=100, Active, not recruiting, Postgraduate Institute of Medical Education and Research | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

P1, N=48, Recruiting, TYK Medicines, Inc

P1, N=40, Completed, Suzhou Zelgen Biopharmaceuticals Co.,Ltd

P1, N=40, Recruiting, Emalex Biosciences Inc. | Not yet recruiting --> Recruiting

P1, N=60, Recruiting, Alexion Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting

Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans...Simulations using the developed model predicted that moderate CYP3A inhibitors (e.g., verapamil and diltiazem) may increase brigatinib AUC by ~40%, whereas moderate CYP3A inducers (e.g., efavirenz) may decrease brigatinib AUC by ~50%. Simulations of potential transporter-mediated DDIs predicted that brigatinib may increase systemic exposures (AUC ) of P-gp substrates (e.g., digoxin and dabigatran) by 15%-43% and MATE1 substrates (e.g., metformin) by up to 29%; however, negligible effects were predicted on BCRP-mediated efflux and OCT1-mediated uptake. The PBPK analysis results informed dosing recommendations for patients receiving moderate CYP3A inhibitors (40% brigatinib dose reduction) or inducers (up to 100% increase in brigatinib dose) during treatment, as reflected in the brigatinib prescribing information.

P1, N=48, Not yet recruiting, Asceneuron S.A.

P1, N=49, Completed, Guangdong Raynovent Biotech Co., Ltd | Recruiting --> Completed

Itraconazole inhibited cell glycolysis and tumor growth via the CEBPB-ENO1 axis. In this study, we illustrate a new energy metabolism mechanism for itraconazole on tumor growth in CRC that will provide a theoretical basis for CRC targeting/combination therapy.

P1, N=30, Completed, Eli Lilly and Company | Recruiting --> Completed