rifampicin

P2, N=1500, Not yet recruiting, AIDS Clinical Trials Group | Trial completion date: Dec 2028 --> Apr 2029 | Initiation date: Apr 2024 --> Oct 2024 | Trial primary completion date: Dec 2028 --> Apr 2029

Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively)...Safety findings were mild in this short-term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments.

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

In this way, an association between ABCC2 protein levels and transporter activity in HepG2 cells treated with rifampicin and hypericin and their derived EVs was observed...An analysis of plasma EVs from healthy volunteers confirmed, for the first time at the protein level, the presence of both transporters in more than half of the samples. Our findings support the potential of analyzing ABC transporters, and especially ABCC2, in EVs to estimate the transporter expression in HepG2 cells.

P1, N=56, Completed, Guangdong Raynovent Biotech Co., Ltd | Recruiting --> Completed

Seaweed derived carrageenan/ZM/agarose hydrogel was successfully prepared (@5 : 5 wt%) and was seen to support the growth of L929 cells (1 × 105 cells per mL) and have a higher swelling (≈250-280%). This study indicates that ZM-based hydrogel could be a potential drug carrier (Rifampicin and Levofloxacin) for targeting tumour-associated macrophages (M2).

P1, N=36, Not yet recruiting, Celgene

P2, N=93, Completed, Bill & Melinda Gates Medical Research Institute | Phase classification: P2a --> P2

P1, N=50, Not yet recruiting, University of Otago | Phase classification: P --> P1 | N=25 --> 50

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

P1, N=72, Not yet recruiting, Jemincare

P2, N=122, Active, not recruiting, Centre for the AIDS Programme of Research in South Africa | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2024 | Trial primary completion date: Jul 2024 --> Jan 2024

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

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

The second generation D-peptide AlF-NOTA-2xDV1(c11sc12s) showed high affinity for human CXCR4 and the corresponding radiotracer was produced in good radiochemical yields. However, [18F]AlF-NOTA-2xDV1(c11sc12s) is not specific for CXCR4 and is also a substrate for OATP1B1 and/or OATP1B3, known to mediate hepatic uptake. Therefore, D-amino acid peptides, based on the viral macrophage inflammatory protein II, are not the prefered vector molecule for the development of CXCR4 targeting molecular imaging tools.

P1/2, N=200, Not yet recruiting, University of Virginia

P3, N=186, Recruiting, Beijing Chest Hospital | Not yet recruiting --> Recruiting

P2, N=122, Recruiting, Centre for the AIDS Programme of Research in South Africa | Active, not recruiting --> Recruiting | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Jul 2024

DDIs involving imatinib and NDMI were simulated with perpetrator drugs rifampicin, ketoconazole, and gemfibrozil as well as victim drugs simvastatin and metoprolol. Overall, 12/12 predicted DDI area under the curve determined between first and last plasma concentration measurements (AUClast ) ratios and 12/12 predicted DDI maximum plasma concentration (Cmax ) ratios were within twofold of the respective observed ratios. Potential applications of the final model include model-informed drug development or the support of model-informed precision dosing.

P3, N=235, Not yet recruiting, Centre Hospitalier Universitaire de Nice | Initiation date: Jul 2023 --> Mar 2024

P2, N=80, Recruiting, University of Cape Town | Trial completion date: Oct 2025 --> Feb 2026 | Trial primary completion date: Oct 2024 --> Sep 2025

The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38...Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.

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=18, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

P2, N=128, Recruiting, GlaxoSmithKline | N=70 --> 128

P2, N=122, Active, not recruiting, Centre for the AIDS Programme of Research in South Africa | Recruiting --> Active, not recruiting | Phase classification: P2b --> P2 | Trial completion date: Dec 2024 --> Aug 2024 | Trial primary completion date: Jul 2024 --> Jan 2024

P1/2, N=84, Active, not recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting --> Active, not recruiting

P1, N=32, Completed, Bellus Health Inc. - a GSK company | Not yet recruiting --> Completed

P3, N=164, Recruiting, Radboud University Medical Center | Not yet recruiting --> Recruiting

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

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

Out of 44 known ADME proteins in plasma EVs, previously annotated mouse cytochrome P450 3A11 (Cyp3a11), homolog to human CYP3A4, and uridine 5'-diphospho (UDP) glucuronosyltransferase 2A3 (Ugt2a3), increased upon daily rifampicin dosage. Dasatinib, a tyrosine kinase inhibitor to treat leukemia, also elevated Cyp3a11 levels in plasma EVs, but to a lesser extent. Altogether, this study demonstrates that measuring drug enzymes in circulating EVs as an effective surrogate is highly feasible and may transform today's drug discovery and development for personalized medicine.

P1, N=40, Recruiting, Emalex Biosciences 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.

P2, N=156, Recruiting, Brigham and Women's Hospital | Not yet recruiting --> Recruiting

P1, N=18, Completed, Dong-A ST Co., Ltd. | Recruiting --> Completed

P1, N=18, Active, not recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Active, not recruiting

P=N/A, N=4200, Active, not recruiting, Foundation for Innovative New Diagnostics, Switzerland | Recruiting --> Active, not recruiting

P2, N=1500, Not yet recruiting, AIDS Clinical Trials Group

P1, N=64, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024

P1, N=18, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.

P1, N=40, Not yet recruiting, Emalex Biosciences Inc.