Noxafil (posaconazole)

P1/2, N=260, Recruiting, BeiGene | Phase classification: P1b/2 --> P1/2 | Trial completion date: Aug 2025 --> Feb 2028 | Trial primary completion date: Dec 2023 --> Feb 2028

The results showed that allometric scaling, ABCB1-rs1128503 genotype, and posaconazole (POS) significantly improved the PopPK model fit...No significant effects on VIPN were observed for CYP3A5 (rs776746), CYP3A4 (rs2242480), CEP72 (rs924607), or various ABCB1 variants (rs1128503, rs2032582, rs1045642, rs4728709, rs4148737, and rs10276036), nor with the co-administration of fluconazole or dasatinib. In summary, co-administration of POS increased VCR exposure by 0.4-fold and raised the risk of VIPN, with an occurrence probability generally exceeding 0.7. Therapeutic drug monitoring of VCR in clinical practice may be necessary to enable appropriate dose adjustments and individualized treatment.

P2, N=50, Recruiting, Post Graduate Institute of Medical Education and Research, Chandigarh | N=30 --> 50 | Trial completion date: Jun 2024 --> Jul 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=60, Not yet recruiting, The First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital); Department of Hematology of Anhui Provinci

P=N/A, N=15, Not yet recruiting, Peking University People's Hospital

Azoles given concurrently or sequentially with midostaurin were found to be equally safe and effective in the treatment of newly diagnosed FLT3 AML. Additional confirmatory studies are needed due to our limited sample size.

P2, N=30, Not yet recruiting, Nantes University Hospital

P1, N=36, Completed, Zenith Technology Corp Ltd | Not yet recruiting --> Completed

P=N/A, N=55, Recruiting, Universitaire Ziekenhuizen KU Leuven | Unknown status --> Recruiting | Trial primary completion date: Mar 2015 --> Mar 2025

Interestingly, the mycobiome resistance patterns obtained against different classes of fungal antibiotics including azole (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and ketoconazole), echinocandin (anidulafungin, caspofungin and micafungin) and polyene (amphotericin B) drugs proved the prevalence of antibiotic resistance among the mycobiome of refinery industry in Saudi Arabia is relatively low...It showed the highest bioremoval capacity ranging from 85.72 % to 100.0 % against numerous pollutants found in a wide array of industrial effluents, including diclofenac, ibuprofen, carbamazepine, acetaminophen, sulfamethoxazole, bisphenol, bleomycin, vincristine, dicofol, methyl parathion, atrazine, diuron, dieldrin, chlorpyrifos, profenofos and phenanthrene...Enhancing the bioremoval efficiency of heavy metals from actual refining wastewater involves optimizing process parameters. The parameters optimized were the contact time, the fungal biomass dosage, pH, temperature and agitation rate.

P=N/A, N=30, Enrolling by invitation, Beijing Tsinghua Chang Gung Hospital

P3, N=600, Recruiting, Mundipharma Research Limited | Trial completion date: Aug 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Dec 2025

P1, N=10, Recruiting, Milton S. Hershey Medical Center | Trial completion date: May 2024 --> Jan 2025 | Trial primary completion date: May 2024 --> Dec 2024

P3, N=66, Terminated, Erasmus Medical Center | N=650 --> 66 | Trial completion date: Dec 2026 --> May 2024 | Recruiting --> Terminated | Trial primary completion date: Aug 2026 --> May 2024; futility

P2, N=20, Completed, Seoul National University Hospital | Unknown status --> Completed | N=40 --> 20 | Trial completion date: Jun 2020 --> Jul 2023 | Trial primary completion date: Jun 2019 --> Jul 2023

P=N/A, N=249, Completed, Medical University of Graz | Recruiting --> Completed | Trial completion date: Dec 2022 --> Aug 2023 | Trial primary completion date: Sep 2022 --> Aug 2023

P1, N=30, Not yet recruiting, University Health Network, Toronto | Trial completion date: Aug 2022 --> Jun 2027 | Trial primary completion date: Aug 2022 --> Jun 2025

This study demonstrated that concomitant ivosidenib significantly reduced posaconazole and voriconazole levels. Voriconazole should be avoided, empiric high-dose posaconazole (>300 mg/day) may be considered, and therapeutic drug monitoring is recommended in all patients receiving concomitant ivosidenib.

P2, N=31, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | Trial completion date: Apr 2024 --> Dec 2023 | Trial primary completion date: Apr 2024 --> Dec 2023

The combination of venetoclax (VEN) with either azacitidine (AZA) or decitabine (DEC) has shown promising results in older or unfit patients with AML and is now being investigated in younger patients as well...The dose of VEN was reduced to 20mg when administered with voriconazole or posaconazole or 100mg when administered with fluconazole or isavuconazium...GVHD prevention consisted of tacrolimus and methotrexate in 14 patients and post-transplant cyclophosphamide-based in 5 patients... Our preliminary data suggests that the combination of low-dose DEC plus VEN is a safe and potentially effective strategy to reduce the risk of post-SCT relapse. Adverse effects mainly included manageable cytopenias with no increase in risk of GVHD. The efficacy of the combination appears to be promising but needs longer follow-up as well as confirmation in large, randomized studies.

According to EORTC criteria, two patients (10%) had a probable IFI on day 14, and antifungal therapy with liposomal amphotericin B was started [3]...Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia... Twenty patients were included: 9 were women (45%) with a median age of 67 years old (±10. 5) and a median Charlson Comorbidity Index of 5 (±1. 3).

It is imperative to acknowledge the potential drug-drug interactions mediated by CYP3A4 between azoles and lenvatinib, as these interactions hold significant implications for their clinical utilization.

We observed three cases of invasive fungal infections (8.5%), once again with no differences between the two groups. Our study suggest that the concomitant administration of PCZ and midostaurin results effective and safe for FLT3-mut AML patients.

P1/2, N=17, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Nov 2023 | Trial primary completion date: Nov 2024 --> Nov 2023

Prophylactic oral levofloxacin and posaconazole were administered from day 8 through whole myelosuppression period of every cycles. MVHO therapy was effective and reasonably well tolerated in pediatric patients with refractory or relapsed AML, suggesting that it may comprise a suitable first-line treatment option for pediatric AML patients.

Treatment: First line IC was cytarabine 200 mg/m² d1-7 with idarubicin 9mg/m²/d1-5 or daunorubicin 90mg/m²/d1-3 in pts 18-60y or cytarabine 100 mg/m² d1-7 with idarubicin 8mg/m²/d1-5 and lomustine 200 mg/m²/d1 in pts > 60y...Midostaurin was added in FLT3-mutated pts...During first cycle of VEN/AZA, 12, 5 and 5 pts received 14, 21 or 28 days venetoclax, respectively; 19 were treated as out-pts, 4 received posaconazole and GCSF was used in 11 pts... In the setting of molecular relapse, VEN/AZA is safe, prevent overt relapse, and induce a high rate of molecular response before alloHCT. Molecular relapse becomes a major therapeutic challenge. Clinical trial endpoints should include the treatment of molecular relapse as an event for RFS and EFS estimation.

Adjustments to the VEN dose were made for patients concurrently receiving posaconazole. V-FLAI demonstrated remarkable efficacy without any safety concerns. Impressive CCR rate and MRD-negativity qualify the combination for randomized comparisons . A virtual-randomized phase 3 trial is currently being prepared.

ASTX727 (decitabine/ cedazuridine) was administered at 35 mg/100 mg PO daily days 1-5, venetoclax at 400 mg (target dose) PO daily days 1-14, and revumenib 113 mg PO Q12h (dose level [DL] 0) or 163 mg PO Q12h (DL 1, used in phase II monotherapy), days 1-28 with either posaconazole or voriconazole (strong CYP3A4 inhibitors, for antifungal prophylaxis). Early results indicate acceptable safety and high efficacy of this combination in R/R myeloid leukemias with either KMT2Ar or NPM1mt or NUP98r. This study is ongoing with plans to establish the recommended phase 2 dose and optimize delivery of this combination.

P4, N=24, Recruiting, Cedars-Sinai Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=30, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

The most frequently reported treatment-related AEs were erythema (n=14; 88%) and headache (n=11; 69%) in Part 1 and headache (n=7; 44%) in Part 2. The results of this study indicate that coadministration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided.

Amphotericin B, posaconazole, and voriconazole were successively used for antifungal therapy. Early diagnosis and treatment should be carried out. Combined antifungal therapy is recommended, and surgery is helpful to improve the patient's condition.

The drug clearance process was influenced by crucial covariates, namely creatinine clearance (CLCR) and concomitant posaconazole (POS). Empirical therapy would benefit from utilizing higher dosages and extended infusion durations. Therefore, it is suggested that patients with symptoms that are strongly suspected of Pseudomonas aeruginosa or Acinetobacter baumannii infections may be suitable for combined treatment with other antibacterial drugs.

BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.

Those who are intolerant to L-AmB can choose intravenous formulations or tablets of isavuconazole or posaconazole. Patients who are refractory to monotherapy can turn to combined antifungals therapy.

In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, P = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.

Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

As the validated agent for the treatment of chronic myelogenous leukemia (CML), flumatinib is a novel oral tyrosine kinase inhibitor (TKI) with higher potency and selectivity for BCR-ABL1 kinase compared to imatinib...Moreover, ketoconazole, posaconazole, and isavuconazole showed more potent inhibitory effects than itraconazole, fluconazole, and voriconazole on HLM-mediated flumatinib metabolism...According to the results of in vitro and in vivo studies, the metabolism of flumatinib was inhibited by isavuconazole, suggesting that isavuconazole may raise the plasma concentration of flumatinib. Thus, it is important to take special care of the interactions between flumatinib and isavuconazole in clinical applications.

Eleven patients diagnosed with acute leukemia who received azacitidine (AZA) and venetoclax (VEN) therapy for induction, reinduction, and salvage therapy were evaluated...Eight patients received posaconazole for primary antifungal prophylaxis and 2 patients for secondary antifungal prophylaxis...In this patient, facial swelling occurred on the 18th day, and liposomal amphotericin b was used due to possible IFI... 11 patients (n:11), 5 females (45.4%) and 6 males (54.5%), were included in this study and the median age was 62 years (range: 33 - 85). Demographic data and characteristics of the patients are given in Table 1. İn this period, the median follow-up duration was 28 days (range: 24 - 71).

Due to no difference in incidence, patient specific factors such as concomitant medications and baseline QTc should influence the choice between prophylactic agent.