A phase I randomized, <scp>double‐blind</scp>, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects

Gu, Kenan; Ruff, Dennis; Key, Cassandra; Thompson, Marissa; Jiang, Shoshanna; Sandison, Taylor; Flanagan, Shawn D.

doi:10.1111/cts.13286

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…It should be noted that subcutaneous administration of rezafungin showed a pharmacokinetic profile with a long exposure period and did not result in serious adverse events, death, or withdrawal, which suggests a subcutaneous formulation could be considered at a future time. 17…”

Section: Pharmacokineticsmentioning

confidence: 99%

Formulary Drug Review: Rezafungin

Kessel,

Baker

2023

Hosp Pharm

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Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.

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Section: Pharmacokineticsmentioning

confidence: 99%

Formulary Drug Review: Rezafungin

Kessel,

Baker

2023

Hosp Pharm

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“…It inhibits beta‐1,3‐D glucan synthase, blocking the production of cell wall beta‐1,3‐D glucan 41 . A Phase 3 study of candidiaemia and invasive candidiasis has been completed (ReSTORE, NCT03667690), and a further Phase 3 study of invasive fungal infection is ongoing (ReSPECT, NCT04368559) 42,43 . It has broad activity against Candida spp.…”

Section: Current Drugs In the Antifungal Pipelinementioning

confidence: 99%

“… 41 A Phase 3 study of candidiaemia and invasive candidiasis has been completed (ReSTORE, NCT03667690), and a further Phase 3 study of invasive fungal infection is ongoing (ReSPECT, NCT04368559). 42 , 43 It has broad activity against Candida spp. as well as common dermatophytes.…”

Section: Current Drugs In the Antifungal Pipelinementioning

confidence: 99%

Antifungal chemotherapies and immunotherapies for the future

Armstrong‐James

2022

Parasite Immunology

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Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3‐beta‐D‐glucan‐approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro‐drug of manogepix, which targets glycosylphosphatidylinositol‐anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon‐γ and G‐CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti‐IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL‐4 and IL‐5 are being evaluated. In addition, T‐cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.

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A phase I randomized, double‐blind, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects

Ruff

Key

et al. 2022

Clinical Translational Sci

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Rezafungin is a novel echinocandin being developed for the treatment and prevention of invasive fungal infections. The objectives of this randomized, double-blind study in healthy adults were to determine the safety, tolerability, and pharmacokinetics of rezafungin after subcutaneous (s.c.) administration. The study design consisted of six sequential cohorts of eight subjects, except for the first cohort with four subjects. The subjects were randomized in a 3:1 ratio of rezafungin to placebo and were to receive a single dose of 1, 10, 30, 60, 100, or 200 mg. The most common adverse events (AEs) were increased alanine aminotransferase and sinus bradycardia (unsolicited) and erythema at the injection site (solicited).Unsolicited AEs were generally mild to moderate and not rezafungin-related.Although the study was terminated after the 10 mg dose cohort due to concerns of potential increased severity of injection site reactions, no predetermined dose escalation halting criteria were met. Following the 10 mg single s.c. dose of rezafungin (n = 6), the geometric mean (GM) maximum concentration (C max ) was 105.0 ng/ml and the median time to C max was 144 h. The GM area under the concentration-time curve was 32,770 ng*h/ml. The median estimated terminal half-life was 193 h. The GM apparent oral clearance was 0.255 L/h and the GM apparent volume of distribution was 68.5 L. This study demonstrates that a single s.c. dose of rezafungin in healthy adult subjects: (1) did not result in serious AEs, death, or withdrawal from the study due to an AE; and (2) produced a pharmacokinetic profile with long exposure period postadministration. In an effort to reduce the occurrence of injection site reactions, a re-evaluation of the rezafungin s.c. formulation could be considered in the future.How to cite this article: Gu K, Ruff D, Key C, et al. A phase I randomized, double-blind, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects.

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A phase I randomized, double‐blind, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects

Cited by 3 publications

References 8 publications

Formulary Drug Review: Rezafungin

Formulary Drug Review: Rezafungin

Antifungal chemotherapies and immunotherapies for the future

A phase I randomized, double‐blind, single subcutaneous dose escalation study to determine the safety, tolerability, and pharmacokinetics of rezafungin in healthy adult subjects

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