The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future.

Phase 0 microdosing studies were introduced to the drug development community approximately 20 years ago. A microdose is defined as less than 1/100th of the dose calculated based on animal data to yield a pharmacological effect in humans, with a maximum of 100 μg, or 30 nmoles for protein products. In our experience, Phase 0 microdose studies have not been fully embraced by the pharmaceutical industry.

Pharmacokinetics, safety, and tolerability of fosmanogepix IV to oral switch and multiple IV doses in healthy participants.

Fosmanogepix [FMGX, APX001; active form: manogepix (MGX), APX001A] is a first-in-class, intravenous (IV)/oral antifungal currently being evaluated for invasive fungal disease treatment. Data from two phase 1, placebo-controlled studies [IV-oral switch (study 1) and multiple IV doses (study 2)] evaluating FMGX tolerability, and pharmacokinetics (PK) are presented. Healthy adults (study 1: 18-65 years; study 2: 18-55 years) were eligible (randomized 3:1 to FMGX: placebo).

Rethinking, reducing, and refining the classical oral tyramine challenge test of monoamine oxidase (MAO) inhibitors.

The oral tyramine challenge evaluates the safety of novel monoamine oxidase (MAO) inhibitors when taken with tyramine-containing food or drinks. In its current design, it comprises an extensive series of tyramine escalation steps until a blood pressure threshold is met. Due to the high variation in tyramine bioavailability, and thereby in blood pressure effect, this classical design has various limitations, including safety concerns.

Safety and Pharmacokinetics of Intravenous and Oral Fosmanogepix, a First-in-Class Antifungal Agent, in Healthy Volunteers.

Fosmanogepix (FMGX, APX001), a first-in-class, intravenous (i.v.) and oral (p.