Disposition, demographics, and exposure.
candidemia, death, ≤28
CANDIDEMIA, ACUTE MYELOID LEUKEMIA
The study enrolled 9 participants from 2 sites in South Africa (15 participants were planned for enrollment). However, the study was terminated early due to the impact of the COVID-19 pandemic on patient enrollment. The intent-to-treat and safety populations each included all 9 enrolled participants with candidemia (henceforth, study population). Eight participants completed a full course of treatment, and one did not complete treatment due to death. Seven participants completed the study through the 4-week follow-up, with an additional death reported during the follow-up period.Demographics and baseline characteristics for enrolled participants were consistent with the epidemiology of Demographics and baseline characteristicsSD, standard deviation.yrs, years.BMI, body mass index.APACHE, acute physiology and chronic health evaluation.ICU, intensive care unit.The mean (SD) duration of treatment with FMGX was 19 (5.83) days, ranging from 11 to 27 days; most participants (5/9 [55.6%]) received FMGX for >14 days but ≤28 days. All participants received FMGX via IV infusion; none were switched to the oral formulation. PK sampling was sparse and relatively few PK samples were collected, precluding a model-based compartmental analysis. However, a linear, two-compartment population PK model-based on previous phase I studies provided an adequate fit for the MGX concentrations observed. The PK data collected indicated that all participants had systemic exposures to MGX (median [range] total drug plasma AUC over duration of therapy: 93 [64.4 to 182] mg·h/L), consistent with prior exposure data from Phase 1 and Phase 1b studies in healthy volunteers and in patients with acute myeloid leukemia. MGX AUC:MIC ratios were also determined (median [range] total drug plasma AUC:MIC ratio over duration of therapy: 7147 [5194 to 12112] mg · h/L). Attainment of the total-drug plasma AUC:MIC ratio ED