Phase 1B Study of the Pharmacokinetics (PK) and Safety of Posaconazole (POS) IV in Patients (Pts) at Risk for Invasive Fungal Infection (IFI)

Ref ID: 18780

Author:

J. Maertens, MD – Prof 1, O. Cornely, MD – Prof 2, A. Ullmann, MD – Head Infect Dis 3, W. Heinz, MD – Prof 4, G. Krishna, PhD – Dir 5, M. Caceres, MS – Scientist II 5, N. Kartsonis, MD – Sect Hd, HIV, Antibacterials, Antifungals; Exec Dir, Clin Res,

Author address:

1Univ Hosp Gasthuisberg, Leuven, Belgium, 2Univ Hosp Cologne, Cologne, Germany, 3Johannes Gutenberg Univ, Mainz, Germany, 4Julius-Maximilians-Univ Würzburg, Würzburg, Germany, 5Merck, Whitehouse Station, NJ.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: POS IV solution is a new POS formulation intended to assure adequate exposure among pts unable to tolerate/absorb oral POS. POS IV may be beneficial in IFI prevention and treatment in neutropenic pts following chemotherapy, or in pts with graft vs host disease after stem cell transplantation. A 2-part study (Phase 1B/3) was conducted to evaluate the PK and safety of POS IV when given to pts as antifungal prophylaxis. The Phase 1B objective was to identify a POS dose that attained a prespecified exposure target to be further studied in a more diverse population in Phase 3. Methods: Phase 1B was a dose ranging multicenter PK and safety study in subjects with neutropenia due to chemotherapy. There was 1 single dose and 2 multiple dose cohorts. In the single dose cohort, safety and tolerability of a single dose of POS IV 200 mg (n=10) was compared to placebo (n=11). Subsequently 2 doses were evaluated: POS IV 200 mg once daily (QD) (n=21), or 300 mg QD (n=24); all subjects received twice daily (BID) POS IV on day 1, followed by 13 additional days of POS IV, then POS oral suspension 400 mg BID for 14 days. The primary PK parameter of interest was steady state (day 14) average concentration (Cavg). The desired steady state exposure targets were Cavg ≥ 500 and 8804;2500 ng/mL in ≥ 90% of subjects. Results: The percentage of subjects attaining the steady state exposure target was 94% for 200 mg POS QD and 95% for 300 mg POS QD. Mean day 14 Cavg was 1180 ng/mL (mean Cmax 1950 ng/mL) and 1430 ng/mL (mean Cmax 2610 ng/mL) for the 200 mg and 300 mg dosing cohorts, respectively. POS IV was well tolerated with a safety profile similar to that previously reported for POS oral suspension. Conclusions: POS IV was well tolerated and attained the prespecified PK exposure target at 200 and 300 mg QD; 300 mg QD was selected for the Phase 3 study segment.

Abstract Number: A-1946a

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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