Phase 1B Study of the Pharmacokinetics and Safety of Posaconazole (POS) Solid Oral Tablet in Patients at Risk for Invasive Fungal Infection (IFI)

Ref ID: 18770

Author:

R. F. Duarte, MD, PhD – Director of BMT Programme1, J. López Jiménez, MD, PhD – Head of Clinical Hematology 2, O. A. Cornely, MD – Professor of Medicine, Senior Physician 3, L. Ma, PhD – Clinical PK/PD Scientist 4, M. P. S. van Iersel, PhD – Lead Cli

Author address:

1Catalan Inst Oncol, Barcelona, Spain, 2Hosp Ramon y Cajal, Madrid, Spain, 3Univ Hosp Cologne, Cologne, Germany, 4Merck, Titusville, NJ, 5MSD, Oss, Netherlands, 6Merck, Whitehouse Station, NJ.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: POS solid oral tablet is a new formulation providing systemic absorption of POS in the gastrointestinal tract regardless of food intake. This formulation may be beneficial in prevention/treatment of IFI in patients with poor oral intake following chemotherapy or bone marrow transplant. A 2-part study (phase 1B/3) was conducted to evaluate the PK and safety of POS tablet when given as antifungal prophylaxis. The objective of phase 1B was to identify a POS dose that attained a prespecified exposure target for further study in a more diverse population in part 2 (phase 3). Methods: Phase 1B was a dose-ranging multicenter PK and safety study in 51 subjects with acute myeloid leukemia/myelodysplasia at high risk for IFI. The 2 POS solid oral tablet dosing cohorts were 200 mg once daily (QD) (n = 19) and 300 mg QD (n = 32) taken during the neutropenic period for a maximum of 28 days. Both cohorts had twice-daily (BID) loading doses on day 1. The primary PK parameter of interest was steady-state (day 8) average concentration (Cavg). The desired exposure target was steady-state Cavg ≥ 500 and 8804;2500 ng/mL in ≥ 90% of subjects. Results: The percentage of subjects attaining the day 8 exposure target was 79% for POS 200 mg QD and 97% for POS 300 mg QD. Mean day 8 Cavg was 951 ng/mL (mean Cmax 1270 ng/mL) for POS 200 mg QD and 1460 ng/mL (mean Cmax 1960 ng/mL) for POS 300 mg QD. POS tablet was well tolerated; safety profile was similar to that previously noted for POS oral suspension. Conclusions: This new formulation of POS solid oral tablet 300 mg QD taken without regard to food attained the prespecified PK exposure target in ≥ 90% of subjects. Therefore, 300 mg QD was selected as the dose for the phase 3 study segment, to be further studied in a more diverse patient population.

Abstract Number: A-1934

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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