827. Safety, Tolerability, and Pharmacokinetics (PK) of Posaconazole (POS) Intravenous (IV) Solution and Oral Powder for Suspension in Children With Neutropenia
Session: Poster Abstract Session: Use of PK/PD to optimize existing antibiotics and antifungals
Thursday, October 5, 2017
Room: Poster Hall CD
Posters
  • ID Week_Groll_Poster 827.pdf (254.6 kB)
  • Background: POS, a triazole antifungal approved for prophylaxis and treatment of adults with invasive fungal infections, is available as an IV solution and 2 oral formulations: an oral suspension and a tablet with improved bioavailability. A novel powder for oral suspension (PFS) has been developed to offer the bioavailability of the tablet in a formulation optimized for weight-based dosing in children. The objective of this study is to evaluate the safety, tolerability, and PK of POS IV and POS PFS in pediatric patients (pts) aged 2 to 17 y with documented or expected neutropenia.  

    Methods: This is an ongoing, nonrandomized, multicenter, open-label, sequential dose-escalation study evaluating POS IV and POS PFS. Pts are divided into 2 age groups: 2 to <7 and 7 to 17 y. Each age group includes 2 dose cohorts: 3.5 mg/kg/d and 4.5 mg/kg/d. Pts received 10-28 d of POS initially as IV solution with the option to switch to PFS after 10 d for the remainder of the treatment period. PK sampling was conducted after 7-10 d on each formulation. Target PK exposure was ~90% of pts with Cavg 500-2500 ng/mL. Cavg is defined as AUC over a dosing interval.

    Results: 57 of 66 pts (86%) who received POS IV were PK evaluable; 35 pts (53%) received POS PFS, of whom 30 (86%) were PK evaluable. Table 1 shows Cavg and proportion in target range of PK-evaluable pts by dose cohort and age group. The safety profiles of POS IV and PFS were similar to those previously reported for adults treated with oral/IV POS.

    Conclusion: POS PFS resulted in lower POS exposure than IV across age groups at both dose levels. POS exposure was substantially lower in the younger age group for both IV and PFS. At 4.5 mg/kg, the pts in this study achieved the predefined target but did not achieve systemic exposures (mean Cavg) comparable to those seen in adults with POS IV or tablet. These results suggest that study of POS IV and PFS dosing >4.5 mg/kg/d is warranted.

     

    Andreas H. Groll, MD1, Hisham Abdel-Azim, MD, MS2, Thomas Lehrnbecher, MD3, William Steinbach, MD4, RoseAnn Murray, PhD5, Amanda Paschke, MD, MSCE5, Eric Mangin, MS5, Gregory A. Winchell, MD5 and Christopher J. Bruno, MD5, (1)Infectious Disease Research Program, Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster, Münster, Germany, (2)Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, (3)Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University of Frankfurt, Frankfurt, Germany, (4)Pediatric Infectious Diseases, Duke University Hospital, Durham, NC, (5)Merck & Co., Inc., Kenilworth, NJ

    Disclosures:

    A. H. Groll, Merck Sharp & Dohme: Consultant , Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium

    H. Abdel-Azim, None

    T. Lehrnbecher, Merck/MSD: Scientific Advisor and Speaker's Bureau , Speaker honorarium
    Astellas: Scientific Advisor and Speaker's Bureau , Speaker honorarium
    Basilea: Scientific Advisor , Consulting fee
    Gilead: Investigator , Scientific Advisor and Speaker's Bureau , Research grant and Speaker honorarium
    Pfizer: Speaker's Bureau , Speaker honorarium

    W. Steinbach, Merck: Consultant , Consulting fee
    Astellas: Consultant , Consulting fee
    Gilead: Consultant , Consulting fee

    R. Murray, Merck: Employee , Salary

    A. Paschke, Merck: Employee , Salary

    E. Mangin, Merck: Employee , Salary

    G. A. Winchell, Merck: Research Contractor , Consulting fee

    C. J. Bruno, Merck: Employee and Shareholder , Salary and Stock

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.