1839. A Phase 1 Study to Assess the Pharmacokinetics of Sulopenem Etzadroxil (PF-03709270)
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • Poster 1839 - Interium 75 x 45_PROOF.pdf (2.6 MB)
  • Background: Sulopenem etzadroxil is a pro-drug of sulopenem (CP-70,429) designed to enhance its bioavailability. A Phase 1 study was performed to evaluate the effect of food and probenecid on the pharmacokinetics, safety and tolerability of sulopenem etzadroxil

    Methods:

    This study is a randomized, double blinded (investigator and subject blinded, sponsor-open), placebo-controlled, multiple dose study in healthy volunteers of PF-03709270, with or without co-administration of probenecid, in fed or fasted state. Subjects were dosed twice a day for 6 days and once on Day 7. For the treatment groups dosed in the fed state, subjects were dosed approximately 30 minutes after the start of their meal. Pharmacokinetic sampling was done in 8 subjects per treatment group.

    Results:

    Treatment

    Fed / Fasted

    Descriptive

    Statistic

    Parameter (Day 1)

    Cmax

    (ng/mL)

    AUCTAU

    (hr*ng/mL)

    T>MIC (0.5µg/ml)

    [hr]

    T> MIC

    (0.5 µg/ml)

    [%]

    500 mg PF-03709270

    Fasted

    Mean

    1770.000

    3683.093

    2.660

    22.2

    SD

    529.474

    728.892

    Median

    1720.00

    3478.43

    CV%

    29.9

    19.8

    15.0

    500 mg PF-03709270

    Fed

    Mean

    1869.875

    4545.342

    3.127

    26.1

    SD

    741.019

    1131.901

    Median

    1725.00

    4509.96

    CV%

    39.6

    24.9

    27.9

    500 mg PF-03709270 + 500 mg probenecid

    Fasted

    Mean

    1773.750

    3952.865

    3.063

    25.5

    SD

    465.463

    893.698

    Median

    1830.00

    4238.98

    CV%

    26.2

    22.6

    23.2

    500 mg PF-03709270 + 500 mg probenecid

    Fed

    Mean

    1690.000

    6396.538

    5.364

    44.7

    SD

    576.517

    1415.977

    Median

    1500.00

    6301.46

    CV%

    34.1

    22.1

    41.9

    Conclusion: Both food and probenecid increase the absorption of PF-03709270 and consequently serum levels of sulopenem. The combination of food and probenecid further increases serum exposures of sulopenem. Probenecid, food, or the combination of both, all significantly prolong the T>MIC for sulopenem. These data will help inform PKPD modelling in selection of a dose for Phase 3 studies.

    Michael Dunne, MD1, Elise Dunzo, Ph.D2 and Sailaja Puttagunta, MD1, (1)Iterum Therapeutics, Old Saybrook, CT, (2)Parexel International, Baltimore, MD

    Disclosures:

    M. Dunne, Iterum Therapeutics: Employee and Shareholder , Salary

    E. Dunzo, None

    S. Puttagunta, Iterum Therapeu: Employee and Shareholder , Salary

    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.