768. Evaluation of the pharmacokinetics of GS-5806 in healthy Japanese and Caucasian subjects
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Posters
  • Bio Xin Ethnicity IDWeek.pdf (88.7 kB)
  • Background: GS-5806 is an oral antiviral fusion inhibitor under clinical evaluation to treat RSV infections. The purpose of this study was to evaluate the pharmacokinetics (PK) and safety of GS-5806 in healthy Japanese and Caucasian subjects, and to evaluate the potential food effect of on GS-5806 PK.

    Methods: Eligible healthy first generation Japanese (n = 15) and Caucasian (n = 16) subjects received a single oral dose of 200 mg GS-5806 on Day 1 (fasted). Caucasian subjects received a second dose of 200 mg GS-5806 on Day 13 with a high-fat breakfast (fed). Serial blood samples were collected for up to 120 hrs postdose and plasma concentrations of GS-5806 were determined. An analysis of variance was fitted to the log transformation of PK parameters (Cmax and AUCinf) and included ethnicity or food as a fixed effect. SAS Proc Mixed procedure was used to calculate the ratio of geometric least squares means (GLSM) and 90% confidence interval (CI) of PK parameters between ethnic groups and feeding conditions. Safety was monitored throughout the study.

    Results: Following a single oral dose of 200 mg GS-5806, the plasma exposures (Cmax and AUCinf), time to peak concentrations, and half-life were similar between Japanese and Caucasian subjects, and between subjects who were fed and fasted (Table 1). All adverse events were Grade 1 in severity. No notable differences with regards to laboratory findings, vital signs, or other safety evaluations were observed between Japanese and Caucasian subjects, or between fed and fasted conditions.

    Table 1. PK results of GS-5806

     

    Mean (%CV)

    % GLSM Ratio (90% CI)

    Parameters

    Japanese, fasted
    (N = 15)

    Caucasian, fasted
    (N = 16)

    Caucasian, fed (n=16)

    Japanese vs. Caucasian (fasted)

    Fed vs. Fasted (Caucasian)

    AUCinf (ng•h/mL)

    68300 (24.1)

    71500 (26.5)

    68500 (23.01)

    96.0 (83.5, 110)

    96.1 ( 90.6, 102)

    Cmax (ng/mL)

    1930 (23.0)

    1960 (21.0)

    1890 (22.6)

    98.3 (87.1, 111)

    96.0 ( 88.2, 104)

    Tmax (h)a

    3.00 (3.00, 4.00)

    3.00 (2.00, 3.00)

    2.52 (2.00, 4.00)

    -

    -

    t1/2 (h) a

    30.9 (29.6, 33.1)

    32.4 (30.1, 36.0)

    33.8 (31.9, 37.8)

    -

    -

    a.         Median (Q1, Q3)

    Conclusion: There were no differences for GS-5806 PK between Japanese and Caucasian subjects and no dose modifications are needed for Japanese subjects. Due to the lack of a food effect on GS-5806 PK, GS-5806 can be taken without regard to food.

    Yan Xin, Ph.D., Seth Toback, M.D., Winnie Weng, PhD, PJ Costales, BA, Jason Chien, M.D., Jeffrey Silverman, PhD and Srini Ramanathan, PhD, Gilead Sciences, Inc., Foster City, CA

    Disclosures:

    Y. Xin, Gilead Sciences: Employee and Shareholder , Salary

    S. Toback, Gilead Sciences: Employee and Shareholder , Salary

    W. Weng, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    P. Costales, Gilead Sciences, Inc: Employee and Shareholder , Salary

    J. Chien, Gilead Sciences: Employee and Shareholder , Salary

    J. Silverman, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    S. Ramanathan, Gilead Sciences: Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.