901. Outcomes of Ceftolozane/tazobactam (C/T) in Patients With Moderate Renal Impairment in Two Phase 3 Trials for the Treatment of Complicated Intra-abdominal Infection (cIAI) and Complicated Urinary Tract Infection (cUTI)
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 101102179_Renal_Impair_L2c.pdf (372.3 kB)
  • Background: C/T, a novel antibacterial with activity against Gram-negative pathogens, is approved for treatment of cIAI and cUTI. In this analysis, outcomes in patients (pts) with moderate renal impairment (MRI) in Phase 3 trials were evaluated.

    Methods: Pts with cIAI received IV C/T plus metronidazole (MTZ) or meropenem (MEM); pts with cUTI received IV C/T or levofloxacin (LVX). C/T dose regimens by CrCL were 1.5 g q8h (≥50 mL/min) and 750 mg q8h (>30-<50 mL/min). Dose adjustments in comparator arms were according to prescribing information. Outcomes were determined 24-32 days after start of treatment and 7 days post treatment in the cIAI and cUTI studies, respectively.

    Results: Across all treatment arms response rates were lower in pts with MRI (CrCL >30-<50 mL/min) compared to those with CrCL ≥50 mL/min (Table). In micro intent to treat (MITT) analyses, where pts with indeterminate outcomes were considered failures, this reduction was more marked in C/T arms. When pts with indeterminate outcomes (due to missing data or protocol deviation) were removed from analysis in the microbiologically evaluable (ME) populations, reduction in response rates were similar between treatment arms across both indications.

    Conclusion: Regardless of treatment arm or indication, lower response rates were observed in the small subset of pts with MRI vs CrCl ≥50 mL/min. The greater difference in response rates seen in C/T vs comparator arms of the MITT analyses was mainly driven by an imbalance in the number of pts with indeterminate outcomes, as this difference was not observed in protocol-adherent ME populations.

    Outcomea

    cIAI

    cUTI

    MITT

    ME

    MITT

    ME

    C/T + MTZ

    MEM

    C/T + MTZ

    MEM

    C/T

    LVX

    C/T

    LVX

    CrCL ≥50 mL/min

    N = 366

    N = 404

    N = 264

    N = 314

    N= 363

    N = 374

    N = 315

    N = 327

       Cure   n (%)

    312 (85)

    355 (88)

    251 (95)

    299 (95)

    285 (79)

    258 (69)

    266 (84)

    250 (76)

       Failure   n (%)

    29 (8)

    31 (8)

    13 (5)

    15 (5)

    54 (15)

    92 (25)

    49 (16)

    77 (24)

       Indeterminate   n(%)

    25 (7)

    18 (5)

    -

    -

    24 (7)

    24 (6)

    -

    -

    CrCL >30-<50 mL/min (MRI)

    N = 23

    N = 13

    N = 11

    N = 7

    N = 34

    N = 28

    N = 25

    N = 26

       Cure   n (%)

    11 (48)

    9 (69)

    8 (73)

    5 (71)

    21 (62)

    17 (61)

    18 (72)

    16 (62)

       Failure   n (%)

    3 (13)

    3 (23)

    3 (27)

    2 (29)

    11 (32)

    11 (39)

    7 (28)

    10 (39)

       Indeterminate  n (%)

    9 (39)

    1 (8)

    -

    -

    2 (6)

    0

    -

    -

    Magnitude of Difference in Cure (%) ≥50 vs >30-<50 mL/min

    37

    19

    22

    24

    17

    8

    12

    14

    a Clinical cure in cIAI and composite micro + clinical cure in cUTI


    Melissa Palchak, PharmD, Myra Popejoy, PharmD, Benjamin Miller, PharmD and Patricia Bernardo, ScD, Merck and Co., Inc., Kenilworth, NJ

    Disclosures:

    M. Palchak, Merck and Co., Inc: Employee , Salary

    M. Popejoy, Merck and Co., Inc.: Employee , Salary

    B. Miller, Merck and Co., Inc.: Employee , Salary

    P. Bernardo, Merck and Co., Inc.: Employee , Salary

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