1834. Efficacy and Safety of Omadacycline in Chronic Kidney Disease (CKD) Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI): A Subgroup Analysis from the OASIS Tria
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • 87779 ProEd_ID Week OASIS Renal Poster_ 7122 03OCT2017.pdf (339.0 kB)
  • Background: Many antibiotics, including tetracycline, have adverse effects associated with renal insufficiency, necessitating dosage adjustment. Omadacycline (OMC), is a novel, broad-spectrum aminomethylcycline related to tetracyclines. In OASIS, a phase 3 ABSSSI study, intravenous (IV)-to-oral OMC was non-inferior to IV-to-oral linezolid (LZD). Here, we report the efficacy and safety of OMC vs LZD in patients with stage 1 CKD (CKD-1; GFR ≥ 90 mL/min) or stage 2/3 CKD (CKD-2/3; GFR = 30-89 mL/min) from OASIS.

    Methods: 655 patients were randomized 1:1 to OMC 100 mg IV q12h × 2 doses then 100 mg IV q24h, or to LZD per label. After ≥ 3 days’ IV therapy, patients could transition to oral OMC 300 mg q24h or oral LZD. Total treatment period was 7-14 days. Primary endpoint was early clinical response (ECR) assessed 48-72 hours after IV therapy in the modified intent-to-treat (mITT) population. Secondary endpoints were investigator-assessed clinical success at post-treatment evaluation (PTE) in the mITT and clinically evaluable (CE) populations. Safety was assessed based on adverse events (AEs), vital signs, and laboratory tests. 522 patients in the safety population had CKD-1; 119 had CKD-2/3.

    Results:

    Table 1. ECR-mITT Population

    CKD Stage

    Clinical Success, %

    Difference (95% CI)

    OMC

    LZD

    1

    87.4

    87.1

    0.3 (–5.6, 6.2)

    2/3

    82.3

    83.7

    –1.4 (–15.5, 13.6)

    Table 2. PTE Responses

    CKD Stage

    Clinical Success, %

    mITT

    CE

    OMC

    LZD

    Difference (95% CI)

    OMC

    LZD

    Difference (95% CI)

    1

    87.0

    84.8

    2.3 (–3.9, 8.4)

    96.7

    94.4

    2.3 (–1.8, 6.6)

    2/3

    90.3

    85.7

    4.6 (–7.7, 18.3)

    94.7

    91.1

    3.6 (–7.0, 16.2)

    ECR rates in OMC- and LZD-treated CKD-1 patients were slightly higher than that in CKD-2/3 patients. At PTE, clinical responses with OMC and LZD were higher than ECR in CKD-2/3. Clinical success at PTE for OMC was numerically higher than LZD for all CKD categories in both the mITT and CE populations. Cellulitis/erysipelas was more common as a baseline ABSSSI infection in patients with CKD-2/3; S.aureus was the most frequent baseline pathogen across both groups. The subgroups studied displayed a similar safety profile.

    Conclusion: In patients with CKD, IV to once-daily oral OMC was comparable to IV to twice-daily oral LZD for the treatment of ABSSSI. OMC was safe and well-tolerated with similar AEs to those without CKD.

    Thomas M. File Jr., MD, MSc, MACP, FIDSA, FCCP1, Nancy Cure-Bolt, MD2, Surya Chitra, PhD, MBA3, Evan Tzanis, BA3 and Paul McGovern, MD3, (1)Summa Health System, Akron, OH, (2)Paratek Pharmaceuticals, King of Prussia, PA, (3)Paratek Pharmaceuticals, Inc., King of Prussia, PA

    Disclosures:

    T. M. File Jr., None

    N. Cure-Bolt, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    S. Chitra, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    E. Tzanis, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    P. McGovern, Paratek Pharmaceuticals: Employee and Shareholder , Salary

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