2240. Efficacy, Safety and Tolerability of Gepotidacin (GSK2140944) in Patients with Acute Bacterial Skin and Soft Structure Infections from a Phase II Randomized, Adaptive Design, Dose Ranging Study
Session: Poster Abstract Session: New Antibiotics in Development
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • T-GSK0657 ID Week Clinical Studies Poster_for print_updated_FINAL.pdf (633.8 kB)
  • Background: Gepotidacin (GEP), a first in class novel triazaacenaphthylene bacterial topoisomerase inhibitors, inhibits bacterial DNA replication and has in vitro activity against key pathogens including drug-resistant strains associated with a range of conventional and biothreat infections.

    Methods: This phase 2 multicenter, randomized, adaptive design study evaluated the safety, tolerability, pharmacokinetics, and efficacy of IV/oral GEP 750 mg/1500 mg b.i.d., 1000 mg/2000 mg b.i.d. and 1000 mg/2000 mg t.i.d in subjects with suspected Gram-positive acute bacterial skin and skin structure infections (ABSSSIs) requiring hospitalization. The primary endpoint defined as an utility index was a composite of the cure rate, as measured by clinical response and outcome at the Early Efficacy Visit (48 to 72 hours after the first dose of study treatment), combined with a safety component that consisted of all drug-related AEs that led to withdrawal before completion of therapy for all subjects who received at least 1 dose of gepotidacin.  Specifically, a utility of >1.1, corresponding to early efficacy greater than 75% and withdrawal rate less than 2.5%, was defined as clinically significant.

    Results:

    Summary of Primary Endpoint (Modified ITT Population)

    GEP IV/oral

    750mg/1500mg BID

    1000mg/2000mg BID

    1000mg/2000mg TID

    Number of patients  treated

    58

    39

    25

    Clinical success (early efficacy Day 2-3, FDA endpoint)

    48 (83%)

    28 (72%)

    23 (92%)

    Clinical success (post therapy Day 12-18, EMA endpoint)

    52 (90%)

    32 (82%)

    21 (84%)

    Withdrawal due to drug related  AE

    1

    0

    0

    Any AE (mostly mild/moderate GI)

    41 (71%)

    25 (64%)

    18 (72%)

    Probability that Utility > 1.1

    0.99

    0.67

    0.99

    GEP administration as IV/oral b.i.d or t.i.d regimen for 10 days was associated with mild-to-moderate drug-related adverse events, most commonly nausea and diarrhea.  There were 2 SAEs deemed not related to study drug and 1 withdrawal related to study drug (migraine) in the 750 mg/1500 mg b.i.d. dose arm. The pharmacokinetics in adult subjects with ABSSSIs were generally comparable to healthy volunteers (Phase I data).

    Conclusion:This first report of efficacy and safety in treatment of ABSSSI supports further study of the clinical use of GEP as a first-in-class, novel mechanism of action antibacterial.

     

    William O' Riordan, MD1, Courtney Tiffany, BS2, Nicole Scangarella-Oman, MS2, Caroline Perry, PhD2, Mohammad Hossain, PhD3, Teri Ashton, PhD4 and Etienne Dumont, MD2, (1)eStudySite, San Diego, CA, (2)GlaxoSmithKline, Collegeville, PA, (3)GlaxoSmithKline, King of Prussia, PA, (4)GlaxoSmithKline, Research Triangle Park, NC

    Disclosures:

    W. O' Riordan, None

    C. Tiffany, GlaxoSmithKline: Employee , Salary and Stock

    N. Scangarella-Oman, GlaxoSmithKline: Employee and Shareholder , Salary

    C. Perry, GlaxoSmithKline: Employee and Shareholder , Salary

    M. Hossain, GlaxoSmithKline: Employee and Shareholder , Salary

    T. Ashton, GlaxoSmithKline: Employee and Shareholder , Salary

    E. Dumont, GlaxoSmithKline: Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.