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Efficacy and Safety of Single-Dose Oral Delafloxacin Compared With Intramuscular Ceftriaxone for Uncomplicated Gonorrhea Treatment

An Open-Label, Noninferiority, Phase 3, Multicenter, Randomized Study

Hook, Edward W. III, MD*; Golden, Matthew R., MD, MPH; Taylor, Stephanie N., MD; Henry, Eugenia, PhD§; Tseng, Carol, PhD§; Workowski, Kimberly A., MD; Swerdlow, Jerri, RN, BS; Nenninger, Ashley, PhD; Cammarata, Sue, MD

Sexually Transmitted Diseases: May 2019 - Volume 46 - Issue 5 - p 279–286
doi: 10.1097/OLQ.0000000000000971
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Background We evaluated single oral dose of delafloxacin versus single intramuscular ceftriaxone in participants with uncomplicated urogenital gonorrhea (primary objective). Secondary objectives included the efficacy, safety, and tolerability of delafloxacin versus ceftriaxone for uncomplicated urogenital, rectal, and/or pharyngeal gonorrhea.

Methods In this open-label, multicenter study, 460 participants at 25 study centers were randomized (2:1) to receive a single 900-mg oral dose of delafloxacin or 250-mg intramuscular ceftriaxone. Neisseria gonorrhoeae culture, nucleic acid amplification test, and clinical responses were evaluated. The primary efficacy end point was the urogenital microbiological cure in the urogenital microbiological intention-to-treat population; noninferiority (NI) was assessed using a 10% NI margin.

Results In the urogenital microbiological intention-to-treat population, urogenital cure rates for delafloxacin were 85.1% (194/228) versus 91.0% (91/100) for ceftriaxone (95% confidence interval, −13.18% to 1.36%). Because the lower bound of the confidence interval exceeded the prespecified −10% NI margin, delafloxacin did not demonstrate NI to ceftriaxone. Treatment failures were more often associated with N. gonorrhoeae with higher delafloxacin minimum inhibitory concentration (MIC) values. In microbiologically evaluable participants, failure occurred in 1 (0.6%) of 177 urogenital infections caused by isolates with delafloxacin MICs <0.008 μg/mL and 31 (64.6%) of 48 infections caused by isolates with delafloxacin MICs ≥0.008 μg/mL. Gastrointestinal adverse events were common with 900-mg of delafloxacin and typically included mild to moderate diarrhea, flatulence, nausea, and vomiting. The most common adverse event was diarrhea in both treatment groups.

Conclusions A single 900-mg dose of delafloxacin is not a reliable treatment of uncomplicated urogenital gonorrhea. Treatment failures were common in infections caused by N. gonorrhoeae with delafloxacin MICs ≥0.008 μg/mL. Additional testing with alternative dosing regimens could be considered.

ClinicalTrials.gov Identifier: NCT02015637.

In a phase 3 trial of participants with uncomplicated urogenital gonorrhea, single oral 900 mg delafloxacin was safe but provided insufficient therapeutic effect compared with single intramuscular 250 mg ceftriaxone.

From the *University of Alabama at Birmingham, Birmingham, AL;

University of Washington, Seattle, WA;

Louisiana State University Health Sciences Center, New Orleans, LA;

§Firma Clinical Research, Chicago, IL;

Emory University, Atlanta, GA;

Melinta Therapeutics, Lincolnshire, IL

Correspondence: Sue Cammarata, MD, Melinta Therapeutics, 300 Tri-State International Suite 272, Lincolnshire, IL 60069. E-mail: scammarata@melinta.com.

Conflicts of Interest and Sources of Funding: Each study investigator or his/her institution received funding in support of trial conduct; E.H., C.T., the study statisticians, are consultants to Melinta and receive payment for services rendered. E.W.H., M.R.G., S.N.T., E.H., and C.T. do not report an ownership interest in Melinta. J.S., A.N., and S.C. are employees of, and own stock or stock options in, Melinta. This study was funded by Melinta Therapeutics, Lincolnshire, IL.

Received for publication October 19, 2018, and accepted December 16, 2018.

© Copyright 2019 American Sexually Transmitted Diseases Association