Gent for Pharyngeal Gonorrhea (GC)

Gentamicin for Pharyngeal Gonorrhea - A Demonstration Study

The Centers for Disease Control and Prevention has identified antimicrobial-resistant (AMR) Neisseria gonorrhoeae (NG) as one of the nation's top three urgent AMR threats. Since the advent of antibiotics in the 1930s, NG has developed resistance to every first-line antibiotic. Parenteral third-generation cephalosporins are now the only class of drug with consistent efficacy against NG. New therapies are urgently needed. Although some novel antimicrobials are under development, reevaluating older drugs is another option for quickly identifying additional treatments for gonorrhea. We propose a demonstration study to test a single dose of gentamicin for the treatment of pharyngeal gonorrhea. We chose to focus on pharyngeal gonorrhea because these infections are common, play an important role in fostering gonococcal resistance, and are harder to eradicate than genital infections. Although gentamicin is 91% efficacious for genital NG, its efficacy at the pharynx may be less since streptomycin, another aminoglycoside previously used to treat gonorrhea, was not effective for pharyngeal NG. It is unknown if streptomycin's poor efficacy is indicative of limitations of aminoglycosides as a class. We plan to enroll 60 men who have sex with men in a demonstration study to be conducted at the Seattle & King County STD Clinic to test the efficacy of 360 mg of gentamicin given intramuscularly for pharyngeal gonorrhea. Secondary objectives include determining the ideal pharmacodynamic criterion (comparing in vitro minimal inhibitory concentrations (MIC) of NG to peak gentamicin serum levels), estimating resistance induction among treatment failures, and assessing the tolerability of 360 mg of IM gentamicin.

Objectives

The proposed study aims to evaluate the efficacy of a single intramuscular (IM) dose of gentamicin in the treatment of pharyngeal gonorrhea. Secondary objectives include documenting the efficacy stratified by minimal inhibitory concentration (MIC) compared with the gentamicin peak level in order to estimate a pharmacodynamic criterion. We will also attempt to determine whether gentamicin monotherapy induces antimicrobial resistance among treatment failures. Lastly, we will evaluate the tolerability of 360 mg of IM gentamicin, stratified by subject weight (i.e. weight based dosing). The specific aims are:

1. Determine the proportion of persons whose pharyngeal gonococcal infections are cured with a single dose of 360mg gentamicin intramuscularly alone.
2. Evaluate the renal safety and tolerability of 360mg IM of gentamicin.
3. Document mean peak gentamicin levels following 360mg IM of gentamicin stratified by weight.
4. Estimate the best pharmacodynamics criterion (i.e. peak/MIC ratio) for pharyngeal gonorrhea treated with gentamicin using individual and mean peak gentamicin levels and NG isolate MIC.
5. Among treatment failures, conduct exploratory analyses comparing pre- and post-treatment MIC for evidence of induced resistance.

Study Overview

• Status: Terminated
• Conditions: Pharyngeal Gonococcal Infection
• Intervention / Treatment: Drug: gentamicin 360mg IM

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Public Health -- Seattle & King County STD Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Persons diagnosed with pharyngeal gonorrhea who are not yet treated

Exclusion Criteria:

• Age less than 16 years
• Receipt of antibiotics in ≤30 days
• Known allergy to any aminoglycoside
• History of renal disease (including diagnosis of solitary kidney, chronic renal insufficiency, renal cell carcinoma etc),
• Use of concurrent nephrotoxic drugs or muscle relaxants
• History of diabetes
• History of hearing loss or tinnitus
• Concurrent infection with syphilis or chlamydia
• Pregnancy and/or nursing
• Unable to return for a follow-up visit 4-7 days (+/- 1 day).
• Study team's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Men who have sex with men (MSM) with pharyngeal gonorrhea will be treated with 360mg intramuscular gentamicin x 1.	Drug: gentamicin 360mg IM; 360mg IM of gentamicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure Rate Defined as the Percentage of Persons With Pharyngeal Gonorrhea Treated With Gentamicin 360mg IM Who Have a Negative Culture 4-7 Days Following Treatment	Negative Pharyngeal Culture	4-7 days (+/- 1 day) after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Safety	Measured by a percent change in serum creatinine from baseline to test of cure (4-7 days following treatment)	4-7 days (+/- 1 day) after treatment
Tolerability of the Injection Gentamicin 360mg IM x 1	Participant reported pain scale, with 1 being little to no pain, and 10 being the worst pain ever.	4-7 days (+/- 1 day) after treatment
Peak Gentamicin Levels	serum gentamicin concentration	at 30, 45, or 60 minutes post dose
Gentamicin Minimal Inhibitory Concentration (MIC)	laboratory defined MIC of infecting strain of N. gonorrhoeae at enrollment visit determined by agar dilution	baseline/enrollment visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Study: Look for Evidence of Induced Resistance	Among treatment failures, compare pre-treatment and post-treatment minimal inhibitory concentrations (MIC)	4-7 days (+/- 1 day) after treatment

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Lindley A Barbee, MD, MPH, University of Washington

Publications and helpful links

General Publications

• Barbee LA, Soge OO, Morgan J, Leclair A, Bass T, Werth BJ, Hughes JP, Golden MR. Gentamicin Alone Is Inadequate to Eradicate Neisseria Gonorrhoeae From the Pharynx. Clin Infect Dis. 2020 Nov 5;71(8):1877-1882. doi: 10.1093/cid/ciz1109.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): March 12, 2019
• Study Completion (Actual): March 12, 2019

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: treatment; gentamicin; gonorrhea; pharynx
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Gonorrhea; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Gentamicins
• Other Study ID Numbers: STUDY00003878; K23AI113185 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No