A Study Evaluating Efficacy and Safety of Gepotidacin Compared With Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea

Gonorrhea Clinical Trial

Official title:

A Phase III, Randomized, Multicenter, Open-Label Study in Adolescent and Adult Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04010539
• Other study ID #: 116577
• Secondary ID: 2018-001780-23
• Status: Completed
• Phase: Phase 3
• Start date: October 21, 2019
• Est. completion date: October 10, 2023

Study information

• Verified date: April 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase III, randomized, multicenter, open-label study which will be performed to evaluate efficacy and safety of oral Gepotidacin compared to intramuscular (IM) ceftriaxone plus oral azithromycin for the treatment of uncomplicated urogenital infection caused by Neisseria gonorrhoeae (N. gonorrhoeae) in adolescent and adult participants. In this study, participants will be randomly assigned to receive either oral gepotidacin or IM ceftriaxone plus oral azithromycin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 628
• Est. completion date: October 10, 2023
• Est. primary completion date: October 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Participants must be >=12 years of age at the time of signing the informed consent.

• Participants having body weight of >45 kilogram (kg).

• Participants having clinical suspicion of a urogenital gonococcal infection with or without pharyngeal and/or rectal gonococcal infection and have one of the following: male participants with purulent yellow, green, or white urethral discharge or female participants with abnormal cervical or vaginal mucopurulent discharge upon physical examination; or a prior positive culture for N. gonorrhoeae from up to 5 days before screening (as long as the participant has not received any treatment for this infection); or a Gram or equivalent stain (urogenital specimens only) positive or presumptive for Gram-negative intracellular diplococci from up to 5 days before screening (as long as the participant has not received any treatment for this infection); or a prior positive nucleic acid amplification test assay for N. gonorrhoeae from up to 7 days before screening (as long as the participant has not received any treatment for this infection).

• Participants who are willing to avoid anal, oral, and vaginal sexual intercourse or use condoms for all forms of intercourse from the Baseline Visit through the TOC Visit.

• Male or female participants having his or her original urogenital anatomy at birth.

• Male participant must agree to use contraception (male condoms) during intercourse from the Baseline Visit through completion of the TOC Visit.

• Female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance (male partners of WOCBP must use a male condom during intercourse) from the Baseline Visit through completion of the TOC Visit.

• Participants who are capable of giving signed informed consent or assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) or assent form and in study protocol.

Exclusion Criteria:

• Male participants with a current diagnosis of epididymitis and/or orchitis at the time of the Baseline Visit.

• Participant who is suspected or confirmed to have a Chlamydia trachomatis infection and per the investigator's judgement standard-of-care treatment for this infection cannot be safely postponed until the TOC Visit.

• Participant has a body mass index >=40 kilogram per square meter (kg/m^2) or has a body mass index >=35.0 kg/m^2 and is experiencing obesity-related health conditions such as high blood pressure or diabetes.

• Participant has a history of sensitivity to the study treatments, or components thereof, or a history of a drug (including erythromycin and any macrolide or ketolide drug) or other allergy that, in the opinion of the investigator or medical monitor, contraindicates his or her participation.

• Participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.

• Participants with a known cluster of differentiation 4 (CD4) count of <200 cells per cubic millimeter (cells/mm^3).

• Participant has any of the following: poorly controlled asthma or chronic obstructive pulmonary disease, acute severe pain, uncontrolled with conventional medical management, active peptic ulcer disease, Parkinson disease, Myasthenia gravis, a history of seizure disorder requiring medications for control or participant has any surgical or medical condition that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment.

• Participant has known anuria, oliguria, or severe impairment of renal function (creatinine clearance <30 milliliter per minute [mL/min] or clinically significant elevated serum creatinine as determined by the investigator).

• Participant in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.

• Participant has a serious underlying disease that could be imminently life threatening, or the participant is unlikely to survive for the duration of the study period.

• Participant has congenital long QT syndrome or known prolongation of corrected QT interval (QTc).

• Participant has uncompensated heart failure.

• Participant has severe left ventricular hypertrophy.

• Participant has a family history of QT prolongation or sudden death.

• Participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or bradyarrhythmia within the last 12 months.

• The participant is taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes (TdP) per the www.crediblemeds.org "Known Risk of TdP" category at the time of his or her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor or a strong P-glycoprotein (P-gp) inhibitor.

• For any participant >=12 to <18 years, the participant has an abnormal electrocardiogram (ECG) reading.

• The participant has a QTc >450 millisecond (msec) or a QTc >480 msec for participants with bundle-branch block.

• Participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.

• Participant has a known history of cholestatic jaundice or hepatic dysfunction associated with prior use of azithromycin.

• Participant has a known alanine aminotransferase (ALT) value >2 times upper limit of normal (ULN).

• Participant has a known bilirubin value >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Participant has a current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), including symptomatic viral hepatitis or moderate-to-severe liver insufficiency (Child Pugh class B or C).

• Participant has been previously randomized in this study or has previously been treated with Gepotidacin.

• Participant has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.

• Participant has any of the following gonococcal infections that require a different dose or duration of treatment: suspected or confirmed pelvic inflammatory disease; or suspected or confirmed gonococcal arthritis; or suspected or confirmed gonococcal conjunctivitis; or suspected or confirmed gonococcal endocarditis; or other evidence of disseminated gonococcal infection.

• Participant has received any antibacterial therapy for the treatment of a gonococcal infection within 14 days before the Baseline Visit.

• Participant has received any systemic, topical, or intravaginal antibiotics or any systemic antifungals within 7 days before the Baseline Visit.

• Participant must not use St John's wort or ergot derivatives from within 14 days before the Baseline Visit through the TOC Visit.

Related Conditions & MeSH terms

• Gonorrhea

Intervention

Drug:
• Gepotidacin
Gepotidacin will be administered as 3000 milligram (mg) oral dose (4 X 750 mg tablets) at the study site followed by 3000 mg oral dose (4 X 750 mg tablets) as an outpatient. Each dose should be taken after food consumption and with water.
• Ceftriaxone
Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site.
• Azithromycin
Azithromycin will be administered as 1000 mg oral dose (2 X 500 mg tablets) at the study site. Dose should be taken after food consumption and with water.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Carlton	Victoria
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Darlinghurst, Sydney	New South Wales
Australia	GSK Investigational Site	Prahran	Victoria
Australia	GSK Investigational Site	Southport	Queensland
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	München
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Monterrey
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Bilbao
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Sevilla
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Brighton
United Kingdom	GSK Investigational Site	Edinburgh
United Kingdom	GSK Investigational Site	Leeds
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Reading
United Kingdom	GSK Investigational Site	St Helens
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Fayetteville	North Carolina
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Longview	Texas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Mexico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Culture-Confirmed Bacterial Eradication of Neisseria Gonorrhoeae (NG) From the Urogenital Site at the Test-Of-Cure (TOC) Visit (Day 4 to 8)	Urogenital specimens were obtained for bacteriological culture at the Baseline (Day 1) and TOC (Day 4 to 8) visits and were compared to determine microbiological outcome. Microbiological success was defined as culture-confirmed elimination of baseline pathogen (NG) from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. Microbiological failure was categorized as "Bacterial Persistence (BP)" and "Unable to Determine (UTD)" outcomes. Bacterial persistence was defined as culture-confirmed persistence of baseline NG pathogen from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. UTD was defined as inability to determine the TOC NG pathogen outcome (e.g., no bacteriological sample taken for culture, sample lost, visit did not occur etc.) or the participant received other systemic antimicrobials before the TOC visit.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Number of Participants With Culture-Confirmed Bacterial Eradication of NG From the Rectal Site at the TOC Visit	Rectal specimens were obtained for bacteriological culture at the Baseline (Day 1) and TOC (Day 4 to 8) visits and were compared to determine microbiological outcome. Microbiological success was defined as culture-confirmed elimination of baseline pathogen (NG) from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. Microbiological failure was categorized as "Bacterial Persistence (BP)" and "Unable to Determine (UTD)" outcomes. Bacterial persistence was defined as culture-confirmed persistence of baseline NG pathogen from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. UTD was defined as inability to determine the TOC NG pathogen outcome (e.g., no bacteriological sample taken for culture, sample lost, visit did not occur etc.) or the participant received other systemic antimicrobials before the TOC visit.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Number of Participants With Culture-Confirmed Bacterial Eradication of NG From the Pharyngeal Site at the TOC Visit	Pharyngeal specimens were obtained for bacteriological culture at the Baseline (Day 1) and TOC (Day 4 to 8) visits and were compared to determine microbiological outcome. Microbiological success was defined as culture-confirmed elimination of baseline pathogen (NG) from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. Microbiological failure was categorized as "Bacterial Persistence (BP)" and "Unable to Determine (UTD)" outcomes. Bacterial persistence was defined as culture-confirmed persistence of baseline NG pathogen from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. UTD was defined as inability to determine the TOC NG pathogen outcome (e.g., no bacteriological sample taken for culture, sample lost, visit did not occur etc.) or the participant received other systemic antimicrobials before the TOC visit.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Any Serious Adverse Events (SAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect.	Up to 21 days
Secondary	Change From Baseline (CFB) in Hematology Parameters: Basophils, Eosinophil, Leukocytes, Neutrophils, Platelets, Lymphocytes, Monocytes, Neutrophils and Nucleated Erythrocytes	Blood samples were collected for the assessment of change from baseline in hematology parameters: basophils, eosinophil, leukocytes, neutrophils, platelets, lymphocytes, monocytes, neutrophils and nucleated erythrocytes. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb)	Blood samples were collected for the assessment of change from baseline in hematology parameters: mean corpuscular hemoglobin concentration and hemoglobin. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected for the assessment of change from baseline in hematology parameter: hematocrit. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Hematology Parameter: Erythrocytes	Blood samples were collected for the assessment of change from baseline in hematology parameter: red blood cell (RBC) count. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)	Blood samples were collected for the assessment of change from baseline in hematology parameter: mean corpuscular hemoglobin (MCH). Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)	Blood samples were collected for the assessment of change from baseline in hematology parameter: mean corpuscular volume (MCV). Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Clinical Chemistry Parameters: Urea Nitrogen (UN), Glucose, Calcium, Chloride, Sodium, Magnesium and Potassium	Blood samples were collected for the assessment of change from baseline in clinincal chemistry parameters: urea nitrogen (UN), glucose, calcium, chloride, sodium, magnesium and potassium. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine	Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters: bilirubin, direct bilirubin and creatinine levels. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein	Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters: albumin and protein. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP)	Blood samples were collected for the assessment of change from baseline in clinincal chemistry parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Number of Participants With Urinalysis Dipstick Results	Urine samples were collected for urinalysis: Glucose, Protein, Occult Blood and Ketones. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Small, Moderate, Large, Positive, 5 milligram per deciliter (mg/dL), 20 mg/dL, 30 mg/dL 50 mg/dL, 100 mg/dL, 150 mg/dL and >=500 mg/dL indicating concentrations in the urine sample. In the row title (Glucose, Baseline, Negative), Glucose indicates parameter, Baseline is the visit and Negative indicates the concentration in the urine sample. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Absolute Values in Specific Gravity of Urine	Urine samples were collected from participants to assess urine specific gravity. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Absolute Values in Potential of Hydrogen (pH) of Urine	Urine samples were collected from participants to assess urine pH. Baseline (Day 1) was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	SBP and DBP were measured in a semi-supine position after 5 minutes rest. Baseline (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Vital Sign: Pulse Rate	Pulse rate was measured in a semi-supine position after 5 minutes rest. Baseline (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)
Secondary	Change From Baseline in Vital Sign: Temperature	Temperature was measured after 5 minutes rest. Baseline (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline (Day 1) and TOC visit (Day 4 to 8)