Efficacy and Safety Study of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea

Phase 1

Conditions: ncomplicated Urogenital Gonorrhea
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2018-001780-23-DE

Lead Sponsor: GSK Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 620

Inclusion Criteria

1. The participant is =12 years at the time of signing the informed consent/assent and has a body weight >45 kg
2. The participant has clinical suspicion of a urogenital gonococcal infection (including sexual contact within the past 14 days with a partner who has confirmed gonococcal infection) with or without pharyngeal and/or rectal gonococcal infection and has 1 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 NG 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 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 NAAT assay for NG from up to 7 days before Screening (as long as the participant has not received any treatment for this infection).
3. The participant must be willing to abstain from anal, oral, and vaginal sexual intercourse or use condoms for all forms of intercourse from the Baseline Visit through the TOC Visit.
4. Male or female and must have his or her original urogenital anatomy at birth
a. Male participants: A male participant must agree to use contraception as detailed in Appendix 6 of the protocol from the Baseline Visit through completion of the TOC Visit.
b. Female participants:
A female participant is eligible to participate if she is a woman of childbearing potential(WOCBP) who is not pregnant as confirmed by a
high sensitivity urine pregnancy test at Baseline (Day 1) regardless of current or prior contraception use or abstinence, is not breastfeeding, or
is not a WOCBP.
5. The participant is capable of giving signed informed consent/assent as described in Appendix 3, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF)/assent form and in the protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1. The participant is a male with a current diagnosis of epididymitis and/or orchitis at the time of the Baseline Visit.
2. The participant is suspected or confirmed to have a CT infection and per the investigator’s judgement standard-of-care treatment for this infection cannot be safely postponed until the TOC Visit.
3. The participant has a body mass index =40 kg/m2 or has a body mass index =35.0 kg/m2 and is experiencing obesity-related health conditions such as uncontrolled high blood pressure or uncontrolled diabetes.
4. The participant has a history of sensitivity to the study treatments, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates his or her participation.
5. The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications
6. The participant has any of the following:
-Medical condition that requires medication that may be impacted by inhibition of acetylcholinesterase
OR
-Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment (e.g., ileostomy or malabsorption syndrome).
7. The participant has known anuria, oliguria, or severe impairment of renal function (creatinine clearance <30 mL/min or clinically significant elevated serum creatinine as determined by the investigator).
8. The participant, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.
9. The 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.
10. The participant has congenital long QT syndrome or known prolongation of QTc.
11. The participant has uncompensated heart failure.
12. The participant has severe left ventricular hypertrophy.
13. The participant has a family history of QT prolongation or sudden death.
14. The participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or bradyarrhythmia within the last 12 months.
15. 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 CYP3A4 inhibitor.
16. For any participant =12 to <18 years, the participant has an abnormal ECG reading.
17. The participant has a QTc >450 msec or a QTc >480 msec for participants with bundle-branch block.
18. The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.
19. The participant has a known history of cholestatic jaundice or hepatic dysfunction associated with prior use of azithromycin.
20. The participant has a known alanine aminotransferase (ALT) value >2 × upper limit of normal (ULN).
21. The participant has a known bilirubin value >1.5 × ULN (isolated bilirubin >1.5 ×ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
22. The 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 m

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with<br>uncomplicated urogenital gonorrhea caused by NG;Secondary Objective: -To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with rectal gonorrhea caused by NG <br>-To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with pharyngeal gonorrhea caused by NG <br>-To evaluate the safety and tolerability of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin;Primary end point(s): Culture-confirmed bacterial eradication of NG from the urogenital body site (i.e.,microbiological success) at the TOC(Day 4 to 8) Visit;Timepoint(s) of evaluation of this end point: at the TOC (Day 4 to 8) Visit

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Culture-confirmed bacterial eradication of NG from the rectal body site (i.e.,microbiological success) at the TOC(Day 4 to 8) Visit<br>-Culture-confirmed bacterial eradication of NG from the pharyngeal body site (i.e., microbiological success) at the TOC (Day 4 to 8) Visit<br>-Treatment-emergent AEs and serious AEs (SAEs) and change from baseline results for clinical laboratory tests and vital sign measurements;Timepoint(s) of evaluation of this end point: at the TOC(Day 4 to 8) Visit

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