| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Uncomplicated Urogenital Gonorrhea |
|
| E.1.1.1 | Medical condition in easily understood language |
| bacterial sexually transmitted infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with
uncomplicated urogenital gonorrhea caused by NG |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with rectal gonorrhea caused by NG
-To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with pharyngeal gonorrhea caused by NG
-To evaluate the safety and tolerability of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. |
|
| E.4 | Principal 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 moderate-to-severe liver insufficiency (Child Pugh class B or C).
23. The participant has been previously enrolled in this study or has previously been treated with gepotidacin.
24. The participant has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.
25. The participant has any of the following gonococcal infections that require a different dose or duration of treatment:
-Suspected or confirmed pelvic inflammatory disease
-Suspected or confirmed gonococcal arthritis
-Suspected or confirmed gonococcal conjunctivitis
-Suspected or confirmed gonococcal endocarditis
-Other evidence of disseminated gonococcal infection
26. The participant has received any antibacterial therapy for the treatment of a gonococcal infection within 14 days before the Baseline Visit.
27. The participant has received any systemic, topical, or intravaginal antibiotics or any systemic antifungals within 7 days before the Baseline Visit.
28. The participant must not use St John’s wort or ergot derivatives from within 14 days before the Baseline Visit through the TOC Visit. |
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| at the TOC (Day 4 to 8) Visit |
|
| E.5.2 | 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
-Culture-confirmed bacterial eradication of NG from the pharyngeal body site (i.e., microbiological success) at the TOC (Day 4 to 8) Visit
-Treatment-emergent AEs and serious AEs (SAEs) and change from baseline results for clinical laboratory tests and vital sign measurements |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| at the TOC(Day 4 to 8) Visit |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Mexico |
| United Kingdom |
| United States |
| Germany |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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