Randomized, Open-label Phase 2 Study of Oral AZD0914 in the Treatment of Gonorrhea

A Randomized, Open-label Phase 2 Study to Evaluate the Efficacy and Safety of a Single Dose of Oral AZD0914 Compared to Intramuscular Ceftriaxone in the Treatment of Male and Female Subjects With Uncomplicated Gonorrhea

This is a multi-center Phase 2 randomized, open-label study in approximately 180 adult male and female subjects, between the ages of 18 and 55, who are in good health and meet all eligibility criteria. The study is designed to assess the safety and efficacy of an antimicrobial investigational product, AZD0914 manufactured by AstraZeneca, administered to adults to treat uncomplicated urogenital gonorrhea compared to treatment with ceftriaxone. Subjects will be randomly assigned 70:70:40 to receive a single, oral dose of 2000 mg of AZD0914, 3000 mg of AZD0914, or intramuscular dose of 500 mg of ceftriaxone. The drug name is also known as ETX0914.

Uncomplicated gonorrhea is currently the second most common bacterial sexually transmitted infection (STI) worldwide and, accordingly, is a serious public health problem. This is a multi-center Phase 2 randomized, open-label study in approximately 180 adult male and female subjects, between the ages of 18 and 55, with uncomplicated cervical or urethral gonorrhea. The study is designed to assess the safety and efficacy of an antimicrobial investigational product, AZD0914 manufactured by AstraZeneca, administered to adults to treat uncomplicated urogenital gonorrhea compared to treatment with intramuscular ceftriaxone. Subjects will be randomly assigned 70:70:40 to receive a single, oral dose of 2000 mg of AZD0914, 3000 mg of AZD0914, or intramuscular dose of 500 mg of ceftriaxone. The study duration is 11 months and subject participation of 30 days. Subjects with 1) untreated urethral or cervical gonorrhea identified via laboratory testing at a prior visit, or 2) untreated subjects acknowledging anal, oral, or vaginal sexual contact in the past 14 days with someone diagnosed with gonorrhea, or 3) signs and symptoms of urethral or cervical gonorrhea will be offered enrollment in the study and consented. The primary objective assess the efficacy by microbiological cure rate of 2000 mg or 3000 mg AZD0914 compared to 500 mg ceftriaxone for the treatment of uncomplicated urogenital gonorrhea. The second primary objective assess the safety and tolerability of a single oral dose of 200 mg or 3000 mg AZD0914 compared to 500 mg ceftriaxone in adult subjects with uncomplicated urogenital gonorrhea. The drug name is also known as ETX0914.

Inclusion Criteria:

1. Untreated subjects with signs and symptoms of urethral or cervical gonorrhea, or confirmed urethral or cervical gonorrhea* or any type of sexual contact in the past 14 days with an infected individual. *As defined by positive culture, NAAT test, or Gram-stain 2. Subject is able to give voluntary written informed consent before any study related procedure is performed 3. Willingness to comply with all protocol requirements 4. Male or non-pregnant female 18 to 55 years of age, inclusive 5. If the subject is female, a negative urine pregnancy test at Visit 1 prior to receiving study drug 6. Subject willing to abstain from anal, oral, and vaginal sexual intercourse or use condoms for 7 days following study drug dosing to prevent potential gonococcal reinfection 7. Male subjects must be surgically sterilized or use condoms for 7 days following study drug dosing 8. Female subject must be of non-childbearing potential* or if of childbearing potential, she must be using a highly effective method of birth control** *Non-childbearing potential is defined as being post-menopausal for at least two years, status after bilateral oophorectomy or status after hysterectomy. **Female subjects must avoid becoming pregnant by using one of the following acceptable methods of birth control for 30 days prior to study drug dosing: --Intrauterine contraceptive device; OR --Oral contraceptives; OR --Implanon®,Nexplanon®, DepoProvera®, contraceptive skin patch or NuvaRing®, OR --Tubal ligation OR --Abstinence AND --for 30 days following dosing, any method above should be used plus the required use of a barrier method (condom) by the male partner (even if vasectomized)

Exclusion Criteria:

1. Confirmed or suspected, complicated or systemic gonorrhea such as pelvic inflammatory disease, testicular pain, epididymitis, arthritis, conjunctivitis or endocarditis or clinical proctitis. 2. Known concomitant infection which would require immediate additional systemic antibiotics 3. Female subject currently breastfeeding 4. Use of any systemic or intravaginal antibiotics with activity against N. gonorrhoeae or systemic antivirals within 30 days prior to study drug administration (topical and intravaginal antifugals are permitted). 5. Use of systemic corticosteroid drugs or other immunosuppressive therapy within 30 days prior to enrollment 6. Cytotoxic chemotherapy or radiation therapy within the previous 3 months 7. Known chronic renal, hepatic (including chronic hepatitis B or hepatitis C infection) or hematologic impairment, or other condition that could interfere with the absorption or metabolism of study drug 8. Any concomitant condition that, in the opinion of the Investigator, would preclude an evaluation of a response or make it unlikely that the course of therapy and follow-up could be completed 9. Subject HIV-infected and taking antiretroviral medication -- Subject not HIV-infected and taking antiretroviral for pre- or post- exposure prophylaxis -- Subject newly diagnosed with HIV infection or known to be HIV infected with evidence of immunosuppression, such as documented or patient reported CD4 count of < 200 10. Known allergy to cephalosporin or penicillin antibiotics 11. Receipt or planned receipt of an investigational product in a clinical trial within 30 days prior to or 7 days after study dose administration 12. Female subject is not willing to defer treatment for bacterial vaginosis until Visit 2 if she tests positive for bacterial vaginosis at Visit 1. 13. Use of drugs that act as inducer/inhibitors of CYP3A4/5 or the P-gp efflux transporter* within 30 days prior to study drug administration *such as itraconozale, fluconazole, ketoconazole, verapamil, diltiazem, amiodarone, felodipine, carbamazepine, phenytoin, or St. John's wort 14. Subjects known to be co-infected with chlamydia prior to study entry 15. Subjects with medically documented cardiac arrhythmia 16. Known allergy to lidocaine (or local anesthetics of the amide type, e.g., articaine, bupivacaine, mepivacaine, prilocaine, ropivacaine) or the antimicrobial preservative methylparaben.