Clinical trial NCT02257918: Randomized, Open-label Phase 2 Study of Oral AZD0914 in the Treatment of Gonorrhea
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gonorrhoea
Keywords: antibiotic
antimicrobial
AZD0914
Ceftriaxone
drug-resistant
sexually transmitted infection
urogenital gonorrhoea
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2014-10-07
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Microbiological Cure at Urethral or Cervical Sites in Each Study Arm
timeFrame: Day 6
measure: Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) Considered Product-related.
timeFrame: Day 1 through Day 31
Secondary outcomes:
measure: Number of Participants With Microbiological Cure at Rectal Sites in Each Study Arm
timeFrame: Day 6
measure: Number of Participants With Microbiological Cure at Pharyngeal Sites in Each Study Arm
timeFrame: Day 6
measure: Number of Participants With Clinical Cure in Each Study Arm
timeFrame: Day 6
measure: Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Urethral/Cervical Specimens in Each Study Arm at Baseline.
timeFrame: Day 1 (Baseline)
measure: Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Urethral/Cervical Specimens in Each Study Arm at Day 6.
timeFrame: Day 6
measure: Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Rectal Specimens in Each Study Arm
timeFrame: Baseline and Day 6
measure: Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Pharyngeal Specimens in Each Study Arm
timeFrame: Baseline and Day 6
measure: Median in Vitro Minimum Inhibitory Concentrations (MIC) Against AZD0914/ETX0914 and Ceftriaxone of Gonococcal Isolates From Culture of Isolates From the Urethral/Cervical Sites at Baseline
timeFrame: Day 1 (Baseline)
measure: Median in Vitro MIC Against AZD0914/ETX0914 and Ceftriaxone of Gonococcal Isolates From Culture of Isolates From the Urethral/Cervical Sites at Day 6
timeFrame: Day 6
measure: Median in Vitro MIC Against AZD0914/ETX0914 and Ceftriaxone of Gonococcal Isolates From Culture of Isolates From the Rectal Site at Baseline
timeFrame: Day 1 (Baseline)
measure: Median in Vitro MIC Against AZD0914/ETX0914 and Ceftriaxone of Gonococcal Isolates From Culture of Isolates From the Rectal Site at Day 6
timeFrame: Day 6
measure: Median in Vitro MIC Against AZD0914/ETX0914 and Ceftriaxone of Gonococcal Isolates From Culture of Isolates From the Pharyngeal Site at Baseline
timeFrame: Day 1 (Baseline)
measure: Median in Vitro MIC Against AZD0914/ETX0914 and Ceftriaxone of Gonococcal Isolates From Culture of Isolates From the Pharyngeal Site at Day 6
timeFrame: Day 6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Jefferson County Department of Health - STD Clinic
state: Alabama
city: Indianapolis
country: United States
facility: Indiana University - Bell Flower Clinic
state: Indiana
city: New Orleans
country: United States
facility: CrescentCare Health and Wellness Center
state: Louisiana
city: Durham
country: United States
facility: Durham County Health Department
state: North Carolina
city: Seattle
country: United States
facility: Public Health STD Clinic
state: Washington
Study officials:
References:
citation: Taylor SN, Marrazzo J, Batteiger BE, Hook EW 3rd, Sena AC, Long J, Wierzbicki MR, Kwak H, Johnson SM, Lawrence K, Mueller J. Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea. N Engl J Med. 2018 Nov 8;379(19):1835-1845. doi: 10.1056/NEJMoa1706988.