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

NCT02257918 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 14-0014HHSN272201300012I
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 5

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.

Conditions

Gonorrhoea

Keywords

antibiotic; antimicrobial; AZD0914; Ceftriaxone; drug-resistant; sexually transmitted infection; urogenital gonorrhoea

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Microbiological Cure at Urethral or Cervical Sites in Each Study Arm

  Microbiological cure was assessed at the Test of Cure visit (TOC). Microbiological Cure was derived from the Neisseria gonorrhoeae culture result and assessed by anatomical site. Male participants were swabbed at the urethral site and female participants at the cervical site. Remel RapID NH tests were performed on pure cultures obtained from swab specimens. A participant was defined as a microbiological cure if N. gonorrhoeae was not detectable by culture at TOC.

  Day 6

• Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) Considered Product-related.

  Adverse events are defined as any untoward medical occurrence regardless of its causal relationship to the study treatment. Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation thereof was a congenital anomaly/birth defect; or may have jeopardized the subject or required intervention to prevent one of the outcomes. Relationship to study product was determined by the investigator and defined as a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event.

  Day 1 through Day 31

Secondary Outcomes (13)

• Number of Participants With Microbiological Cure at Rectal Sites in Each Study Arm

  Day 6

• Number of Participants With Microbiological Cure at Pharyngeal Sites in Each Study Arm

  Day 6

• Number of Participants With Clinical Cure in Each Study Arm

  Day 6

• Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Urethral/Cervical Specimens in Each Study Arm at Baseline.

  Day 1 (Baseline)

• Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Urethral/Cervical Specimens in Each Study Arm at Day 6.

  Day 6

Study Arms (3)

Group 1

EXPERIMENTAL

N = 70 subjects receive single oral dose , 2000 mg of AZD0914

Drug: AZD0914

Group 2

EXPERIMENTAL

N =70 subjects receive single oral dose , 3000 mg of AZD0914

Drug: AZD0914

Group 3

ACTIVE COMPARATOR

N = 40 subjects receive single intramuscular dose, 500 mg of ceftriaxone

Drug: Ceftriaxone

Interventions

AZD0914 DRUG

AZD0914 is an antimicrobial amorphous nonsterile powder. Group 1 receive 2000 mg; Group 2 receive 3000 mg. The drug name is also known as ETX0914.

Group 1; Group 2

Ceftriaxone DRUG

Ceftriaxone is a broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears. A white to yellowish orange crystalline powder. Group 3 receives 500 mg reconstituted with 1 ml Lidocaine HCL 1%, intramuscularly.

Group 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. 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)

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

Jefferson County Department of Health - STD Clinic

Birmingham, Alabama, 35233-1502, United States

Location

Indiana University - Bell Flower Clinic

Indianapolis, Indiana, 46202-5112, United States

Location

CrescentCare Health and Wellness Center

New Orleans, Louisiana, 70119, United States

Location

Durham County Health Department

Durham, North Carolina, 27701-3720, United States

Location

Public Health STD Clinic

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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.

  PMID: 30403954 DERIVED

MeSH Terms

Conditions

Gonorrhea; Sexually Transmitted Diseases

Interventions

zoliflodacin; Ceftriaxone

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Communicable Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Stephanie N. Taylor, MD
• Organization: Louisiana State University Health Sciences Center

staylo2@lsuhsc.edu

(504) 658-2622

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2014
• First Posted: October 7, 2014
• Study Start: November 25, 2014
• Primary Completion: December 30, 2015
• Study Completion: December 30, 2015
• Last Updated: March 22, 2017
• Results First Posted: February 8, 2017

Record last verified: 2016-01-05

Locations

US (5)