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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Unco

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 Summary: 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.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Number of Participants With Microbiological Cure at Urethral or Cervical Sites in Each Study Arm [ Time Frame: Day 6 ]
    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.
  • Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) Considered Product-related. [ Time Frame: Day 1 through Day 31 ]
    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.


Original Primary Outcome:

  • The proportion of subjects with microbiological cure rate at urethral or cervical sites in each study arm [ Time Frame: Day 6 ]
  • The proportion of subjects reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) considered product-related. [ Time Frame: Day 1 through Day 31 ]


Current Secondary Outcome:

  • Number of Participants With Microbiological Cure at Rectal Sites in Each Study Arm [ Time Frame: Day 6 ]
    Microbiological cure was assessed at the TOC visit. Microbiological cure was derived from the Neisseria gonorrhoeae culture result and assessed by anatomical site. All participants were swabbed at the rectal site. Remel RapID NH tests were performed on pure cultures obtained from swab specimens. A subject was defined as a microbiological cure if N. gonorrhoeae was not detectable by culture at TOC.
  • Number of Participants With Microbiological Cure at Pharyngeal Sites in Each Study Arm [ Time Frame: Day 6 ]
    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. All subjects were swabbed at the pharyngeal 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.
  • Number of Participants With Clinical Cure in Each Study Arm [ Time Frame: Day 6 ]
    A clinical cure was defined as the resolution of all signs and symptoms of gonorrhea (e.g. cervical/vaginal/urethral discharge, dysuria, dyspareunia, vulvovaginal irritation, sore throat) that were present at enrollment with the exception of vaginal discharge due to yeast vaginitis or bacterial vaginosis. A clinical failure was defined by the presence of any sign or symptom of gonorrhea that was also present at enrollment with the exception of vaginal discharge due to yeast vaginitis or bacterial vaginosis. The investigator also submitted his/her determination of whether the participant met or did not meet the criteria for clinical cure (or whether it is unknown if the participant met the criteria). In the event the investigator's assessment of clinical cure did not coincide with the definitions of clinical cure/failure, the investigator's assessment was the final adjudicator.
  • Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Urethral/Cervical Specimens in Each Study Arm at Baseline. [ Time Frame: Day 1 (Baseline) ]
    Gonorrhea and Chlamydia nucleic acid amplification tests (GC/CT NAAT) were performed at baseline with specimens collected at the cervical/urethral site. Detectable nucleic acid was derived from GC/CT NAAT testing. If N. gonorrhoeae nucleic acid was detected, the result of the test was classified as positive. If no nucleic acid was detected, the result of the test was classified as negative. If a clear result could not be determined for any reason, the result of the test was classified as indeterminate.
  • Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Urethral/Cervical Specimens in Each Study Arm at Day 6. [ Time Frame: Day 6 ]
    Gonorrhea and Chlamydia nucleic acid amplification tests (GC/CT NAAT) were performed at Day 6 with specimens collected at the cervical/urethral site. Detectable nucleic acid was derived from GC/CT NAAT testing. If N. gonorrhoeae nucleic acid was detected, the result of the test was classified as positive. If no nucleic acid was detected, the result of the test was classified as negative. If a clear result could not be determined for any reason, the result of the test was classified as indeterminate.
  • Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Rectal Specimens in Each Study Arm [ Time Frame: Baseline and Day 6 ]
    Gonorrhea and Chlamydia nucleic acid amplification tests (GC/CT NAAT) were performed at baseline and Day 6 with specimens collected at the rectal site. Detectable nucleic acid was derived from GC/CT NAAT testing. If N. gonorrhoeae nucleic acid was detected, the result of the test was classified as positive. If no nucleic acid was detected, the result of the test was classified as negative. If a clear result could not be determined for any reason, the result of the test was classified as indeterminate.
  • Number of Participants With no Detectable N. Gonorrhoeae Nucleic Acid in Pharyngeal Specimens in Each Study Arm [ Time Frame: Baseline and Day 6 ]
    Gonorrhea and Chlamydia nucleic acid amplification tests (GC/CT NAAT) were performed at baseline and Day 6 with specimens collected at the pharyngeal site. Detectable nucleic acid was derived from GC/CT NAAT testing. If N. gonorrhoeae nucleic acid was detected, the result of the test was classified as positive. If no nucleic acid was detected, the result of the test was classified as negative. If a clear result could not be determined for any reason, the result of the test was classified as indeterminate.
  • 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 [ Time Frame: Day 1 (Baseline) ]
    For all positive cultures of specimens collected from the urethra or cervix, isolates were collected and tested for antimicrobial susceptibility profiles and the minimum inhibitory concentration (MIC) was determined. MIC was defined as the lowest concentrati

    Original Secondary Outcome:

    • The proportion of subjects with microbiological cure rate at rectal sites in each study arm [ Time Frame: Day 6 ]
    • The proportion of subjects with clinical cure in each study arm [ Time Frame: Day 6 ]
    • The proportion of subjects with microbiological cure at pharyngeal sites in each study arm [ Time Frame: Day 6 ]
    • The proportion of subjects with no detectable N. gonorrhoeae nucleic acid in urethral, cervical, rectum and pharynx specimen in each study arm [ Time Frame: Day 1 (Baseline) and Day 6 ]
    • The in vitro minimum inhibitory concentrations against AZD0914 and ceftriaxone of gonococcal isolates from culture [ Time Frame: Day 1 (Baseline) and Day 6 ]


    Information By: National Institute of Allergy and Infectious Diseases (NIAID)

    Dates:
    Date Received: September 19, 2014
    Date Started: November 25, 2014
    Date Completion:
    Last Updated: February 16, 2017
    Last Verified: January 5, 2016