Clinical Validation of a Molecular Test for Ciprofloxacin-Susceptibility in Neisseria Gonorrhoeae

This study is a multi-center, single-arm, open-label clinical study to assess the efficacy of one dose of ciprofloxacin given orally in subjects infected with untreated gyrase A (gyrA) serine 91 genotype Neisseria gonorrhoeae (N. gonorrhoeae) as determined by a real-time Polymerase Chain Reaction (PCR) assay. The study will enroll approximately 381 subjects to obtain an eligibility target of 257 subjects, per protocol, age 18 and older regardless of gender identification who are seeking care in Sexually Transmitted Disease (STD) clinics of up to eight of the participating sites in the United States. Subjects who have untreated gyrA serine 91 genotype N. gonorrhoeae of the rectum, or male or female urogenital tract identified by a positive culture or Nucleic Acid Amplification Test (NAAT) conducted at a prior visit will be offered enrollment in the study. They will receive one dose of directly observed ciprofloxacin 500 milligrams. Subjects not consenting to participate in the study will receive treatment per local standard of care. The duration of the study for each subject will be approximately 11 through 14 days. The primary objective of this study is to determine the efficacy of ciprofloxacin for treatment of uncomplicated N. gonorrhoeae infections with gyrA serine 91 genotype.

This study is a multi-center, single-arm, open-label clinical study to assess the efficacy of one dose of ciprofloxacin given orally in subjects infected with untreated gyrase A (gyrA) serine 91 genotype Neisseria gonorrhoeae (N. gonorrhoeae) as determined by a real-time Polymerase Chain Reaction (PCR) assay. The study will enroll approximately 381 subjects to obtain an eligibility target of 257 subjects, per protocol, age 18 and older regardless of gender identification who are seeking care in Sexually Transmitted Disease (STD) clinics of up to eight of the participating sites in the United States. Subjects who have untreated gyrA serine 91 genotype N. gonorrhoeae of the rectum, or male or female urogenital tract identified by a positive culture or Nucleic Acid Amplification Test (NAAT) conducted at a prior visit will be offered enrollment in the study. They will receive one dose of directly observed ciprofloxacin 500 milligrams. Subjects not consenting to participate in the study will receive treatment per local standard of care. The duration of the study for each subject will be approximately 11 through 14 days. The primary objective of this study is to determine the efficacy of ciprofloxacin for treatment of uncomplicated N. gonorrhoeae infections with gyrA serine 91 genotype. The secondary objectives of the study are to 1) investigate the efficacy of ciprofloxacin for treatment of uncomplicated serine 91 gyrA N. gonorrhoeae infection by anatomic site and 2) to determine the sensitivity of the gyrA assay for detection of ciprofloxacin-susceptible N. gonorrhoeae infections.

Eligibility Criteria:
Inclusion Criteria:

1. Willing and able to give voluntary written informed consent before any study related procedure is performed.
2. 18 years or older, on the day of enrollment.
3. Untreated gyrA serine 91 genotype N. gonorrhoeae of the rectum, or male or female urogenital tract, as determined by the gyrA test assay on a specimen collected within 30 days of enrollment.

   \*Subjects must have gyrA serine 91 genotype detected for N. gonorrhoeae from at least one non-pharyngeal site.
4. Willing to abstain from sexual intercourse or use condoms during any sexual contact until the Test of Cure Visit (Visit 2, Day 5-10) is complete.
5. Women of childbearing potential must have no vaginal intercourse 14 days before enrollment or use an effective birth control method for 30 days before enrollment and agree to continue through visit 2.

   \*A woman is considered of childbearing potential unless post-menopausal (greater than 2 years) or surgically sterilized (tubal ligation greater than 1 year, bilateral oophorectomy, or hysterectomy).

   \*\*Acceptable birth control methods for the purposes of this study may include abstinence from intercourse with a male partner, monogamous relationship with vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, and licensed hormonal methods. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly.
6. Able to swallow pills.
7. Willing to comply with protocol requirements, including availability for follow-up for the duration of the study.
8. Agree to avoid systemic or intravaginal antibiotics with activity against N. gonorrhoeae from enrollment through Visit 2 (Day 5-10). Topical and intravaginal antifungals are permitted.
9. Agree to avoid magnesium/aluminum antacids, sucralfate, didanosine, or highly buffered drugs, up to 2 hours after receipt of study drug.

Exclusion Criteria:

1. Known renal insufficiency from clinical history.
2. Use of systemic or intravaginal antibiotics with potential activity against N. gonorrhoeae within 30 days prior to study drug administration.

   \*Topical and intravaginal antifungals are permitted.
3. Use of systemic corticosteroid drugs or other immunosuppressive therapy within 30 days prior to enrollment.
4. Receipt or planned receipt of an investigational product in a clinical trial within 30 days prior to or 7 days after treatment administration.
5. Pregnant or breastfeeding.
6. Clinical diagnosis of pelvic inflammatory disease or genital ulcer.
7. Confirmed or suspected complicated or systemic gonococcal infection, such as abdominal pain, testicular pain, epididymitis, orchitis, arthritis, or endocarditis.
8. Receipt of magnesium/aluminum antacids, sucralfate, didanosine, or highly buffered drugs, within 6 hours before receipt of study drug.
9. Mutant N. gonorrhoeae gyrA serine 91 genotype from any anatomic site, as determined by the gyrA test assay on a specimen collected within 30 days of enrollment.
10. Known allergy or history of adverse reaction to ciprofloxacin.
11. Known allergy to quinolones.
12. Previous enrollment in this study.
13. Medical condition or other factor that in the judgment of the investigator might affect ability to comply with procedures.