Safety Study of UC-781 Vaginal Microbicide

• Genital tract inflammation or epithelial disruption as assessed by naked eye and colposcopic inspection according to established guidelines [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
• Symptoms of irritation [ Time Frame: two weeks ] [ Designated as safety issue: Yes ]
• Changes in vaginal flora [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]
• Assessment of pro-inflammatory cytokines in the genital tract [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]
• Other product-related adverse events [ Time Frame: Two weeks ] [ Designated as safety issue: Yes ]

• Genital tract inflammation or epithelial disruption as assessed by naked eye and colposcopic inspection according to established guidelines
• Symptoms of irritation
• Changes in vaginal flora
• Assessment of pro-inflammatory cytokines in the genital tract
• Other product-related adverse events

• acceptability of UC-781 gel use [ Time Frame: Two weeks ] [ Designated as safety issue: No ]
• systemic absorption of UC-781 [ Time Frame: Two weeks ] [ Designated as safety issue: No ]
• anti-HIV activity of genital secretions in the presence of UC-781 gel [ Time Frame: Two weeks ] [ Designated as safety issue: No ]

• acceptability of UC-781 gel use
• systemic absorption of UC-781
• anti-HIV activity of genital secretions in the presence of UC-781 gel

This study will help determine whether UC-781 gel is safe when applied to the vagina twice daily for 14 days, and will assess whether women and men find the gel acceptable to use.

• Drug: Placebo gel
  HEC (hydroxyethyl cellulose) Control Gel applied vaginally twice daily for two weeks
• Drug: UC 781
  UC 781 0.1% or UC 781 0.25%, applied vaginally twice daily for two intermenstrual weeks

• Experimental: 1
  UC 781 0.1% carbomer gel
  Intervention: Drug: UC 781
• Experimental: 2
  UC 781 0.25% carbomer gel
  Intervention: Drug: UC 781
• Placebo Comparator: 3
  Placebo vaginal gel
  Intervention: Drug: Placebo gel

Inclusion Criteria for women:

• Age 18-50 years old
• Regular menses
• HIV-1 seronegative at screening
• Normal Pap smear at screening or documented normal Pap smear within six months prior to screening
• No evidence of reproductive tract infection (RTI)
• Willing and able to comply with study procedures, including pelvic exams, colposcopy, maintaining a study coital and symptom log, and applying assigned study gel per protocol
• Agree to abstain from sexual intercourse for 24 hours prior to the enrollment visit

• Agree to abstain from the following activities from at least 48 hours prior to enrollment through the Day 14 visit:

  • Insertion of fingers and other objects into the vagina
  • Receiving oral sex
  • Receiving anal sex
  • Using a diaphragm, cervical cap, female condom, or vaginal contraceptive ring
  • Using vaginal products other than the study gels, including douches, lubricants, or feminine hygiene products
• In a monogamous sexually active relationship with one male partner
• Report having vaginal intercourse only with that partner at least two times per week
• No other reported partner in the prior six months and no plan to have another partner for the duration of the study
• Agree to use condoms for each act of vaginal intercourse during participation in the study
• Their male partner is informed and also consents to participate in the study
• Willing to have male partner informed and treated if an STD is diagnosed at screening or during the study

Inclusion Criteria for men:

• Age 18 years or older
• HIV-seronegative and free of other STI at screening exam
• One female sexual partner; no other reported partner in the prior six months and no plan to have another partner for the duration of the study
• Willing and able to comply with study procedures, including clinic visits, interviews and acceptability evaluation, and consistent use of condoms during enrollment in the study
• Willing to have female partner informed and treated if an STD is diagnosed at screening or during the study

Exclusion Criteria for women:

• Pregnancy or desire to become pregnant at time of study participation
• Currently breastfeeding
• Delivery or abortion within last eight weeks

• History of any male sexual partner other than current partner in past six months

  - No abnormal (DAIDS grade 1 or higher) laboratory results at baseline, including hematology, liver and kidney function

• History of post-coital vaginal bleeding in the past three months
• History of surgery to remove uterus or cervix
• History of surgery on the external genitalia, vaginal, or cervix in the past month
• Clinically significant chronic medical condition that is considered progressive, including cardiopulmonary disease, renal disease, hepatic disease, diabetes mellitus.
• History of sensitivity/allergy to latex
• Existence of a clinically detectable genital abnormality at screening (e.g. ulcer, congenital abnormality, any lesion with mucosal disruption)
• Concurrent participation in another trial of a vaginal product
• Have any other condition that in the opinion of the investigator might interfere with the evaluation of the study objectives

Exclusion Criteria for men:

• History of genital surgery in the past month
• Clinical or laboratory evidence of an STI.
• History of sensitivity/allergy to latex
• History of any sexual partner other than their current partner in the past six months

• Ministry of Health, Thailand
• CONRAD