Safety Study of UC-781 Vaginal Microbicide

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Phase I Study of the Safety and Acceptability of UC-781 Topical Vaginal Microbicide in Women and Acceptability in Their Male Partners,Chiang Rai, Thailand

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Placebo gel
* Drug: UC 781


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>UC 781 0.1% carbomer gel | Drug: UC 781<br>* UC 781 0.1% or UC 781 0.25%, applied vaginally twice daily for two intermenstrual weeks<br>|
| Experimental: 2<br>UC 781 0.25% carbomer gel | Drug: UC 781<br>* UC 781 0.1% or UC 781 0.25%, applied vaginally twice daily for two intermenstrual weeks<br>|
| Placebo Comparator: 3<br>Placebo vaginal gel | Drug: Placebo gel<br>* HEC (hydroxyethyl cellulose) Control Gel applied vaginally twice daily for two weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genital tract inflammation or epithelial disruption as assessed by naked eye and colposcopic inspection according to established guidelines |  | 2 weeks | 
| Symptoms of irritation |  | two weeks | 
| Changes in vaginal flora |  | Two weeks | 
| Assessment of pro-inflammatory cytokines in the genital tract |  | Two weeks | 
| Other product-related adverse events |  | Two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acceptability of UC-781 gel use |  | Two weeks | 
| systemic absorption of UC-781 |  | Two weeks | 
| anti-HIV activity of genital secretions in the presence of UC-781 gel |  | Two weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Microbicides, HIV seronegativity