This study will help determine whether the agent UC-781, formulated as a gel, is safe when applied to the vagina twice daily for 14 days. It will also assess whether women find the gel acceptable to use.

Condition	Intervention	Phase
HIV	Drug: topical vaginal application of UC-781 gel	Phase I

Further Study Details: 

Primary Outcomes: Primary Endpoints:; The safety and toxicity of 0.1% UC-781 Gel and 0.25% UC-781 Gel administered intravaginally twice-daily for 14 days in sexually-active HIV-uninfected women and 0.25% UC-781 Gel administered in sexually-abstinent HIV-infected women will be assessed by:; ·Macroscopic and/or microscopic evidence of vulvar and/or vaginal epithelium damage, including ulceration, abrasion, severe erythema, and/or severe edema; ·Macroscopic and/or microscopic evidence of cervical mucosal damage including ulceration, abrasion, severe erythema, and/or severe edema; ·Symptoms of genital irritation, including burning, itching or soreness; ·Laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause
Secondary Outcomes: Secondary Endpoints:; Acceptability of 0.1% and 0.25% UC-781 Gel use by HIV-uninfected and 0.25% UC-781 Gel use by HIV-infected women will be assessed by:; ·Proportion of participants who at Day 14 visit indicate they would be ‘somewhat unlikely’ or ‘very unlikely’ to use 0.1% and 0.25% UC-781 Gel during sexual intercourse in the future compared to Control Gel users; ·Reported positive aspects of using 0.1% and 0.25% UC-781 Gel compared to Control Gel users; ·Reported negative aspects of using 0.1% and 0.25% UC-781 gel compared to Control Gel users
Expected Total Enrollment:  90

Purpose: To assess the safety and acceptability of vaginal use of 0.1% and 0.25% UC-781 gel in sexually active HIV-uninfected women, and their male partners, and sexually abstinent HIV-infected women

Design: Single-center, phase I randomized, double-blind, controlled trial with 14 days of twice-daily product or control gel exposure

Study population: Sexually active, HIV-uninfected women at low-risk for HIV and their male partners; sexually-abstinent HIV-infected women; all age 18-45

Size: 36 sexually active HIV-uninfected women and up to 36 of their male partners; 18 sexually abstinent HIV-infected women

Treatment regimen:

Stage 1: HIV-uninfected, sexually active women and 1 male partner per woman:

12 women assigned to 0.1% UC-781 twice daily x 14 days; 12 women assigned to 0.25% UC-781 twice daily x 14 days; 12 women assigned to Control Gel twice daily X 14 days.

Stage 2: HIV-infected, abstinent women: 12 assigned to 0.25% UC-781 Twice daily x 14 days; 6 assigned to Control Gel Twice daily x 14 days

Study duration: Participant accrual will take 6 months. Each participant will be followed for 14 days in Stage 1 and 21 days in Stage 2. Total study duration will be 9 months.

Study Site: The Hope Clinic of Emory University, Decatur, GA

Primary Objectives:

• To assess the safety and toxicity of 0.1%UC-781 Gel and 0.25% UC-781 Gel administered intravaginally twice-daily for 14 days on the vulvar and cervicovaginal mucosa of sexually active HIV-uninfected women
• To assess the safety and toxicity of 0.25% UC-781 Gel administered intravaginally twice-daily for 14 days on the vulvar and cervicovaginal mucosa of sexually abstinent HIV-infected women

Secondary Objectives:

• To assess the acceptability of 0.1% and 0.25% UC-781 Gel administered intravaginally twice-daily for 14 days among HIV-uninfected, and the acceptability of 0.25% Gel similarly administered to HIV-infected women
• To assess the effect of study product on vaginal microflora of HIV-uninfected and HIV-infected women
• To assess the systemic absorption of 0.1% and 0.25% UC-781 Gel when administered intravaginally
• To assess HIV viral load in genital secretions in HIV-infected women during 0.25% UC-781 Gel use
• To assess the genotypic resistance patterns of HIV in genital secretions and peripheral blood in HIV-infected women during 0.25% UC-781 Gel use
• To assess the acceptability of 0.1% and 0.25% UC-781 Gel in male sexual partners of HIV-uninfected women

Primary Endpoints:

The safety and toxicity of 0.1% UC-781 Gel and 0.25% UC-781 Gel administered intravaginally twice-daily for 14 days in sexually-active HIV-uninfected women and 0.25% UC-781 Gel administered in sexually-abstinent HIV-infected women will be assessed by:

• Macroscopic and/or microscopic evidence of vulvar and/or vaginal epithelium damage, including ulceration, abrasion, severe erythema, and/or severe edema
• Macroscopic and/or microscopic evidence of cervical mucosal damage including ulceration, abrasion, severe erythema, and/or severe edema
• Symptoms of genital irritation, including burning, itching or soreness
• Laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause

Secondary Endpoints:

Acceptability of 0.1% and 0.25% UC-781 Gel use by HIV-uninfected and 0.25% UC-781 Gel use by HIV-infected women will be assessed by:

• Proportion of participants who at Day 14 visit indicate they would be ‘somewhat unlikely’ or ‘very unlikely’ to use 0.1% and 0.25% UC-781 Gel during sexual intercourse in the future compared to Control Gel users
• Reported positive aspects of using 0.1% and 0.25% UC-781 Gel compared to Control Gel users
• Reported negative aspects of using 0.1% and 0.25% UC-781 gel compared to Control Gel users

Ages Eligible for Study:  18 Years   -   45 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

For All Females:

1. Age 18-45 years of age
2. Able to provide written informed consent
3. Normal Pap smear at screening or documentation of such within six months prior
4. Regular monthly menses or amenorrhea due to hormonal contraceptive use
5. Agree to pelvic exam, colposcopy and biopsy (if indicated) per protocol
6. Able/willing to complete Study Diary
7. Agree to abstain from sexual intercourse for 48 hours prior to the enrollment visit
8. Agree to apply assigned study gel as required per protocol

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

   • insertion of fingers/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
   • participating in other vaginal microbicide or contraceptive studies

Additional for Stage 1:

1. HIV-uninfected
2. In a monogamous sexually active relationship with one male partner throughout the study
3. Report having vaginal intercourse only with that partner at least two times per week
4. Agree to use study-provided male condoms for each act of vaginal intercourse while taking part in the study
5. Agree to inform male partner about participation

Additional Inclusion Criteria for Stage 2:

1. HIV-infected
2. Sexually abstinent or agree to abstain from sexual intercourse while taking part in the study
3. Under regular medical care for HIV management
4. CD4+ lymphocyte count > 200 /mm3 for the last 6 months
5. HIV viral load >4.0 log10 copies/ml at screening
6. Documentation of prior HIV genotype with one or more mutations conferring resistance to a NNRTI
7. Not currently on antiretrovirals
8. Willing to provide study staff with access to medical record related to their HIV infection

Inclusion Criteria for Male Partners:

1. Age 18 years or older
2. Able to give written informed consent
3. Male sexual partner of an HIV-uninfected women taking part in Stage 1 of the study

Exclusion Criteria:

Exclusion Criteria for All Females:

1. Are post-menopausal
2. Have had a hysterectomy
3. Clinically significant chronic medical condition (other than HIV) that is considered progressive.
4. History of malignancy, with the exception of basal cell or squamous cell skin cancer
5. Pregnant or planning to become pregnant in the next three months
6. Currently breastfeeding
7. History of sensitivity or allergy to latex or any compound used in this study
8. Have received antibiotics in the 14 days prior to enrollment
9. Have used a spermicide or spermicidally lubricated condom within 7 days prior to enrollment
10. Have been using a hormonal contraceptive method for less than 3 months prior to enrollment
11. Have participated in other microbicide or contraceptive studies in the past three months
12. Grade 3 or higher liver, renal or hematology abnormality, as defined by the Table for Grading the Severity of Adult Adverse Events at screening (Appendix 2)
13. Have a positive bacterial urine culture
14. Currently have a clinically detectable genital abnormality (i.e. vulvar, vaginal, cervical and/or perineal ulcer or lesions or abnormal Pap smear)

15. In the three months prior to enrollment have had any of the following:

    • An abnormal Pap smear
    • A pregnancy
    • An abortion
    • An IUD
    • Breakthrough menstrual bleeding
    • Vaginal bleeding during or following vaginal intercourse
    • Gynecologic surgery
    • Signs consistent with an STD
    • Signs of genital trauma
    • Signs of genital tract infection other than asymptomatic bacterial vaginosis (BV)

16. In the six months prior to enrollment have had any of the following:

    • History of treatment for or a diagnosis with a new STD
    • Exchanged sex for money, drugs or gifts
    • Protected (with condoms) penile-vaginal or penile-anal sexual contact with more than 4 partners
    • Unprotected (without condoms) penile-vaginal or penile-anal sexual contact with more than 1 partner
    • A male sexual partner who was diagnosed or treated for an STD (other than HIV)
    • A male sexual partner who has injected drugs
17. Are currently using, or in the last year have used intravenous drugs (except for therapeutic use), crack or other recreational drugs
18. Are currently abusing, or in the last year have abused alcohol.
19. Any other condition that in the opinion of the investigator might interfere with the evaluation of the study objectives

Additional for Stage 1:

1. Unprotected (without condoms) or protected (with condoms) penile-vaginal or penile-anal sexual contact with an HIV-infected partner in the past 6 months
2. Unwilling to use study-provided male condoms while on study Additional for Stage 2 · NNRTI mutations in plasma and/or genital secretions at screening

Please refer to this study by ClinicalTrials.gov identifier  NCT00132444

Georgia
      Hope Clinic of Emory University, Decatur,  Georgia,  30030,  United States

Study chairs or principal investigators

Frances H Priddy, MD, MPH,  Study Chair,  Emory University   

Study ID Numbers:  CDC-NCHSTP-4413
Last Updated:  August 19, 2005
Record first received:  July 11, 2005
ClinicalTrials.gov Identifier:  NCT00132444
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-23