Phase I Study of Safety and Persistence of UC-781 Vaginal Microbicide - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) CONRAD
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00441909

Purpose

Vaginal microbicides are compounds that may protect women from HIV and other sexually transmitted infections (STIs). This study will determine the safety of the microbicide UC-781 by comparing the effects of keeping the microbicide in the vagina for different lengths of time.

Condition	Intervention	Phase
HIV Infections	Drug: UC-781 Drug: UC-781 placebo	Phase I

MedlinePlus related topics: AIDS

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety Study
Official Title:	Phase I Study of the Safety and Persistence of 0.1% UC-781 Vaginal Gel in HIV-1 Seronegative Women

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Local and systemic safety of a one-time dose of UC-781 0.1 % gel for vaginal use at different durations of exposure in HIV uninfected women [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Persistence of UC-781 0.1% gel following a single application [ Time Frame: At 0, 2, 4, or 8 hours post application ] [ Designated as safety issue: No ]
Systemic absorption of UC-781 following a single application of 0.1% UC-781 gel [ Time Frame: At 0, 2, 4, or 8 hours post application ] [ Designated as safety issue: No ]
In vitro anti-HIV activity of cervicovaginal lavage fluid [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Product acceptability [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Measurement of vaginal flora characteristics [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Changes in vaginal flora characteristics after a timed, single exposure [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	April 2006
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1A: Experimental Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 8 hours	Drug: UC-781 0.1% UC-781 Vaginal Gel
1B: Placebo Comparator Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 8 hours	Drug: UC-781 placebo Vaginal Gel Placebo
2A: Experimental Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 4 hours	Drug: UC-781 0.1% UC-781 Vaginal Gel
2B: Placebo Comparator Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 4 hours	Drug: UC-781 placebo Vaginal Gel Placebo
3A: Experimental Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 2 hours	Drug: UC-781 0.1% UC-781 Vaginal Gel
3B: Placebo Comparator Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 2 hours	Drug: UC-781 placebo Vaginal Gel Placebo
4A: Experimental Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 0 hours	Drug: UC-781 0.1% UC-781 Vaginal Gel
4B: Placebo Comparator Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 0 hours	Drug: UC-781 placebo Vaginal Gel Placebo

Detailed Description:

Vaginal microbicides are compounds applied to the inside of the vagina that may protect women against vaginal transmission of HIV and other STIs. This study will evaluate the safety of the vaginal microbicide UC-781. Studies have shown UC-781 to be an effective inhibitor of HIV-1 reverse transcriptase. UC-781 has been tested in animal models and in Phase I and II studies in humans. The results of these studies indicated that cervical tissue was fully protected from different variants of HIV. The purpose of this study is to assess the incidence of epithelial disruption and inflammation in the cervix, vagina, and vulva of healthy HIV uninfected women after a single exposure to UC-781 vaginal gel. This study will compare the results of leaving the microbicide in the vagina for varying lengths of time.

The duration of this study is approximately 35 days. Participants in this study will be randomly assigned to one of eight groups, and all participants will receive a single exposure of UC-781 or placebo gel. There will be five total study visits, including the screening and study entry visits. Screening will occur approximately 10 days prior to the study entry visit. At study entry, a single application of microbicide or placebo gel will be inserted for 0, 2, 4,or 8 hours in the vagina. Length of exposure time will differ, depending on which group a participant has been randomly assigned to. Following vaginal exposure to the microbicide, the microbicide will be rinsed off. Vaginal secretions will be collected to test antiviral activity against HIV and assess the amount of microbicide remaining in the vagina. Visits 3 through 5 occur at approximately 24 to 48 hours, 6 to 8 days, and 25 to 35 days following study entry.

At all visits, participants will be asked to complete a questionnaire and undergo a pelvic exam, STI tests, and vital signs measurements. Blood and urine collection will occur at each visit. On selected visits, a colposcopy will be conducted and participants will be interviewed regarding product acceptability, in addition to other measures. Between selected visits, participants will be asked to maintain sexual abstinence or use condoms.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria for Screening Visit:

HIV uninfected
General good health
Normal Pap smear within 12 months prior to screen or obtained at screening visit
Anatomy that lends itself easily to visualization of the cervix
Sexual abstinence (including vaginal, oral, and rectal) from Visit 1 to the completion of Visit 4
Agree to use condoms provided by the study between Visits 4 and 5
Agree to abstain from the use of intravaginal products or vaginal penetration throughout the study
Willing to use acceptable forms of contraception until the completion of study
Willing to participate in all study-related assessments and follow all study-related procedures

Inclusion Criteria for Study Entry:

Meet all inclusion criteria for the screening visit at Study Entry
Willing to stay in the Magee-Womens Hospital Clinical Research Center (MWH CRC) for up to 9 hours after gel insertion

Exclusion Criteria for Screening Visit:

Menopause (at least 12 months without menses in absence of long-acting progestin use)
Hysterectomy
Latex allergy
Use of a diaphragm, NuvaRing, or spermicide for contraception
Diagnosed urogenital infection or suspected infection 21 days prior to study screening. More information on this criterion can be found in the protocol.
Menses or other vaginal bleeding anticipated in the 17 days postscreening
Antibiotic or antifungal therapy (vaginal or systemic) 14 days prior to study screening
Injected nontherapeutic drugs 12 months prior to study screening
Systemic immunosuppressive drug use 60 days prior to study screening
Participation in drug, spermicide, and/or microbicide study 30 days prior to study screening
Any condition that, in the opinion of the investigator, would interfere with the study
Intravaginal use of any device or product (except tampons) 7 days prior to study screening
Surgical procedure involving the pelvis in the 90 days prior to enrollment (e.g., dilation and curettage or evacuation, cervical biopsy, cryosurgery,any other surgery involving pelvic organs or area)
Abnormal pelvic exam finding that, in the opinion of the investigator would complicate interpretation of the colposcopy
Pregnancy, or within 90 days of last pregnancy
Breastfeeding

Exclusion Criteria for Study Entry:

Meets any of the exclusion criteria of the screening visit
Diagnosed or suspected reproductive tract infection or urinary tract infection. More information on this criterion can be found in the protocol.
Menses or other vaginal bleeding anticipated in the 8 days following study entry
Injected nontherapeutic drugs between study screening and study entry
Certain abnormal laboratory values

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441909

Contacts

Contact: Ingrid Macio, PA-C

412-641-4242

imacio@mail.magee.edu

Locations

United States, Pennsylvania
Magee-Womens Hospital of University of Pittsburgh Medical Center	Recruiting
Pittsburgh, Pennsylvania, United States
Sub-Investigator: Michael Parniak, PhD
Sub-Investigator: Lisa Rohan, PhD
Sub-Investigator: Andrea Trettel, CRNP
Sub-Investigator: Abi Jett, CRNP
Sub-Investigator: Katherine Bunge, MD
Sub-Investigator: Lisa Noguchi, CNM, MSN
Sub-Investigator: Ingrid Macio, PA-C
Sub-Investigator: Thomas Cherpes, MD
Sub-Investigator: Beatrice Chen, MD
Sub-Investigator: Matthew Reeves, MD
Sub-Investigator: Mitchell Creinin, MD
Sub-Investigator: Jennifer Hayes, MD
Sub-Investigator: Heather Hohmann, MD
Principal Investigator: Sharon L. Hillier, PhD
Principal Investigator: Harold C. Wiesenfeld, MD
Sub-Investigator: Lisa Perriera, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

CONRAD

Investigators

Principal Investigator:	Sharon L. Hillier, PhD	University of Pittsburgh
Principal Investigator:	Harold C. Wiesenfeld, MD	University of Pittsburgh

More Information

Click here for more information about UC-781 This link exits the ClinicalTrials.gov site

Publications:

Davis CW, Doms RW. HIV transmission: closing all the doors. J Exp Med. 2004 Apr 19;199(8):1037-40. Epub 2004 Apr 12. Review. No abstract available.

Joshi S, Solomon S, Mayer K, Mehendale S. Preparing for efficacy trials of vaginal microbicides in Indian women. Indian J Med Res. 2005 Apr;121(4):502-9. Review.

Keller MJ, Tuyama A, Carlucci MJ, Herold BC. Topical microbicides for the prevention of genital herpes infection. J Antimicrob Chemother. 2005 Apr;55(4):420-3. Epub 2005 Mar 2. Review.

Minnis AM, Padian NS. Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions. Sex Transm Infect. 2005 Jun;81(3):193-200. Review.

Weber J, Desai K, Darbyshire J; Microbicides Development Programme. The development of vaginal microbicides for the prevention of HIV transmission. PLoS Med. 2005 May;2(5):e142. Epub 2005 May 31. Review. No abstract available.

Responsible Party:	University of Pittsburgh ( Sharon L. Hillier, PhD )
Study ID Numbers:	U19AI051661, U19 AI051661
Study First Received:	February 27, 2007
Last Updated:	September 25, 2008
ClinicalTrials.gov Identifier:	NCT00441909
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Anti-Infective Agents, Local
Healthy Women
Microbicides

UC-781
Vaginal Gel
HIV Seronegativity

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Healthy
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 14, 2009