Clinical trial NCT00111943: Safety and Acceptability of a Vaginal Microbicide
Official title: Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Hepatitis B, Chronic
Keywords: Anti-Infective Agents, Local
HIV Seronegativity
Tenofovir
Vaginal gel
Microbicide
Vaginal Microbicide
PMPA
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
First posted: 2005-05-27
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the safety and acceptability of a vaginal microbicide in HIV uninfected sexually active women.

Study hypothesis: The vaginal microbicide 1% tenofovir will be safe and well tolerated in HIV uninfected women who are in good general health.

Detailed description: While the male condom is effective in preventing sexual transmission of HIV, its use is hampered by deeply rooted cultural and social barriers. About half of all HIV infections worldwide occur in women, yet the only available female-controlled method of HIV prevention is the female condom. Alternative prevention tools, such as vaginal microbicides, are urgently needed to slow the rapid spread of heterosexual HIV infection.

This study will last 24 weeks, with an additional 10 weeks of follow-up for participants with chronic hepatitis B virus (HBV) infection. Participants will be randomly assigned to one of four arms. Arm A participants will insert a vaginal tenofovir 1% gel two hours prior to vaginal intercourse for a maximum of two daily applications. Arm B participants will insert a vaginal placebo gel two hours prior to vaginal intercourse for a maximum of two daily applications. Arm C participants will insert a vaginal tenofovir 1% gel once daily at bedtime or during the longest period of daily rest. Arm D participants will insert a vaginal placebo gel once daily at bedtime or during the longest period of daily rest.

A medical and menstrual history update, pregnancy test, HIV and sexually transmitted infections (STI) risk reduction counseling, and interview to assess behaviors toward vaginal gel use will occur during all study visits. HIV/STI counseling and testing, urinalysis, and blood collection will occur at study entry and at Week 24. Pelvic exam with colposcopy and vaginal swab collection will occur at study entry and Weeks 4, 12, and 24. For participants with chronic HBV, additional blood will be collected to monitor hepatitis B infection at study entry and Weeks 12, 24, 28, 32, and 36.

Eligibility criteria: Inclusion Criteria:

* HIV uninfected
* Good general health
* Sexually active
* Willing to use acceptable methods of contraception, including male latex condoms for all acts of intercourse
* Willing to undergo all study-related assessments and adhere to the requirements of the study

Exclusion Criteria:

* Menopausal or postmenopausal
* Hysterectomy
* Abnormal screening results for several gynecologic exams
* Taking or planning to take tenofovir, adefovir, or any other medication for chronic HBV infection
* History of latex allergy
* History of adverse reaction to tenofovir or adefovir
* Use of a diaphragm or spermicide for contraception
* Prior participation in the study
* Prior participation in any vaginal microbicide, spermicide, or other drug study within 30 days of study entry
* Gynecologic surgical procedure within 90 days of study entry
* Illicit injection drug use within 12 months of study entry
* History of vaginal intercourse more than an average of two times per day in the two weeks prior to study screening
* Any other criteria that, in the investigator's opinion, may interfere with the study
* Current pregnancy or previous pregnancy within 90 days of study entry
* Breastfeeding

Primary outcomes:
measure: Macroscopic evidence of damage to the cervical, vulvar, or vaginal epithelium, including ulceration and other lesions, severe erythema, or severe edema, related or not related to the study gel or applicator
Secondary outcomes:
measure: Adherence to the study gel regimen
measure: acceptability of the study gel
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Microbicide CRS
state: Alabama
city: Bronx
country: United States
facility: Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)
state: New York
city: Pune
country: India
facility: NARI Arogya Aadhar Clinic CRS
state: Maharashtra
Study officials:
affiliation: Department of Obstetrics and Gynecology and Reproductive Sciences, Magee-Women's Hospital
name: Sharon Hillier, PhD
role: STUDY_CHAIR
affiliation: Bronx-Lebanon Hospital Center
name: Jessica Justman, MD
role: STUDY_CHAIR
affiliation: National AIDS Research Institute (NARI)
name: Smita N. Joshi, MBBS
role: STUDY_CHAIR
affiliation: University of Alabama at Birmingham
name: Craig Hoesley, MD
role: STUDY_CHAIR
References:
citation: Bentley ME, Fullem AM, Tolley EE, Kelly CW, Jogelkar N, Srirak N, Mwafulirwa L, Khumalo-Sakutukwa G, Celentano DD. Acceptability of a microbicide among women and their partners in a 4-country phase I trial. Am J Public Health. 2004 Jul;94(7):1159-64. doi: 10.2105/ajph.94.7.1159.
citation: D'Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des. 2004;10(3):315-36. doi: 10.2174/1381612043386374.
citation: Mantell JE, Myer L, Carballo-Dieguez A, Stein Z, Ramjee G, Morar NS, Harrison PF. Microbicide acceptability research: current approaches and future directions. Soc Sci Med. 2005 Jan;60(2):319-30. doi: 10.1016/j.socscimed.2004.05.011.
citation: Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006 Feb 28;20(4):543-51. doi: 10.1097/01.aids.0000210608.70762.c3.
citation: Van Damme L. Clinical microbicide research: an overview. Trop Med Int Health. 2004 Dec;9(12):1290-6. doi: 10.1111/j.1365-3156.2004.01338.x.