Safety and Acceptability of Tenofovir 1% Gel in Adolescent Females

NCT02245945 | Withdrawn Phase 1

• 1 other identifier: A14-130
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this trial is to assess the safety and acceptability of Tenofovir (TFV) 1% gel in adolescent females over 12 weeks of a minimum of twice weekly dosing following the BAT24 regimen.

Conditions

HIV Prevention

Keywords

HIV; prevention

Outcome Measures

Primary Outcomes (3)

• Changes in genitourinary adverse events (AEs)

  Number of genitourinary adverse events (AEs)

  24 hours after single dose; 1, 2, 4, 8 and 12 weeks during/after repeat dosing

• Changes in soluble markers of inflammation in cervicovaginal fluid (CVF)

  changes in soluble markers of inflammation in cervicovaginal fluid (CVF)

  Baseline; 24 hours after single dose; 12 weeks after repeat dosing

• Changes in vaginal microflora as assessed by Gram stain and semi-quantitative vaginal culture

  Changes in vaginal microflora as assessed by Gram stain and semi-quantitative vaginal culture

  Baseline and 12 weeks after repeat dosing

Secondary Outcomes (6)

• Responses to key questions on acceptability questionnaire

  2, 8 and 12 weeks during/after repeat dosing

• TFV concentration in plasma

  2 and 24 hours after single dose

• TFV concentration in CVF

  24 hours after single does; 2, 4, 8, and 12 weeks during/after repeat dosing

• Anti-HIV and anti-herpes simplex virus (HSV)-2 activity in the CVF

  Baseline; 24 hours after single-dose; 12 weeks after repeat dosing

• Real time adherence via internet-based diary

  12 weeks

Study Arms (2)

TFV 1% gel

EXPERIMENTAL

Participants will be instructed to use TFV 1% vaginal gel according to the BAT 24 regimen (2 gel doses) at least twice per week, regardless of sexual frequency. The BAT24 dosing regimen when used with sex is defined as one dose of gel within 12 hours before sex and a second dose of gel as soon as possible within 12 hours after sex and no more than two doses in a 24 hour period. Participants who do engage in sexual intercourse should use the BAT24 regimen with each sex act. If used without sex, the BAT24 dosing regimen is defined as 2 doses of gel administered 2-24 hours apart, with no more than two doses in a 24 hour period.

Drug: TFV 1% vaginal gel

hydroxyethylcellulose (HEC) placebo gel

PLACEBO COMPARATOR

Participants will be instructed to use HEC placebo gel according to the BAT 24 regimen (2 gel doses) at least twice per week, regardless of sexual frequency. The BAT24 dosing regimen when used with sex is defined as one dose of gel within 12 hours before sex and a second dose of gel as soon as possible within 12 hours after sex and no more than two doses in a 24 hour period. Participants who do engage in sexual intercourse should use the BAT24 regimen with each sex act. If used without sex, the BAT24 dosing regimen is defined as 2 doses of gel administered 2-24 hours apart, with no more than two doses in a 24 hour period.

Drug: HEC Placebo Gel

Interventions

TFV 1% vaginal gel DRUG

Tenofovir 1% gel is supplied as a clear, transparent, viscous gel packaged in pre-filled single use applicators. Each applicator contains 4.0 mL of tenofovir gel (equal to 4.4 gm) at a concentration of 1% (weight for weight) formulated in purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben and hydroxyethylcellulose, and is pH adjusted to 4-5.

TFV 1% gel

HEC Placebo Gel DRUG

Placebo gel contains hydroxyethylcellulose (HEC) as the gel thickener, purified water, sodium chloride, sorbic acid and sodium hydroxide. The gel is isotonic and formulated at a pH of 4.4. Each pre-filled applicator will contain approximately 4 mL of placebo gel for delivery.

hydroxyethylcellulose (HEC) placebo gel

Eligibility Criteria

• Age: 15 Years - 17 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age 15 through 17 years, inclusive, as per site policy
• General good health (by volunteer history and per investigator discretion) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes)
• Able to communicate in spoken and written English
• Willing to following instructions regarding vaginal activity and vaginal products as follows:
• Willing to abstain from all vaginal activity, including intercourse, for 48 hours prior to Visit 2 and 48 hours prior to Visit 7
• Willing to abstain from the use of vaginal products other than the study product including spermicides, lubricants, and douches for the duration of study participation.
• Note: Tampons may be used for menses, but pads should be used for any other intermenstrual spotting or bleeding.
• Assessment of onset and progression of puberty as measured by Tanner Stage 4 or 5
• History of consensual penile-vaginal intercourse (at least one episode in participant's lifetime)
• Negative urine pregnancy test
• Use of an effective method of contraception for at least the past 30 days (per participant report) and intended use for the duration of study participation. Effective methods include:
• Hormonal methods (excluding contraceptive ring)
• Intrauterine contraception (IUC)
• Note: An IUC must be in place for at least 15 days prior to enrollment
• Willing to give voluntary assent, and comply with study procedures as required by the protocol assent and willing for parent/guardian to provide written informed consent for participation as per Institutional Review Board (IRB) requirements. Emancipated minors may give their own informed consent.

You may not qualify if:

• Known adverse reaction to study products (ever) or latex, per participant report
• Non-therapeutic injection drug use in the last 12 calendar months
• Post-exposure prophylaxis (PEP) for HIV-1 exposure within the last 6 calendar months
• Currently pregnant or within 30 days from the last pregnancy outcome.
• Note: If recently pregnant must have had at least two spontaneous menses since pregnancy outcome.
• History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix within the last 14 days
• Intention to become pregnant in the next 6 months
• Currently breastfeeding or having breastfed an infant in the last two months, or planning to breastfeed during the course of the study
• Positive for HIV
• Grade 2 or higher as per the Division of AIDS (DAIDS) Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) of the following:
• Alanine transaminase (ALT), aspartate aminotransferase (AST)
• Creatinine
• Hemoglobin
• Platelet count
• Hepatitis B surface antigen (HBsAg)

Sponsors & Collaborators

• CONRAD: lead

Study Sites (2)

Albert Einstein College of Medicine

The Bronx, New York, 10451, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

Vaginal Creams, Foams, and Jellies

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Feminine Hygiene Products; Equipment and Supplies

Study Officials

• Jill Schwartz, MD

  CONRAD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 22, 2014
• Primary Completion: April 1, 2015
• Last Updated: May 1, 2015

Record last verified: 2015-04

Locations

US (2)