Tenofovir Levels Following Local Application of Tenofovir Reduced-Glycerin 1% Gel

Sponsor

CONRAD (Other)

Overall Status

Completed

CT.gov ID

NCT01768962

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compare local and systemic pharmacokinetics of tenofovir reduced-glycerin (TFV RG) 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use

Condition or Disease	Intervention/Treatment	Phase
HIV Prevention	Drug: Once Daily Application of TFV RG 1% Gel - Vaginal Drug: Once Daily Application of TFV RG 1% gel - Rectal Drug: Once Daily Application of TFV RG 1% gel - Rectal Drug: Once Daily Application of TFV RG 1% Gel - Vaginal	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Phase 1 Crossover Trial Evaluating the Pharmacokinetics of Tenofovir Reduced-Glycerin 1% Gel in the Rectal and Vaginal Compartments in Women

Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sequence A 2 weeks, 6 week washout, 2 weeks	Drug: Once Daily Application of TFV RG 1% Gel - Vaginal Vaginal application Drug: Once Daily Application of TFV RG 1% gel - Rectal Rectal application
Active Comparator: Sequence B 2 weeks, 6 week washout, 2 weeks	Drug: Once Daily Application of TFV RG 1% gel - Rectal Rectal application Drug: Once Daily Application of TFV RG 1% Gel - Vaginal Vaginal application

Arm

Intervention/Treatment

Active Comparator: Sequence A

2 weeks, 6 week washout, 2 weeks

Drug: Once Daily Application of TFV RG 1% Gel - Vaginal

Vaginal application

Drug: Once Daily Application of TFV RG 1% gel - Rectal

Rectal application

Active Comparator: Sequence B

2 weeks, 6 week washout, 2 weeks

Drug: Once Daily Application of TFV RG 1% gel - Rectal

Rectal application

Drug: Once Daily Application of TFV RG 1% Gel - Vaginal

Vaginal application

Outcome Measures

Primary Outcome Measures

Drug concentrations [10 weeks]
To compare local and systemic pharmacokinetics of tenofovir reduced-glycerin 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use

Secondary Outcome Measures

Number of adverse events Grade 2 or higher [10 weeks]
To assess the safety of tenofovir reduced-glycerin 1% gel after 2 weeks of daily rectal use and after 2 weeks of daily vaginal use

Other Outcome Measures

Inhibition of HIV by study drug in rectal and genital fluids [10 weeks]
Correlate drug levels in rectal and genital fluids with drug potency
Microflora biomarkers and gene expression from the vaginal and rectal environments [10 weeks]
Determine changes in microflora biomarkers and gene expression from the vaginal and rectal environments after 2 weeks of daily rectal versus 2 weeks of daily vaginal use of tenofovir reduced-glycerin 1% gel at sites with capacity

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 21 through 45 years (inclusive) at Screening
Able and willing to provide written informed consent
Able and willing to comply with all study procedure requirements, including, clinical and laboratory assessments, vaginal and rectal examinations, urine and blood testing, as well as attendance at all scheduled study visits
In general good health at Screening and Enrollment as determined by the Investigator of Record (IoR)/ or designee
Negative pregnancy test at Screening and Enrollment
HIV-negative at Screening and Enrollment
Able and willing to provide adequate locator information
Willingness to use study-provided male condoms for the duration of study participation for penetrative intercourse
Per participant report at Screening, regular menstrual cycles with at least 21 days between menses (does not apply to participants who report using a progestin-only method of contraception at screening, e.g., Depo-Provera, progesterone-containing IUDs or extended use of oral contraceptives)
Per participant report at Enrollment, using an effective method of contraception and intending to use an effective method for the duration of study participation; effective methods include:

Hormonal methods, excluding vaginal rings
Intrauterine device (IUD) inserted at least 42 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions)
Sterilization of participant or partner at least 42 days prior to Enrollment
Self-identifies as a woman who has sex with women exclusively
Sexually abstinent for the at least 90 days prior to enrollment and the intention to remain sexually abstinent for the duration of study participation

Per participant report at Screening, states a willingness to refrain from inserting any non-study vaginal or rectal products or objects into the vagina or rectum, including but not limited to, spermicides, female condoms, diaphragms, contraceptive vaginal rings, vaginal medications, menstrual cups, cervical caps (or any other vaginal barrier method), vaginal/rectal douches, enemas, non-study approved lubricants, sex toys (vibrators, dildos, etc.), and tampons for the duration of the study product use periods and for 24 hours prior to each scheduled study clinic visit.
Pap result consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) or satisfactory evaluation of non-Grade 0 Pap result with no treatment required per clinical judgment of IoR or designee in the 12 calendar months prior to the Enrollment Visit
At Screening, participant agrees not to take part in other research studies involving drugs, medical devices, or vaginal/rectal products for the duration of study participation (including the time between the Screening and Enrollment visits)

Participants in the biopsy subset must also meet the following criteria at Screening to be eligible for inclusion:

Willing to abstain from inserting anything into the vagina or rectum for 72 hours prior to and following the collection of these samples, including vaginal and rectal intercourse
Willing to restrict the use of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and/or other drugs that are associated with the increased likelihood of bleeding following mucosal biopsy collection for 72 hours prior to and following the collection biopsies

Exclusion Criteria:

Participant report of any of the following:
Known adverse reaction to the study product (ever)
Known adverse reaction to latex (ever)
Current male sex partner with known history of adverse reaction to latex (ever)
History of serum HBsAg positivity (ever)
Non-therapeutic injection drug use in the 12 calendar months prior to Enrollment
Sexually transmitted infections (STI) or reproductive tract infection (RTI) requiring treatment in the 6 calendar months prior to Enrollment
Post-exposure prophylaxis (PEP) for possible HIV-1 infection within the 6 calendar months prior to Enrollment
Last pregnancy outcome within 90 days or less prior to Enrollment
Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage) within the 42 days prior to Enrollment Note: This does not include biopsy for the evaluation of an abnormal pap result or endometrial biopsy that occurred more than 7 days prior to Enrollment, provided that all other inclusion/exclusion criteria are met.
Participation in any other research study involving drugs, medical devices or vaginal products 42 days or less prior to Enrollment
Anticipated IUD replacement within the next 3 months or an IUD inserted 42 days or less prior to Enrollment
Participant report at Screening and/or Enrollment intention of becoming pregnant in the next 3 months
Currently breastfeeding at the time of Screening and/or Enrollment
History of bleeding problems (Participants in the biopsy subset only)
Laboratory abnormalities at Screening greater than or equal to a Grade 2*:
Aspartate aminotransferase (AST) or alanine transaminase (ALT)
Hemoglobin
Platelet count
Serum creatinine Otherwise eligible participants with an exclusionary test result(s) listed above may be re-tested during the screening process. If a participant is re-tested and a non-exclusionary result is documented within the 42 days of providing informed consent, the participant may be enrolled.
Urinary tract infection (UTI) at Screening and/or Enrollment Note: Otherwise eligible participants diagnosed with UTI during Screening will be offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 42 days of obtaining informed consent, the participant may be enrolled.
Pelvic inflammatory disease or an STI or RTI requiring treatment per current World Health Organization (WHO) guidelines at Screening and/or Enrollment
Clinically apparent Grade 2 or higher pelvic** and/or rectal*** examination finding (observed by study staff) at Screening and/or Enrollment Note: Cervical bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the IoR/designee is considered expected non-menstrual bleeding and is not exclusionary.

Note: Otherwise eligible participants with exclusionary pelvic and/or rectal examination findings may be enrolled/randomized after the findings have improved to a non-exclusionary severity grading or resolved. If improvement to a non-exclusionary grade or resolution is documented within 42 days of providing informed consent, the participant may be enrolled.

Any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009) ** per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009), Addendum 1 Female Genital Grading Table for Use in Microbicide Studies *** per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009), Addendum 3 Rectal Grading Table for Use in Microbicide Studies (Clarification dated May 2012).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Infectious Disease Epidemiologic Research, Mailman School of Public Health, Columbia University	New York	New York	United States	10032

Sponsors and Collaborators

CONRAD
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)

Investigators

Study Chair: Gonasagrie Nair, MBChB, Centre for the AIDS Programme of Research in South Africa (CAPRISA) - eThekwini CRS
Principal Investigator: Jessica Justman, MD, Columbia University