Contraception and Menstrual Cycle Effect on Pharmacokinetics, Pharmacodynamics and Safety in Tenofovir Vaginal Gel Use

NCT01421368 | Completed Phase 1

• 1 other identifier: A10-114
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of the study is to examine the effects of two contraceptive methods and the menstrual cycle on the pharmacokinetics, pharmacodynamics of tenofovir 1% gel and the effect of the contraceptive methods on markers of mucosal safety.

Conditions

HIV Prevention

Outcome Measures

Primary Outcomes (1)

• Effect of oral contraceptives and DMPA on tenofovir PK, PD, and safety by comparing the following endpoints before initiation of contraceptive method and 10 weeks after initiation of contraceptive method

  * composite of pharmacokinetics for TFV in plasma, vaginal aspirate \& genital tissue * composite of pharmacokinetics for TFV-DP in PBMCs, endocervical cells \& genital tissue * rates of HIV-1 infection in an explant challenge assay (one site only) * immune cell activation \& mucosal histology in genital tissue * genitourinary AEs

  3 and 11 hours after insertion of 2 doses of study gel

Secondary Outcomes (2)

• Effect of the menstrual cycle of the tenofovir PK, PD, and safety by comparing the following endpoints 3 and 1 hours after insertion of 2 doses of study gel, in the follicular and luteal phases before initiating contraception

  3 and 11 hours after insertion of 2 doses of study gel

• To assess the effect of oral contraceptives and DMPA on markers of mucosal immunity by comparing the following endpoints (in the absence of tenofovir) before initiation of contraceptive method and 10 weeks after initiation of contraceptive method

  Before (baseline) and 10 weeks after contraceptive method start

Study Arms (2)

DMPA and tenofovir 1% gel

EXPERIMENTAL

Drug: Tenofovir 1% vaginal gel; Drug: Depo-medroxyprogesterone acetate (DMPA)

Oral contraceptive and tenofovir 1% gel

EXPERIMENTAL

Drug: Tenofovir 1% vaginal gel; Drug: Oral contraceptive: LNG 150 mcg and EE 30 mcg

Interventions

Tenofovir 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

DMPA and tenofovir 1% gel; Oral contraceptive and tenofovir 1% gel

Depo-medroxyprogesterone acetate (DMPA) DRUG

DMPA is an intramuscular injectable contraceptive containing 150 mg of medroxyprogesterone acetate. It is FDA approved for 12 weeks of use per injection.

Also known as: Depo-Provera

DMPA and tenofovir 1% gel

Oral contraceptive: LNG 150 mcg and EE 30 mcg DRUG

Each pill contains LNG 150 mcg (the active levorotatory enantiomer of norgestrel) and EE 30 mcg. Each pack contains 21 active pills and 7 placebo pills

Oral contraceptive and tenofovir 1% gel

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to use OCs or DMPA
• General good health (by volunteer history and investigator assessment) without any clinically significant systemic disease
• Currently having regular menstrual cycles of 25 to 35 days by volunteer report
• History of Pap smears and follow-up consistent with American Congress of Obstetricians and Gynecologists (ACOG) practice bulletin #99 or #109 or willing to undergo a Pap smear at Visit 1
• Willing to follow protocol requirements including abstinence, use of study condoms, and prohibited use of intravaginal products
• Willing to follow post-biopsy restrictions for at least 5 days following genital biopsies
• Meets one of the following criteria:
• Sexually abstinent and planning to remain abstinent for the duration of the study.
• In a mutually monogamous relationship for at least the last 4 months with a male partner who is at least 18 years of age, willing to use condoms, and has no known HIV infection or risks for sexually transmitted infections (STIs)
• In a mutually monogamous same-sex relationship for at least the last 4 months with a partner who is at least 18 years of age and has no known HIV infection or risks for STIs
• Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection
• Negative urine pregnancy test
• Willing to give voluntary consent, sign an informed consent form and comply with study procedures, as required by the protocol

You may not qualify if:

• History of hysterectomy
• Currently pregnant or within 2 calendar months from the last pregnancy outcome. (Note: If recently pregnant must have had at least 2 spontaneous menses since pregnancy outcome.)
• Use of any hormonal contraceptive method in the last 30 days (oral, transdermal, transvaginal, implant, or hormonal intrauterine contraceptive device)
• Injection of DMPA in the last 6 months
• Protection from pregnancy by presence of a copper IUD
• Currently breastfeeding or having breastfed an infant in the last 2 months, or planning to breastfeed during the course of the study
• History of sensitivity/allergy to any component of the study product, or topical anesthetic, or allergy to both silver nitrate and Monsel's solution
• Diagnosed with or treated for any STI or pelvic inflammatory disease in the last 6 months. (Note: Women with a history of genital herpes or condylomata who have been asymptomatic for at least 6 months may be considered for eligibility.)
• Positive test for Trichomonas vaginalis, Neisseria gonorrhoeae or Chlamydia trachomatis
• Symptomatic vulvovaginal candidiasis, Nugent score greater than or equal to 7 at screening or bacterial vaginosis (BV) at Visit 2, or urinary tract infection (UTI)
• Deep epithelial genital findings such as abrasions, ulcerations, or lacerations, or vesicles suspicious for STIs
• Positive test for HIV
• Positive test for Hepatitis B surface antigen (HBsAg)
• Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy
• Chronic or acute vulvar or vaginal symptoms (e.g., pain, irritation, or spotting)

Sponsors & Collaborators

• CONRAD: lead

Study Sites (3)

University of Pittsburgh School of Medicine, Center for Family Planning Research

Pittsburgh, Pennsylvania, 15213, United States

Location

Easter Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

Profamilia

Santo Domingo, Dominican Republic

Location

Related Publications (1)

• Zalenskaya IA, Chandra N, Yousefieh N, Fang X, Adedipe OE, Jackson SS, Anderson SM, Mauck CK, Schwartz JL, Thurman AR, Doncel GF. Use of contraceptive depot medroxyprogesterone acetate is associated with impaired cervicovaginal mucosal integrity. J Clin Invest. 2018 Oct 1;128(10):4622-4638. doi: 10.1172/JCI120583. Epub 2018 Sep 17.

  PMID: 30222141 DERIVED

MeSH Terms

Interventions

Tenofovir; Vaginal Creams, Foams, and Jellies; Medroxyprogesterone Acetate

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Feminine Hygiene Products; Equipment and Supplies; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Christine K. Mauck, M.D.

  CONRAD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2011
• First Posted: August 22, 2011
• Study Start: March 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 10, 2015

Record last verified: 2015-04

Locations

US (2); DO (1)