CompletedNCT02235662Updated Jan 11, 2016

Phase I One-month Safety, PK, PD, and Acceptability Study of IVR Releasing TFV and LNG or TFV Alone

A Phase 1 interventional study of TFV IVR and TFV/LNG IVR in HIV and Contraception, sponsored by CONRAD. Completed at 2 sites in 2 countries. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-01-11.

Sponsored by CONRAD · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 86
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: Female

Study summary

The purpose of the study is to evaluate the safety of the TFV/LNG intravaginal ring (IVR), TFV-only IVR, and placebo IVR, evaluate pharmacokinetics (PK) of TFV and LNG, evaluate pharmacodynamic (PD) surrogates of contraceptive efficacy of LNG, and to evaluate acceptability of the IVRs.

Conditions studied

HIV
Contraception

Keywords

HIV
LNG
IVR
Contraception
Prevention

In context

Lead sponsor

CONRAD is the lead sponsor of 38 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: Female
Accepts healthy volunteers: Yes

Inclusion criteria

Age 18-45 years, inclusive
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)
Currently having regular menstrual cycles of 26-35 days by participant report
History of Pap smears and follow-up consistent with standard medical practice as outlined in the study manual or willing to undergo a Pap smear
Protected from pregnancy by one of the following: 1) Sterilization of either partner. Note: Women protected from pregnancy by sterilization of either partner must abstain from vaginal intercourse from 48 hours prior to Visit 3 until the sixth day after the last study visit; or 2) Willing to abstain from vaginal intercourse from Visit 1 until the sixth day after the last study visit.
Willing to abstain from any other vaginal activity and the use of vaginal product other than the study product including tampons, spermicides, lubricants, and douches starting 48 hours before Visit 3 until the sixth day after the last study visit
Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy colposcopy and genital tract sample collection
Negative urine pregnancy test
P4 ≥3 ng/ml
Willing to give voluntary consent, sign an informed consent form and comply with study procedures as required by the protocol

Exclusion criteria

Exclusion Criteria:

History of hysterectomy
Currently pregnant or within two calendar months from the last pregnancy outcome. Note: If recently pregnant must have had at least two spontaneous menses since pregnancy outcome.
Use of any hormonal contraceptive method in the last 3 months (oral, transdermal, transvaginal, implant, or hormonal intrauterine contraceptive device)
Injection of Depo-Provera in the last 10 months
Use of copper intrauterine device (IUD) after Visit 1
Currently breastfeeding or having breastfed an infant in the last two months, or planning to breastfeed during the course of the study
History of sensitivity/allergy to any component of: TFV 1% gel, topical anesthetic, or allergy to both silver nitrate and Monsel's solution.
Contraindication to LNG
In the last six months, diagnosed with or treated for any sexually transmitted infection (STI) or pelvic inflammatory disease. Note: Women with a history of genital herpes or condylomata who have been asymptomatic for at least six months may be considered for eligibility.
Nugent score greater than or equal to 7 or symptomatic bacterial vaginosis (BV) as defined by Amsel's criteria
Positive test for Trichomonas vaginalis, Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), HIV, or 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 (pain, irritation, spotting, etc.)
Known current drug or alcohol abuse which could impact study compliance
Grade 2 or higher laboratory abnormality, per the August 2009 update of the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, antivirals (e.g., acyclovir or valacyclovir) or antiretrovirals (e.g., Viread, Atripla®, Emtriva®, Complera®). Note: Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) except for treatment of dysmenorrhea during menses. Participants may use Tylenol® on an as-needed but not daily basis during the study
Participation in any other investigational trial (device, drug, or vaginal trial) within the last 30 days or planned participation in any other investigational trial during the study
History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix within the last 14 days
Abnormal finding on laboratory or physical examination or a social or medical condition which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 86 participants (actual)

Study arms

Experimental
TFV IVR
TFV IVR is an intravaginal ring 55.0 mm in diameter, consisting of single segment of polyurethane tubing with an outer diameter of 5.5 mm and filled with white TFV-containing paste. Used for one month, the IVR delivers 8-10 mg/day TFV.
Drug: TFV IVR
Experimental
TFV/LNG IVR
TFV/LNG IVR is an intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer diameter of 5.5 mm: a longer segment containing white TFV paste and a shorter one (20 mm) with a white LNG core. Used for one month, the IVR delivers 8-10 mg/day TFV and 20 μg/day LNG.
Drug: TFV IVR · Drug: TFV/LNG IVR
Placebo comparator
Placebo Intravaginal Ring
Intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer diameter of 5.5 mm containing no active experimental ingredients. Used for one month.
Other: Placebo IVR

Interventions

DrugTFV IVR
Also known as: Tenofovir Intravaginal Ring
DrugTFV/LNG IVR
Also known as: Tenofovir Levonorgestrel Intravaginal Ring
OtherPlacebo IVR
Also known as: Placebo Intravaginal Ring

What researchers measure

Primary outcomes

Number of treatment-emergent adverse events
Number of treatment-emergent adverse events
Time frame: IVR Day 1, 2, ~8, ~16-18; 24 hours and 1-2 weeks post-IVR insertion and 1-2 weeks after IVR removal
Systemic laboratory tests
Changes in Systemic laboratory tests
Time frame: Baseline and IVR Day ~16-18
Cervicovaginal ulcerations, abrasions, edema, and other findings
Development of cervicovaginal ulcerations, abrasions, edema, and other findings as assessed by naked eye and colposcopic visualization of the cervicovaginal epithelium
Time frame: Baseline, IVR Day 2, ~8 and ~16-18
Soluble markers of innate mucosal immunity and inflammatory response in cervicovaginal lavage (CVL) fluid
Changes in soluble markers of innate mucosal immunity and inflammatory response in CVL fluid
Time frame: Baseline and IVR Day ~16-18
HIV-1 target immune cell phenotype and HIV-1 activation/proliferation marker in cervicovaginal tissue (biopsy)
Changes in HIV-1 target immune cell phenotype and HIV-1 activation/proliferation marker in cervicovaginal tissue (biopsy)
Time frame: Baseline and IVR Day ~16-18
Microflora (semi-quantitative vaginal culture and/or unculturable bacteria)
Changes microflora (semi-quantitative vaginal culture and/or unculturable bacteria)
Time frame: Baseline and IVR Day ~16-18
Vaginal pH
Changes in vaginal pH
Time frame: Baseline and IVR Day ~16-18
Nugent Score
Changes in Nugent Score
Time frame: Baseline and IVR Day ~16-18

Secondary outcomes

TFV concentrations in plasma
TFV concentrations in plasma
Time frame: Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal
TFV concentrations in cervicovaginal fluid (aspirate and swab)
TFV concentrations in cervicovaginal fluid (aspirate and swab)
Time frame: 1, 2, 4 or 8 hours post-IVR insertion (randomized time point); IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal
TFV concentrations in genital tissue (biopsy)
TFV concentrations in genital tissue (biopsy)
Time frame: IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)
Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs)
TFV-DP concentrations in PBMCs
Time frame: IVR Day ~16-18
TFV-DP concentrations in genital tissue (biopsy)
TFV-DP concentrations in genital tissue (biopsy)
Time frame: IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)
LNG concentration in blood (including SHBG)
LNG concentration in blood (including SHBG)
Time frame: Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal
LNG concentration in vaginal secretions (swabs)
LNG concentration in vaginal secretions (swabs)
Time frame: Baseline; IVR Day~8
LNG concentration in cervical mucus
LNG concentration in cervical mucus
Time frame: IVR Day ~8, ~16-18; 24 hours post-IVR removal
Weight of returned IVRs
Weight of returned IVRs
Time frame: IVR Day ~16-18 (post-removal)
Amount of drug remaining in returned IVRs
Amount of drug remaining in returned IVRs
Time frame: IVR Day ~16-18 (post-removal)

Other outcomes

Cervical mucus assessment and sperm migration on the Simplified Slide test
Surrogates of contraceptive efficacy - Cervical mucus assessment
Time frame: IVR Day ~8
Ovulation by P4
Surrogates of contraceptive efficacy - Ovulation by P4
Time frame: IVR Day ~16-18
Follicular development by serum estradiol concentration
Surrogates of contraceptive efficacy - Follicular development by serum estradiol concentration
Time frame: IVR Day ~8, ~16-18
Acceptability of IVR
Acceptability of IVR as measured by a composite of the following factors: Discontinuations, Expulsions, Removals, Visible changes (such as discoloration) as documented on photographs of returned IVRs, Responses to key questions on acceptability questionnaire
Time frame: IVR Day ~16-18 (post-removal)
Pharmacodynamics
Pharmacodynamics - Anti-herpes simplex virus (HSV)-2 and Anti-HIV-1 activities in the CVL. Anti-HIV and anti-HSV activity as a percent of anti-HIV and anti-HSV activity before exposure to test product
Time frame: Baseline, IVR Day ~16-18
Pharmacodynamics
TFV anti-HIV efficacy in cervicovaginal tissues. Comparison of cervicovaginal tissue permissiveness to ex vivo infection with HIV-1 BaL between the control cycle and treatment cycle.
Time frame: Baseline, IVR Day ~16-18
Pharmacodynamic surrogates of LNG in endometrium
Findings on endometrial biopsy: Histology, Markers of endometrial function
Time frame: Baseline, IVR Day ~16-18
Endometrial thickness
Endometrial thickness as assessed by transvaginal ultrasound
Time frame: Baseline, IVR Day ~16-18
Cervicovaginal epithelial histology and epithelial integrity in cervicovaginal tissue (biopsy)
Cervicovaginal epithelial histology (thickness and number of cell layers) and epithelial integrity, as measured immuno-histochemistry (IHC) of epithelial junction proteins in cervicovaginal tissue (biopsy)
Time frame: Baseline, IVR Day ~16-18
Markers of mucosal alteration and inflammation (e.g., expression of COX-2) in cervicovaginal and endometrial tissue
Markers of mucosal alteration and inflammation (e.g., expression of COX-2) in cervicovaginal and endometrial tissue
Time frame: Baseline, IVR Day ~16-18
Microbial growth on swabs obtained from returned IVRs and microbial levels in returned IVRs
Microbial growth on swabs obtained from returned IVRs and microbial levels in returned IVRs
Time frame: IVR Day ~16-18 (post-removal)
Level of association of TFV levels between less-invasive swabs and the more invasive biopsies, and possibly between swabs and aspirates
Level of association of TFV levels between less-invasive swabs and the more invasive biopsies, and possibly between swabs and aspirates
Time frame: IVR Day 2, ~16-18; 24 hours post-IVR removal
Characterization of returned IVRs for physicochemical properties and potential chemical and/or biological measures of adherence
Characterization of returned IVRs for physicochemical properties and potential chemical and/or biological measures of adherence
Time frame: IVR Day ~16-18 (post-removal)

Study locations

2 sites

Eastern Virginia Medical School
Norfolk, Virginia 23507, United States
Profamilia
Santo Domingo, Dominican Republic

References and documents

Publications

Thurman AR, Schwartz JL, Ravel J, Gajer P, Marzinke MA, Yousefieh N, Anderson SM, Doncel GF. Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/levonorgestrel vaginal rings. PLoS One. 2019 May 20;14(5):e0217229. doi: 10.1371/journal.pone.0217229. eCollection 2019. PubMed 31107913 ↗
Thurman AR, Schwartz JL, Brache V, Clark MR, McCormick T, Chandra N, Marzinke MA, Stanczyk FZ, Dezzutti CS, Hillier SL, Herold BC, Fichorova R, Asin SN, Rollenhagen C, Weiner D, Kiser P, Doncel GF. Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLoS One. 2018 Jun 28;13(6):e0199778. doi: 10.1371/journal.pone.0199778. eCollection 2018. PubMed 29953547 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 11, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02235662
Lead sponsor: CONRAD
Responsible party: Sponsor
First posted: Sep 10, 2014
Start date: Oct 2014
Primary completion: Dec 2015
Completion: Dec 2015
Last update: Jan 11, 2016

Study contacts

Jill Schwartz, MD

study chair · CONRAD

Chris Mauck, MD

study director · CONRAD

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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