AzTrials
AzTrials

HIVPhase 1NCT02235662

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

A Phase 1 study testing TFV IVR and TFV/LNG IVR in people with HIV and Contraception, run by CONRAD at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
HIV, Contraception
What is being tested?
TFV IVR and TFV/LNG IVR
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
86 participants
Where
2 sitesin 2 countries
Study dates
Oct 2014to Dec 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Eastern Virginia Medical School

    Norfolk, Virginia, 23507

Other trials in United States

Dominican Republic1 site

  • Profamilia

    Santo Domingo, Dominican Republic

Other trials in Dominican Republic

About this study

Official title: Phase I One-Month Safety, Pharmacokinetic, Pharmacodynamic, and Acceptability Study of Intravaginal Rings Releasing Tenofovir and Levonorgestrel or Tenofovir Alone

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
HIV, Contraception
Being tested
TFV IVR, TFV/LNG IVR, Placebo IVR
Keywords
HIV, LNG, IVR, Contraception, Prevention

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TFV IVRDrug

    Also called Tenofovir Intravaginal Ring

  • TFV/LNG IVRDrug

    Also called Tenofovir Levonorgestrel Intravaginal Ring

  • Placebo IVROther

    Also called Placebo Intravaginal Ring

Study groups in NCT02235662
Study groupRoleWhat they receive
TFV IVRExperimentalTFV 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.
Receives: Drug: TFV IVR
TFV/LNG IVRExperimentalTFV/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.
Receives: Drug: TFV IVR; Drug: TFV/LNG IVR
Placebo Intravaginal RingPlacebo comparatorIntravaginal 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.
Receives: Other: Placebo IVR

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of treatment-emergent adverse events

    Number of treatment-emergent adverse events

    Measured: IVR Day 1, 2, ~8, ~16-18; 24 hours and 1-2 weeks post-IVR insertion and 1-2 weeks after IVR removal

  2. Systemic laboratory tests

    Changes in Systemic laboratory tests

    Measured: Baseline and IVR Day ~16-18

  3. 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

    Measured: Baseline, IVR Day 2, ~8 and ~16-18

  4. 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

    Measured: Baseline and IVR Day ~16-18

  5. 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)

    Measured: Baseline and IVR Day ~16-18

  6. Microflora (semi-quantitative vaginal culture and/or unculturable bacteria)

    Changes microflora (semi-quantitative vaginal culture and/or unculturable bacteria)

    Measured: Baseline and IVR Day ~16-18

  7. Vaginal pH

    Changes in vaginal pH

    Measured: Baseline and IVR Day ~16-18

  8. Nugent Score

    Changes in Nugent Score

    Measured: Baseline and IVR Day ~16-18

Secondary outcomes (10)

  1. TFV concentrations in plasma

    TFV concentrations in plasma

    Measured: Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal

  2. TFV concentrations in cervicovaginal fluid (aspirate and swab)

    TFV concentrations in cervicovaginal fluid (aspirate and swab)

    Measured: 1, 2, 4 or 8 hours post-IVR insertion (randomized time point); IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal

  3. TFV concentrations in genital tissue (biopsy)

    TFV concentrations in genital tissue (biopsy)

    Measured: IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)

  4. Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs)

    TFV-DP concentrations in PBMCs

    Measured: IVR Day ~16-18

  5. TFV-DP concentrations in genital tissue (biopsy)

    TFV-DP concentrations in genital tissue (biopsy)

    Measured: IVR Day 2, ~16-18; 24 or 72 hours post-IVR removal (randomized time point)

  6. LNG concentration in blood (including SHBG)

    LNG concentration in blood (including SHBG)

    Measured: Baseline; 1, 2, 4 and 8 hrs post-IVR insertion; IVR Day 2, ~8, ~16-18; 24 hours post-IVR removal

  7. LNG concentration in vaginal secretions (swabs)

    LNG concentration in vaginal secretions (swabs)

    Measured: Baseline; IVR Day~8

  8. LNG concentration in cervical mucus

    LNG concentration in cervical mucus

    Measured: IVR Day ~8, ~16-18; 24 hours post-IVR removal

  9. Weight of returned IVRs

    Weight of returned IVRs

    Measured: IVR Day ~16-18 (post-removal)

  10. Amount of drug remaining in returned IVRs

    Amount of drug remaining in returned IVRs

    Measured: IVR Day ~16-18 (post-removal)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionDec 2015
  4. Study completionDec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02235662
Sponsor's protocol ID
A13-128
Status last verified
Jan 2016
First submitted
14 Jul 2014
Last updated
11 Jan 2016
Results posted
No
Data monitoring committee
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TFV IVR and TFV/LNG IVR in people with HIV and Contraception, run by CONRAD at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Dominican Republic. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02235662, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in