A Phase 1 interventional study of TFV/LNG IVR and Placebo in Anti-Infective Agents, Anti-Retroviral Agents and Contraceptive Usage, sponsored by CONRAD. Completed at 2 sites in 2 countries. Open to female participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-23.
Sponsored by CONRAD · Phase 1, Interventional, and Prevention
This multi-center Phase I study is designed to characterize the safety, PK, and PD of TFV/LNG IVR to assess systemic and genital tract bioavailability in healthy women. The IVRs to be used in the study are TFV/LNG IVR (8-10mg per day/20μg per day) or placebo IVR. Samples will be obtained before, during and after 90 days of continuous or interrupted IVR use.
The purpose of this multi-center Phase I protocol, titled Phase I, 90-Day Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravaginal Rings Releasing Tenofovir and Levonorgestrel is to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the Tenofovir/Levonorgestrel Intravaginal Ring (TFV/LNG IVR).
The study will enroll healthy, non-pregnant, ovulatory, HIV-uninfected women aged 18 to 50 with a body mass index (BMI) less than 30 kg/m2, regular menstrual cycles (approximately 26-35 days) by participant report, and willing to use non-spermicidal condoms for sex and follow other study restrictions. Women will be protected from pregnancy by abstinence from vaginal intercourse or agreeing to consistently use condoms.
The enrollment goal is for approximately 60 participants to complete the study. A subset of approximately 20 women will be selected for an in-depth interview to take place during the first month of IVR use and again after 90 days of use.
Women will be randomized to one of four arms: TFV/LNG IVR (8-10mg per day/20μg per day) for 90 days (Continuous), TFV/LNG IVR (8-10mg per day/20μg per day) for 3x28 days (Interrupted), placebo IVR for 90 days (Continuous), or placebo IVR for 3x28 days (Interrupted) and will undergo blood, cervicovaginal and rectal fluid sample collections, and cervicovaginal tissue collections for PK and PD assessments before, during and after 90 days of continuous or interrupted IVR use.
132 studies on the registry are indexed under Contraception Behavior; 20 are open to participants now.
This study's enrollment of 66 is below the median of 382 across 106 interventional studies indexed under Contraception Behavior.
Browse Contraception Behavior studies →CONRAD is the lead sponsor of 39 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Note: If recently pregnant, must have had at least two spontaneous menses since pregnancy outcome
Note: Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) except for treatment of dysmenorrhea during menses. Participants may use acetaminophen on an as-needed but not daily basis during the study.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TFV/LNG IVR is an intravaginal ring 55.0 mm in diameter, consisting of two segments of polyurethane tubing with an outer cross-sectional diameter of 5.5 mm: a longer segment (135 mm) containing white to off-white TFV paste and a shorter one (34 mm) with a translucent LNG core. Used for 90 days (continuous).
Drug: 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 cross-sectional diameter of 5.5 mm: a longer segment (135 mm) containing white to off-white TFV paste and a shorter one (34 mm) with a translucent LNG core. Used for 90 days (3x28 days interrupted).
Drug: TFV/LNG IVR
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. Used for 90 days (continuous).
Drug: Placebo
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. Used for 90 days (3x28 days interrupted).
Drug: Placebo
Used for 90 days (Continuous or Interrupted)
Also known as: Tenofovir/Levonorgestrel Intravaginal Ring
Used for 90 days (Continuous or Interrupted)
Percentage of women with Treatment-emergent adverse events
Treatment-emergent adverse events (TEAEs)
Time frame: Day 90
Changes in systemic laboratory values
Systemic laboratory values
Time frame: Change from Baseline at Day 90
Changes in cervicovaginal mucosa by visual inspection
Mucosal safety
Time frame: Change from Baseline at Day 90
Changes in soluble markers
Soluble markers in cervicovaginal fluid
Time frame: Change from Baseline at Day 90
Changes in inflammatory markers in cervicovaginal tissue
Inflammatory markers in cervicovaginal tissue
Time frame: Change from Baseline at Day 90
Changes in endogenous vaginal bacteria
Endogenous vaginal bacteria in cervicovaginal fluid
Time frame: Change from Baseline at Day 90
Microbial growth
Microbial growth on returned IVRs
Time frame: Day 90
Maximum Plasma Concentrations [Cmax]
Maximum Plasma Concentrations \[Cmax\] of TFV and LNG
Time frame: Baseline, 8 hours post-IVR insertion, Day 2 or 3 or 4 (randomized time point), 10, 21, 28, 32, 42, 53, 59, 63, 73, 84, 90; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Maximum CV Fluid Concentrations
Maximum CV Fluid Concentrations of TFV
Time frame: 2 and 8 hours post-IVR insertion, Day 2 or 3 or 4 (randomized time point), 10, 21, 32, 42, 53, 63, 73, 84; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Maximum Rectal Fluid Concentrations
Maximum Rectal Fluid Concentrations of TFV
Time frame: Day 2 or 3 or 4 (randomized time point), 21, 53, 84; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Maximum CV Tissue Concentrations
Maximum CV Tissue Concentrations of TFV
Time frame: Changes from baseline at day 90; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Maximum CV Tissue Metabolite Concentrations
Maximum CV Tissue Concentrations of TFV-DP
Time frame: Changes from baseline at day 90; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Maximum Serum Concentrations of LNG
Maximum Serum Concentrations of LNG
Time frame: Baseline, 1, 2, 4, and 8 hours post-IVR insertion, Day 2 or 3 or 4 (randomized time point), 10, 21, 28, 32, 42, 53, 59, 63, 73, 84, 90; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Residual Drug Concentrations
Residual drug (TFV and LNG) in returned IVRs
Time frame: Day 90
Surrogates of contraceptive efficacy of Mucus
Surrogates of contraceptive efficacy: Cervical mucus assessment (Cervical mucus quality \[score of \>10\])
Time frame: Day 30
Surrogates of contraceptive efficacy of Sperm
Surrogates of contraceptive efficacy: Cervical mucus assessment (Sperm migration on the Simplified Slide test)
Time frame: Day 30
Ovulation
Ovulation by serum progesterone (P4)
Time frame: Changes from baseline at day 90
Follicular Development
Effect on follicular development by serum estradiol concentration
Time frame: Changes from baseline at day 90
Antiviral activity in CV Fluid--HIV
Anti-HIV-1 activity in CV fluid
Time frame: Changes from baseline at day 90
Antiviral activity in CV Fluid--HSV-2
Anti-HSV-2 activity in CV fluid
Time frame: Changes from baseline at day 90
Changes in Antiviral Activity
Comparison of HIV-1 ex vivo infection in CV tissue (EVMS only) at baseline and after 90 days of IVR use
Time frame: Changes from baseline at day 90
Bleeding Patterns
Participant self-report of bleeding
Time frame: Baseline through Day 90 of IVR use
Forgiveness--LNG
Decay of LNG during 3-day periods of non-use in interrupted regimen, and after 90 days of IVR use
Time frame: Day 32 and 63; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Forgiveness--TFV
Decay of TFV during 3-day periods of non-use in interrupted regimen, and after 90 days of IVR use
Time frame: Day 32 and 63; and 48 or 72 hours or 5 days after IVR removal (randomized time point)
Acceptability--Qualitative
Responses to key questions on acceptability and psychosocial questionnaire(s) (all participants), and feedback during in-depth interviews (subset of participants)
Time frame: Baseline, Day 28 and 90
Acceptability--IDI
Responses to key questions on acceptability and psychosocial questionnaire(s) (all participants), and feedback during in-depth interviews (subset of participants)
Time frame: During first month of IVR use and Day 90
Adherence
Percentage of participants with Discontinuations/Expulsions/Removals by self-report
Time frame: Baseline, Day 28 and 90
Antiviral activity in Rectal Fluid--HIV
Anti-HIV-1 activity in rectal fluid
Time frame: Changes from baseline at day 90
Antiviral activity in Rectal Fluid--HSV-2
Anti-HSV-2 activity in rectal fluid
Time frame: Changes from baseline at day 90
Changes in Antiviral Activity--HSV-2
Comparison of HSV-2 ex vivo infection in CV tissue (EVMS-only) at baseline and after 90 days of IVR use, as possible
Time frame: Changes from baseline at day 90
Qualitative TFV measurement
Qualitative measure of TFV in a vaginal swab
Time frame: Day 90
Adherence Marker in returned vaginal ring-analytic
Analytical measures of drug or placebo products
Time frame: Day 90
Adherence marker in returned ring--bioassay
Characterization of returned IVRs (active and placebo) via objective IVR biomarkers (e.g., residual glycerin content and bioassay) and residual drug (TFV and LNG), as feasible
Time frame: Day 90
Adherence marker in returned ring--correlation
Correlation of IVR removal scale factors and objective biomarkers of IVR use
Time frame: Day 90
Adherence marker in returned ring--correlation
Correlation of baseline user characteristics and objective biomarkers of IVR use
Time frame: Day 90
Plan to share: No
Ran from Sep 2017 to primary completion in Dec 2018, 14 months.
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This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.
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