HealthyEarly Phase 1FAME-05NCT02280109
Comparison of Tenofovir Vaginal Gel and Film Formulations
A Early Phase 1 study testing Tenofovir Gel and Tenofovir Film in people with Healthy and HIV, run by CONRAD at 1 site in United States.
Trial summary
This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- What is being tested?
- Tenofovir Gel and Tenofovir Film
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2014to Dec 2015
- Phase
- Early 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
- 18 to 45 years of age (inclusive) with a history of receptive vaginal intercourse.
- HIV negative within 28 days of enrollment
- Understand and agree to local STI reporting requirements.
- Able and willing to provide written informed consent to take part in the study.
- Able and willing to provide adequate information for locator purposes.
- Availability to return for all study visits, barring unforeseen circumstances.
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- Availability to return for the second formulation dosing at the same time in the subject's menstrual cycle as when the first formulation was administered, at least 10 days before menses.
- Willing to abstain from vaginal intercourse and insertion of anything (e.g., drug, vaginal douche, personal lubricant or sex toy) in vagina for 72 hours before each study product exposure, and 10 days following study product dosing, comprising a total of 26 days of abstinence, no insertion of vaginal products/objects while participating in the study.
- Willingness to have partner(s) use condoms (must not contain Nonoxynol-9) for the duration of the study.
- Agree not to participate in other research studies involving drugs and/or medical devices.
- Negative qualitative urine pregnancy test.
- Using an effective method of contraception at enrollment.
- Willingness to remain in the research unit for up to 12 hours on each of two dosing days.
Who cannot join
- Current sexual partner known by participant to be HIV seropositive.
- Individuals who, by history, engage in condom-less intercourse with HIV-infected partners, or partners that have unknown HIV serostatus, or women who exchange sex for money, shelter, or gifts.
- Active chlamydia, gonorrhea, syphilis, trichomonas, cervicitis or PID within 8 weeks prior to enrollment.
- Individuals with active hepatitis B infection.
- Known history of genital HSV (diagnosed by either clinical or laboratory test).
- Symptomatic vaginal candidiasis or bacterial vaginosis.
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- Undiagnosed irregular uterine bleeding
- Pathology of the female genital tract,
- Individuals who are status post hysterectomy.
- History of any cervicovaginal procedure (i.e. colposcopy with cervical biopsy) within the past 2 months.
- History of cone biopsy or extensive loop electrosurgical excision procedure (LEEP), which in the judgment of the investigator may affect permeability assessment.
- Any known primary or secondary uro-genital malformations, which in the assessment of the investigator may interfere with the intended urine collection for PK studies.
- Use of vaginally administered medications within 4 week of enrollment
- Any active urinary tract infection
- By history, subjects with irregular menstrual cycles.
- At screening:
- ALT or AST greater than 1.5 X the site laboratory ULN
- Hemoglobin less than 10.0 g/dL
- Platelet count less than 100,000/mm3
- Other safety tests outside of the normal range
- Findings that are clinically significant in the opinion of the investigator
- Estimated creatinine clearance < 60 ml/min based on established nomograms
- Recent history (past 6 months) of injection drug use or alcohol use that may interfere with the study.
- Unwillingness to refrain from aspirin and NSAIDs product use for one week prior to and one week post study procedures.
- Use of warfarin or heparin.
- Use of systemic immunomodulatory medications within 4 weeks of enrollment.
- Use of product containing nonoxynol-9 within 4 weeks of enrollment.
- Use of any investigational products within 4 weeks of enrollment.
- Any other medical conditions deemed not safe for participation by the investigator.
- Any individual that is pregnant or is actively breast feeding.
- Post-menopausal defined as 12 months of amenorrhea.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University School of Medicine Division of Clinical Pharmacology
Baltimore, Maryland, 21287-5554
About this study
Official title: Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Tenofovir Vaginal Gel and Film Formulation
This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective).
Read the detailed description
This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective). Further, pharmacodynamics will be assessed using cervical tissue in an ex vivo HIV biopsy challenge, and safety will be determined by assessment of adverse events following a single dose of each formulation (secondary objective). The primary endpoint will be to determine concentrations of tenofovir (TFV) and its metabolite, tenofovir diphosphate (TFV-DP), in plasma, tissue homogenates, and cervicovaginal fluid. Secondary endpoints will be determined by assessing concentrations of HIV p24 protein from explant aliquot samples up to 21 days post-infection ex vivo, and by determination of Grade 2 or higher adverse events deemed related to study product.
Research participants will receive the first tenofovir dose formulation prior to the following sampling:
- Blood PK plasma collection will be obtained at pre-dose, 0.5, 1, 2, 4, 5, 8 and 12 hours (Day 0), 24 hours (Day 1); 48 hours (Day 2); 72 hours (Day 3); and 168 hours (Day 7) following tenofovir formulation dosing.
- Cervicovaginal fluid sampling, rectal fluid sampling, and cervicovaginal biopsy will be performed (in the sequence listed) 5 and 72 hours after dosing in all subjects. Cervicovaginal fluid and rectal fluid sampling will also be obtained at 168 hours.
Subjects will be counseled to abstain from sexual intercourse and all other insertive vaginal practices for 10 days following each administered dose (or 7 days after the last cervicovaginal sampling at 72 hours). Following a safety evaluation visit, the research participant will return to the research unit and receive a second tenofovir dose formulation followed by the same schedule of sample collection and a final safety visit. PK parameters of TFV and TFV-DP will be estimated and compared between the gel and film formulations. PK parameters will include peak concentration (Cmax), area under the concentration-time curve (AUC), time to peak concentration (Tmax), elimination half-life (t1/2). Tenofovir gel and film ex vivo pharmacodynamics will also be assessed and analyzed for correspondence to pharmacokinetics.
Visit 1 Visits 2-6 Visit 7 Visits 8-12 Visit 13
- 28 Days Day 0-7 Day 14 Day 28-35 Day 42
These studies will be carried out at The Johns Hopkins Hospital under the direction of Craig Hendrix, MD, as the Project PI.
- Being tested
- Tenofovir Gel, Tenofovir Film
- Keywords
- Tenofovir, Healthy Volunteers, HIV, pharmacokinetics of tenofovir gel and film
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir GelDrug
Also called Tenofovir disoproxil
single dose of 1% tenofovir gel (equivalent to 40 mg in 4ml's of gel)
Tenofovir FilmDrug
Also called Tenofovir disoproxil
single dose of 1.3% tenofovir film (equivalent to 40 mg)
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir Gel | Active comparator | Women will receive a single dose of tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid. Receives: Drug: Tenofovir Gel |
| Tenofovir Film | Active comparator | Women will receive a single dose of tenofovir film (1.3%;40 mg) to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid. Receives: Drug: Tenofovir Film |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma tenofovir concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing
Concentration-time plot of plasma tenofovir
Measured: 72 hours
PBMC tenofovir diphosphate concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing
Concentration-time plot of PBMC tenofovir diphosphate thru 72 hours after dosing
Measured: 72 hours
Cervical tissue tenofovir maximum concentration (Cmax) at 5 hours
Measured: 5 hours
Cervical tissue tenofovir maximum concentration (Cmax) at 72 hours
Measured: 72 hours
Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 5 hours
Measured: 5 hours
Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 72 hours
Measured: 72 hours
Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 5 hours
Measured: 5 hours
Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 72 hours
Measured: 72 hours
Rectal fluid tenofovir maximum concentration (Cmax) at 5 hours
Measured: 5 hours
Rectal fluid tenofovir maximum concentration (Cmax) at 72 hours
Measured: 72 hours
All adverse clinical and laboratory events
Categorize adverse events by treatment formulation to compare the safety of single dose tenofovir gel and film formulations
Measured: one year
Secondary outcomes (2)
Cumulative HIV p24 protein concentration from 0 to 15 days post ex-vivo infection of explant cervical tissue collected at 5 hours after dosing with tenofovir gel or film
Measured: 15 days
Cumulative HIV p24 protein concentration from 0 to 15 days post ex-vivo infection of explant cervical tissue collected at 72 hours after dosing with tenofovir gel or film
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Craig Hendrix, CONRAD
- Investigators
- Craig W Hendrix, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02280109
- Sponsor's protocol ID
- DAIDS-ES #12015
- Other IDs
- U19AI082639
- Acronym
- FAME-05
- Status last verified
- Jan 2016
- First submitted
- 21 Oct 2014
- Last updated
- 28 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Pharmacokinetics and Pharmacodynamics of Single Dose Tenofovir Vaginal Gel and Film Formulation
- ClinicalTrials.gov ID
- NCT02280109
- Acronym / sponsor ID
- FAME-05 / DAIDS-ES #12015
- Keywords
- Tenofovir, Healthy Volunteers, HIV, pharmacokinetics of tenofovir gel and film
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Nov 2014
- Primary completion
- Dec 2015 (actual)
- First posted
- 31 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective).
Detailed description
This is an open label comparative study of tenofovir gel and film in 10 healthy sexually active women without active female genital tract disorders. The women will receive a single dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and tenofovir film (1.3%;40 mg) - in a crossover study design to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective). Further, pharmacodynamics will be assessed using cervical tissue in an ex vivo HIV biopsy challenge, and safety will be determined by assessment of adverse events following a single dose of each formulation (secondary objective). The primary endpoint will be to determine concentrations of tenofovir (TFV) and its metabolite, tenofovir diphosphate (TFV-DP), in plasma, tissue homogenates, and cervicovaginal fluid. Secondary endpoints will be determined by assessing concentrations of HIV p24 protein from explant aliquot samples up to 21 days post-infection ex vivo, and by determination of Grade 2 or higher adverse events deemed related to study product.
Research participants will receive the first tenofovir dose formulation prior to the following sampling:
- Blood PK plasma collection will be obtained at pre-dose, 0.5, 1, 2, 4, 5, 8 and 12 hours (Day 0), 24 hours (Day 1); 48 hours (Day 2); 72 hours (Day 3); and 168 hours (Day 7) following tenofovir formulation dosing.
- Cervicovaginal fluid sampling, rectal fluid sampling, and cervicovaginal biopsy will be performed (in the sequence listed) 5 and 72 hours after dosing in all subjects. Cervicovaginal fluid and rectal fluid sampling will also be obtained at 168 hours.
Subjects will be counseled to abstain from sexual intercourse and all other insertive vaginal practices for 10 days following each administered dose (or 7 days after the last cervicovaginal sampling at 72 hours). Following a safety evaluation visit, the research participant will return to the research unit and receive a second tenofovir dose formulation followed by the same schedule of sample collection and a final safety visit. PK parameters of TFV and TFV-DP will be estimated and compared between the gel and film formulations. PK parameters will include peak concentration (Cmax), area under the concentration-time curve (AUC), time to peak concentration (Tmax), elimination half-life (t1/2). Tenofovir gel and film ex vivo pharmacodynamics will also be assessed and analyzed for correspondence to pharmacokinetics.
Visit 1 Visits 2-6 Visit 7 Visits 8-12 Visit 13
- 28 Days Day 0-7 Day 14 Day 28-35 Day 42
These studies will be carried out at The Johns Hopkins Hospital under the direction of Craig Hendrix, MD, as the Project PI.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir Gel | Active comparator | Drug: Tenofovir GelWomen will receive a single dose of tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid. |
| Tenofovir Film | Active comparator | Drug: Tenofovir FilmWomen will receive a single dose of tenofovir film (1.3%;40 mg) to determine the pharmacokinetics of tenofovir in the blood, cervical tissue, and cervicovaginal fluid. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 18 to 45 years of age (inclusive) with a history of receptive vaginal intercourse.
- HIV negative within 28 days of enrollment
- Understand and agree to local STI reporting requirements.
- Able and willing to provide written informed consent to take part in the study.
- Able and willing to provide adequate information for locator purposes.
Key exclusion criteria (31 listed)
- Current sexual partner known by participant to be HIV seropositive.
- Individuals who, by history, engage in condom-less intercourse with HIV-infected partners, or partners that have unknown HIV serostatus, or women who exchange sex for money, shelter, or gifts.
- Active chlamydia, gonorrhea, syphilis, trichomonas, cervicitis or PID within 8 weeks prior to enrollment.
- Individuals with active hepatitis B infection.
- Known history of genital HSV (diagnosed by either clinical or laboratory test).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir GelAlso: Tenofovir disoproxilsingle dose of 1% tenofovir gel (equivalent to 40 mg in 4ml's of gel) | Drug | Tenofovir Gel |
| Tenofovir FilmAlso: Tenofovir disoproxilsingle dose of 1.3% tenofovir film (equivalent to 40 mg) | Drug | Tenofovir Film |
Primary outcome
Plasma tenofovir concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing
Time frame: 72 hours
Concentration-time plot of plasma tenofovir
PBMC tenofovir diphosphate concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing
Time frame: 72 hours
Concentration-time plot of PBMC tenofovir diphosphate thru 72 hours after dosing
Cervical tissue tenofovir maximum concentration (Cmax) at 5 hours
Time frame: 5 hours
Cervical tissue tenofovir maximum concentration (Cmax) at 72 hours
Time frame: 72 hours
Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 5 hours
Time frame: 5 hours
Cervical tissue tenofovir diphosphate maximum concentration (Cmax) at 72 hours
Time frame: 72 hours
Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 5 hours
Time frame: 5 hours
Cervicovaginal fluid tenofovir maximum concentration (Cmax) at 72 hours
Time frame: 72 hours
Rectal fluid tenofovir maximum concentration (Cmax) at 5 hours
Time frame: 5 hours
Rectal fluid tenofovir maximum concentration (Cmax) at 72 hours
Time frame: 72 hours
All adverse clinical and laboratory events
Time frame: one year
Categorize adverse events by treatment formulation to compare the safety of single dose tenofovir gel and film formulations
2 secondary outcomes
Cumulative HIV p24 protein concentration from 0 to 15 days post ex-vivo infection of explant cervical tissue collected at 5 hours after dosing with tenofovir gel or film
Time frame: 15 days
Cumulative HIV p24 protein concentration from 0 to 15 days post ex-vivo infection of explant cervical tissue collected at 72 hours after dosing with tenofovir gel or film
Time frame: 15 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig W Hendrix, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tenofovir Gel and Tenofovir Film in people with Healthy and HIV, run by CONRAD at 1 site in United States.
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 13 inclusion and 31 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 28 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 1 site in United States. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Plasma tenofovir concentration-time curve (AUC0-72) for each product (film and gel) 0 thru 72 hours after dosing (time frame: 72 hours). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jan 2016.