HIVPhase 1HPTN066NCT01276600
Dose-Proportionality and Intra-Individual Variability of Intracellular TFV-DP and FTC-TP in Healthy Volunteers
A Phase 1 study testing Emtricitabine/tenofovir in people with HIV, run by HIV Prevention Trials Network at 2 sites in United States.
Trial summary
Describe the dose-proportionality and intra-individual variability of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) at steady-state in healthy human participants taking Truvada® (FTC 200mg/TDF 300 mg) under direct observation. Read more about this study
- Who is it for?
- Ages 18 to 44 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- Emtricitabine/tenofovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2011to Oct 2011
- 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 44 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants who meet all of the following criteria are eligible for inclusion in this study:
- 18 to 44 years of age, inclusive on the date of screening.
- Provides informed consent for the study.
- Non-reactive HIV rapid test results at the screening and enrollment visits.
- An estimated calculated creatinine clearance (eCcr) at least 70 mL/min by the Cockcroft-Gault formula where:
- eCcr (female) in mL/min = [(140 - age in years) x (weight in kg) x 0.85] / (72 x serum creatinine in mg/dL).
Show all 19Show fewer
- eCcr (male) in mL/min = [(140 - age in years) x (weight in kg)] / (72 x serum creatinine in mg/dL).
- Participants are sexually active, defined as at least one sex (vaginal or anal intercourse) act in the 30 days prior to screening.
- Participants must agree to use condoms for all coital events during study participation.
- Intensive sampling cohort only:
- Not using spermicide as a means of birth control (in conjunction with a condom or diaphragm)
- Women must:
- Be pre-menopausal
- Have regular menstrual cycles with at least 21 days between menses (unless on contraception that causes amenorrhea or irregular menses)
- Have a negative urine pregnancy test at screening and enrollment
- Be utilizing an alternative method of birth control in addition to condoms (hormonal contraceptive, diaphragm or have undergone surgical sterilization) or have a vasectomized exclusive male partner.
- Intensive sampling cohort only:
- Have a cervix
- Have documentation of a normal Pap smear within 12 months
Who cannot join
- At screening::
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 X the site laboratory ULN (upper limit of normal)
- Hemoglobin less than 10.0 g/dL
- Platelet count less than 100,000/mm3
- Serum phosphate level below site laboratory LLN (lower limit of normal)
- INR or aPTT greater than site laboratory ULN
Show all 29Show fewer
- Other safety tests (bicarbonate (HCO3), potassium (K), chloride (Cl), sodium (Na), calcium (Ca), fasting glucose) with results outside of the laboratories reference range
- 1+ or greater protein on urine dipstick testing
- 1+ or greater glucose on urine dipstick testing
- Culture-confirmed urinary tract infection
- Co-enrollment in any other HIV interventional research study (excluding behavioral only interventions) or prior enrollment in the active arm of a HIV vaccine trial.
- Clinically apparent or patient report of active skin disorders including: rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.
- Women who are pregnant or breastfeeding.
- One or more reactive HIV rapid test results at screening or enrollment, even if HIV infection is not confirmed.
- Positive hepatitis B surface antigen (HBsAg) test.
- Excessive use of alcohol (more than 4 drinks a day on a regular basis).
- Interleukin therapy; medications with significant nephrotoxic potential, including but not limited to amphotericin B, aminoglycosides, cidofovir, foscarnet and systemic chemotherapy; and medications that may inhibit or compete for elimination via active renal tubular secretion (including but not limited to probenecid).
- Participants with a history of having a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption.
- Intensive sampling cohort only:
- A positive test for syphilis, gonorrhea, or Chlamydia
- A positive test for HSV-2 (individuals with active lesions only)
- Findings consistent with bacterial vaginosis, vaginal candidiasis, or trichomonas (women only)
- History of STI within 3 months prior to enrollment
- Medications that prolong clotting time (e.g., warfarin, heparin, clopidogrel classes.)
- Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
- Clinically apparent pelvic exam finding (observed by study staff) of genital lesions, erythema, edema or any other abnormal physical or pelvic exam finding that, in the opinion of the investigator or designee, would contraindicate study participation.
- Women who have had cervical procedures (conization, LEEP procedure, cryosurgery) within the previous 6 months.
- Spermicide as a method for contraception within last 30 days
- Any other reason or condition that in the judgment of the investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins University
Baltimore, Maryland, 21205
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: Dose-Proportionality and Intra-Individual Variability of Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate In Healthy Volunteers
Describe the dose-proportionality and intra-individual variability of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) at steady-state in healthy human participants taking Truvada® (FTC 200mg/TDF 300 mg) under direct observation.
Read the detailed description
This PK study is designed to establish the dose-proportionality of TFV and FTC (serum and intracellular forms) with daily to weekly dosing. This information is essential to (1) employ drug concentration as an adherence measure in future PrEP studies, and (2) to estimate the anticipated concentration of parent and active moieties of TFV and FTC in intermittent PrEP regimens associated with full adherence to a prescribed regimen. In addition, intra-individual variability will be assessed to improve sample size estimates in future PrEP studies that use drug concentration as an adherence measure or where PK-PD correlations are planned. The dose-proportionality of intra-cellular phosphates of the two components of the study product has not previously been established. Given the complexity of movement of these drugs between body compartments (central compartment, vaginal mucosal tissue, vaginal lumen, gastrointestinal mucosal tissue, gastrointestinal lumen), into cells within these compartments, and intra-cellular phosphorylation, it is possible that non-dose proportional kinetics, such as mixed or zero-order saturable processes may be operating.
- Conditions
- HIV
- Being tested
- Emtricitabine/tenofovir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emtricitabine/tenofovirDrug
200mg of emtricitabine 300mg of tenofovir
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 1 tablet orally weekly Receives: Drug: Emtricitabine/tenofovir |
| Arm 2 | Experimental | One tablet orally twice weekly Receives: Drug: Emtricitabine/tenofovir |
| Arm 3 | Experimental | Two tablets orally twice weekly Receives: Drug: Emtricitabine/tenofovir |
| Arm 4 | Experimental | One tablet orally daily Receives: Drug: Emtricitabine/tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess dose-proportionality
Assess dose-proportionality of intracellular TFV-DP and FTC-TP from weekly to daily dosing (Arms 1-4).
Measured: 49 days
Comparison of intra-individual variability--days 28 and 35
Describe intra-individual variability in intracellular TFV-DP and FTC-TP concentrations at steady-state (comparison of Day 28 and Day 35).
Measured: Days 28 and 35
Secondary outcomes (3)
Determine relationship between pre-dose and decaying concentrations
Describe the relationship between pre-dose and decaying concentrations of TFV, FTC, and their phosphorylated derivatives (TFV-DP and FTC-TP) in blood serum, peripheral blood mononuclear cells (PBMCs), CD4+ blood cells, total tissue cells, CD4+ tissue cells, tissue homogenate, semen, and luminal fluid at steady-state (Day 35 [pre-dose] and Day 49 [decaying, greater than one half-life for TFV-DP]).
Measured: Days 35 and 49
Determine differences between men and women
Describe differences in intracellular TFV-DP and FTC-TP steady-state between men and women.
Measured: 49 days
Safety profiles
Characterize the safety profiles of four different TDF/FTC PrEP regimens
Measured: 49 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies 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
- Phase 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- HIV Prevention Trials Network
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Craig Hendrix, MD, Study chair, Johns Hopkins UniversityKristine Patterson, MD, Study chair, University of North CarolinaKenneth Mayer, MD, Study chair, Brown UniversityAdriana Andrade, MD, MPH, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276600
- Sponsor's protocol ID
- HPTN 066
- Acronym
- HPTN066
- Status last verified
- Mar 2025
- First submitted
- 12 Jan 2011
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Proportionality and Intra-Individual Variability of Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate In Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01276600
- Acronym / sponsor ID
- HPTN066 / HPTN 066
- Conditions
- HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- HIV Prevention Trials NetworkResearch network
- Study start
- Jan 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 13 Jan 2011 (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.
Describe the dose-proportionality and intra-individual variability of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) at steady-state in healthy human participants taking Truvada® (FTC 200mg/TDF 300 mg) under direct observation.
Detailed description
This PK study is designed to establish the dose-proportionality of TFV and FTC (serum and intracellular forms) with daily to weekly dosing. This information is essential to (1) employ drug concentration as an adherence measure in future PrEP studies, and (2) to estimate the anticipated concentration of parent and active moieties of TFV and FTC in intermittent PrEP regimens associated with full adherence to a prescribed regimen. In addition, intra-individual variability will be assessed to improve sample size estimates in future PrEP studies that use drug concentration as an adherence measure or where PK-PD correlations are planned. The dose-proportionality of intra-cellular phosphates of the two components of the study product has not previously been established. Given the complexity of movement of these drugs between body compartments (central compartment, vaginal mucosal tissue, vaginal lumen, gastrointestinal mucosal tissue, gastrointestinal lumen), into cells within these compartments, and intra-cellular phosphorylation, it is possible that non-dose proportional kinetics, such as mixed or zero-order saturable processes may be operating.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Emtricitabine/tenofovir1 tablet orally weekly |
| Arm 2 | Experimental | Drug: Emtricitabine/tenofovirOne tablet orally twice weekly |
| Arm 3 | Experimental | Drug: Emtricitabine/tenofovirTwo tablets orally twice weekly |
| Arm 4 | Experimental | Drug: Emtricitabine/tenofovirOne tablet orally daily |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Participants who meet all of the following criteria are eligible for inclusion in this study:
- 18 to 44 years of age, inclusive on the date of screening.
- Provides informed consent for the study.
- Non-reactive HIV rapid test results at the screening and enrollment visits.
- An estimated calculated creatinine clearance (eCcr) at least 70 mL/min by the Cockcroft-Gault formula where:
Key exclusion criteria (29 listed)
- At screening::
- Culture-confirmed urinary tract infection
- Co-enrollment in any other HIV interventional research study (excluding behavioral only interventions) or prior enrollment in the active arm of a HIV vaccine trial.
- Clinically apparent or patient report of active skin disorders including: rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.
- Women who are pregnant or breastfeeding.
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 |
|---|---|---|
| Emtricitabine/tenofovir200mg of emtricitabine 300mg of tenofovir | Drug | Arm 1, Arm 2, Arm 3, Arm 4 |
Primary outcome
Assess dose-proportionality
Time frame: 49 days
Assess dose-proportionality of intracellular TFV-DP and FTC-TP from weekly to daily dosing (Arms 1-4).
Comparison of intra-individual variability--days 28 and 35
Time frame: Days 28 and 35
Describe intra-individual variability in intracellular TFV-DP and FTC-TP concentrations at steady-state (comparison of Day 28 and Day 35).
3 secondary outcomes
Determine relationship between pre-dose and decaying concentrations
Time frame: Days 35 and 49
Determine differences between men and women
Time frame: 49 days
Safety profiles
Time frame: 49 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 25 Mar 2025.
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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 Hendrix, MD study chair
Johns Hopkins University
Kristine Patterson, MD study chair
University of North Carolina
Kenneth Mayer, MD study chair
Brown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Emtricitabine/tenofovir in people with HIV, run by HIV Prevention Trials Network at 2 sites 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 19 inclusion and 29 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 25 Mar 2025. 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. 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?
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?
Assess dose-proportionality (time frame: 49 days). The study lists 2 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 25 Mar 2025.