Pharmacokinetic Study in Healthy VolunteersTAILNCT01326221
Single Dose Truvada in HIV-negative Men and Women
An observational study of Pharmacokinetic Study in Healthy Volunteers, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
This open-label, non-blinded, pharmacokinetic (PK) study will assess both tenofovir and emtricitabine (components of Truvada) concentrations within genital tract of male and females after a single dose of Truvada®. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetic Study in Healthy Volunteers
- What is being tested?
- tenofovir + emtricitabine
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to May 2009
- Phase
- Observational
- 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 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Twelve adult (18 years or older) healthy volunteers will be recruited to participate in the study. A total of 6 men and 6 women will be enrolled. Subjects of all races and ethnicities may participate, provided they meet study inclusion/exclusion criteria.
Who may be able to join
- Must be above 18 years of age and less than 50 years of age
- Able and willing to provide written informed consent to take part in the study
- Able and willing to provide adequate information for locator purposes
- Must be in good general health by volunteer history without any clinically significant systemic disease, full physical examination including blood pressure and pulse rate measurement and clinical laboratory tests
- HIV-1 status antibody negative as documented at screening
- Able to comply with all study procedures throughout the duration of study participation
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- Able to comply with Lifestyle Guidelines throughout the duration of study participation
- (Males Only)
- Willing to abstain from any sexual activity including intercourse, masturbation, oral contact with the rectum, and insertion of anything per rectum for the entire duration of the study period.
- Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight > 50 kg (110 lbs).
- (Females Only)
- Must be pre-menopausal
- Must have an intact uterus and cervix
- Must have a negative serum pregnancy test at screening
- Must have negative urine pregnancy tests at day 7 and day 14
- Must have regular menstrual cycles (minimum of 26 and maximum of 35 days)
- Must be at least 2 months since last pregnancy outcome and have had at least two spontaneous menses
- Body Mass Index (BMI) of approximately 18 to 30 kg/m2; and a total body weight > 50 kg (110 lbs).
- Must abstain from use of intravaginal products including tampons, spermicides, lubricants, vaginal hygiene products, diaphragms, and cervical caps, for 72 hours prior to the baseline study visit and through 21 days after the baseline study visit.
- Must abstain from any sexual activity including intercourse, oral contact with the female genitalia, masturbation, and penetration of the vagina by fingers, tampons, sex toys, or any other objects for 72 hours prior to the baseline study visit (Day 0) and through 19 days after the baseline study visit.
Who cannot join
- HIV positive at screening
- A positive result for Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (HbcAb) screening tests or anti-hepatitis C virus serology (as determined by multi-antigen EIA)
- Active infection at the time of entry
- Active sexually transmitted disease(s)
- History of abnormal bleeding or bruising
- History of kidney disease
Show all 28Show fewer
- History of alcoholism or drug abuse
- History of significant gastrointestinal bleeding
- History of severe or recent cardiac or pulmonary event
- Use of prescription or non-prescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the baseline study visit day.
- Use of herbal supplements within 14 days of the baseline study visit day.
- Treatment with an investigational drug within 4 months preceding the baseline study visit day.
- Unwillingness to refrain from chronic use of aspirin and NSAIDS
- > Grade 2 laboratory abnormality
- Any other clinical condition or therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.
- Unwilling or unable to comply with the lifestyle guidelines for the entire duration of study participation. The lifestyle guidelines are outlined in Appendix A.
- Allergy to local anesthetics (lidocaine) or silver nitrate or iron-containing substances
- (Males Only)
- Active rectal infection at screen
- History of inflammatory bowel disease
- History or symptoms of gastrointestinal disease
- (Females Only)
- Currently pregnant or at risk for pregnancy (may be using Paragard® IUD, effective barrier method, female sterilization or abstinence, or be sexually active with a vasectomized partner)
- Currently breastfeeding
- Positive test for Neisseria gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis or syphilis at screen.
- Use of any hormonal contraceptives within 30 days of enrollment.
- Use of Depo-Provera within 120 days of enrollment.
- Current vaginal or urinary tract infection
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
Official title: Extracellular and Intracellular TFV/FTC Residues After a Single Dose in HIV-Negative Men and Women: Implications for Pre-exposure HIV Prophylaxis Dosing of Truvada®
This open-label, non-blinded, pharmacokinetic (PK) study will assess both tenofovir and emtricitabine (components of Truvada) concentrations within genital tract of male and females after a single dose of Truvada®. Concentrations of the active drug will be measured in blood (women and men), cervicovaginal aspirates and vaginal tissue (women only), seminal fluid and rectal tissue (men only). Samples will be obtained at 24 hours (1 day), 48 hours (2 days), 5 days, 7 days, 10 days, and 14 days post-dose. Each subject will undergo 2 biopsy days, at least 72 hours apart. Additionally, tissue samples will be evaluated ex-vivo for HIV infectivity.
Read the detailed description
An estimated 80% of HIV infections worldwide are acquired through sexual transmission.1 Viable methods of preventing the sexual transmission of HIV are urgently needed, especially in resource-poor countries. As these countries now have increased access to generic antiretroviral medications, oral administration of antiretroviral drugs as pre-exposure prophylaxis may serve as a feasible, minimally invasive mechanism of preventing the sexual transmission of HIV globally.
Antiretroviral prophylaxis with the combination of tenofovir and emtricitabine has recently been investigated by the U.S. Centers for Disease Control and Prevention in a series of studies with rhesus macaques. Researchers developed a rectal inoculation model using concentrations of Simian HIV (SIV) that were representative of HIV exposure in humans. With this model, researchers demonstrated that standard doses of tenofovir disoproxil fumarate delayed, or partially protected, animals from the acquisition of Simian HIV during a 14-week time period. In this same model, high dose tenofovir was fully protective from infection.2 However, it is unknown how concentrations in the macaque mucosal surfaces compare to that in humans. Notwithstanding, a number of clinical studies are currently investigating daily dosing of tenofovir or tenofovir with emtricitabine for pre-exposure prophylaxis.3
Since daily dosing of antiretrovirals for pre-exposure prophylaxis is not sustainable long-term, other coitally-dependent (episodic) dosing strategies are needed. However, the extent to which these drugs concentrate in tissues, and the duration of intracellular phosphate exposure after single doses, is currently unknown. This information is required to inform the potential of success with these dosing strategies.
At steady-state concentrations, the mean blood plasma half-life (t½) of tenofovir and emtricitabine are 15.9 hours and 10.7 hours, respectively. 4 However, the intracellular t½ of tenofovir diphosphate and emtricitabine triphosphate are >60 hours and 39 hours, respectively.5 The long intracellular t½ of the active forms of these drugs might hold advantages for episodic dosing. However, the long t½ might also hold disadvantages in terms of the development of viral resistance mutations. This phenomenon (the development of resistance after a single dose of a long t½ drug), has been previously seen with nevirapine given during delivery to HIV-infected women to prevent mother to child transmission of HIV.6 However, these women were chronically infected, rather than newly infected, as would be the case with populations exposed to prevention strategies.
The proposed study aims to augment the information gathered in previous studies by examining intracellular and extracellular tenofovir and emtricitabine drug concentrations in various human compartments after a single dose, and to describe the potential for HIV infectivity in selected tissue samples obtained from these compartments.
- Being tested
- tenofovir + emtricitabine
- Keywords
- Truvada, tenofovir, emtricitabine, Pharmacokinetics, Healthy Volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tenofovir + emtricitabineDrug
Also called Truvada
tenofovir 300mg + emtricitabine 200mg x one dose
| Study group | Role | What they receive |
|---|---|---|
| 1 | Single dose of Truvada Receives: Drug: tenofovir + emtricitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
TFV, TFV-DP, FTC, FTC-TP in blood, CVF, cervical and vaginal and rectal tissue over 14 days
The study aims to examine intra- and extracellular tenofovir and emtricitabine concentrations in various human compartments after a single dose, and to look at the potential for HIV infectivity in tissue samples from these compartments.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2011 (estimated)
- Study startOct 2008
- Primary completionMay 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacokinetic Study in Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Angela Kashuba, PharmD, University of North Carolina, Chapel Hill
- Investigators
- Angela DM Kashuba, PharmD, Principal investigator, University of North CarolinaKristine B Patterson, MD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01326221
- Sponsor's protocol ID
- 08-0410
- Acronym
- TAIL
- Status last verified
- Oct 2012
- First submitted
- 2 Mar 2009
- Last updated
- 10 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extracellular and Intracellular TFV/FTC Residues After a Single Dose in HIV-Negative Men and Women: Implications for Pre-exposure HIV Prophylaxis Dosing of Truvada®
- ClinicalTrials.gov ID
- NCT01326221
- Acronym / sponsor ID
- TAIL / 08-0410
- Keywords
- Truvada, tenofovir, emtricitabine, Pharmacokinetics, Healthy Volunteers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Oct 2008
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 30 Mar 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.
This open-label, non-blinded, pharmacokinetic (PK) study will assess both tenofovir and emtricitabine (components of Truvada) concentrations within genital tract of male and females after a single dose of Truvada®. Concentrations of the active drug will be measured in blood (women and men), cervicovaginal aspirates and vaginal tissue (women only), seminal fluid and rectal tissue (men only). Samples will be obtained at 24 hours (1 day), 48 hours (2 days), 5 days, 7 days, 10 days, and 14 days post-dose. Each subject will undergo 2 biopsy days, at least 72 hours apart. Additionally, tissue samples will be evaluated ex-vivo for HIV infectivity.
Detailed description
An estimated 80% of HIV infections worldwide are acquired through sexual transmission.1 Viable methods of preventing the sexual transmission of HIV are urgently needed, especially in resource-poor countries. As these countries now have increased access to generic antiretroviral medications, oral administration of antiretroviral drugs as pre-exposure prophylaxis may serve as a feasible, minimally invasive mechanism of preventing the sexual transmission of HIV globally.
Antiretroviral prophylaxis with the combination of tenofovir and emtricitabine has recently been investigated by the U.S. Centers for Disease Control and Prevention in a series of studies with rhesus macaques. Researchers developed a rectal inoculation model using concentrations of Simian HIV (SIV) that were representative of HIV exposure in humans. With this model, researchers demonstrated that standard doses of tenofovir disoproxil fumarate delayed, or partially protected, animals from the acquisition of Simian HIV during a 14-week time period. In this same model, high dose tenofovir was fully protective from infection.2 However, it is unknown how concentrations in the macaque mucosal surfaces compare to that in humans. Notwithstanding, a number of clinical studies are currently investigating daily dosing of tenofovir or tenofovir with emtricitabine for pre-exposure prophylaxis.3
Since daily dosing of antiretrovirals for pre-exposure prophylaxis is not sustainable long-term, other coitally-dependent (episodic) dosing strategies are needed. However, the extent to which these drugs concentrate in tissues, and the duration of intracellular phosphate exposure after single doses, is currently unknown. This information is required to inform the potential of success with these dosing strategies.
At steady-state concentrations, the mean blood plasma half-life (t½) of tenofovir and emtricitabine are 15.9 hours and 10.7 hours, respectively. 4 However, the intracellular t½ of tenofovir diphosphate and emtricitabine triphosphate are >60 hours and 39 hours, respectively.5 The long intracellular t½ of the active forms of these drugs might hold advantages for episodic dosing. However, the long t½ might also hold disadvantages in terms of the development of viral resistance mutations. This phenomenon (the development of resistance after a single dose of a long t½ drug), has been previously seen with nevirapine given during delivery to HIV-infected women to prevent mother to child transmission of HIV.6 However, these women were chronically infected, rather than newly infected, as would be the case with populations exposed to prevention strategies.
The proposed study aims to augment the information gathered in previous studies by examining intracellular and extracellular tenofovir and emtricitabine drug concentrations in various human compartments after a single dose, and to describe the potential for HIV infectivity in selected tissue samples obtained from these compartments.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: tenofovir + emtricitabineSingle dose of Truvada |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Twelve adult (18 years or older) healthy volunteers will be recruited to participate in the study. A total of 6 men and 6 women will be enrolled. Subjects of all races and ethnicities may participate, provided they meet study inclusion/exclusion criteria.
Key inclusion criteria (20 listed)
- Must be above 18 years of age and less than 50 years of age
- Able and willing to provide written informed consent to take part in the study
- Able and willing to provide adequate information for locator purposes
- Must be in good general health by volunteer history without any clinically significant systemic disease, full physical examination including blood pressure and pulse rate measurement and clinical laboratory tests
- HIV-1 status antibody negative as documented at screening
Key exclusion criteria (28 listed)
- HIV positive at screening
- A positive result for Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (HbcAb) screening tests or anti-hepatitis C virus serology (as determined by multi-antigen EIA)
- Active infection at the time of entry
- Active sexually transmitted disease(s)
- History of abnormal bleeding or bruising
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 + emtricitabineAlso: Truvadatenofovir 300mg + emtricitabine 200mg x one dose | Drug | 1 |
Primary outcome
TFV, TFV-DP, FTC, FTC-TP in blood, CVF, cervical and vaginal and rectal tissue over 14 days
Time frame: 14 days
The study aims to examine intra- and extracellular tenofovir and emtricitabine concentrations in various human compartments after a single dose, and to look at the potential for HIV infectivity in tissue samples from these compartments.
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 10 Oct 2012.
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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.
Angela DM Kashuba, PharmD principal investigator
University of North Carolina
Kristine B Patterson, MD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pharmacokinetic Study in Healthy Volunteers, run by University of North Carolina, Chapel Hill 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 20 inclusion and 28 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 10 Oct 2012. 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.
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?
TFV, TFV-DP, FTC, FTC-TP in blood, CVF, cervical and vaginal and rectal tissue over 14 days (time frame: 14 days). 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 10 Oct 2012.