Pre-Exposure ProphylaxisEarly Phase 1NCT03202511
Assessment of a New "Boosting" Strategy for HIV Pre-exposure Prophylaxis in Healthy Volunteers
A Early Phase 1 study testing Probenecid Oral Tablet and Tenofovir disoproxil fumarate/Emtricitabine in people with Pre-Exposure Prophylaxis, run by Indiana University at 1 site in United States.
Trial summary
The study will be a randomized, open-label, cross-over clinical pharmacokinetic trial to investigate a strategy for probenecid "boosting" in the setting of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP). Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pre-Exposure Prophylaxis
- What is being tested?
- Probenecid Oral Tablet and Tenofovir disoproxil fumarate/Emtricitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2017to 2 Jul 2018
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18 to 55 years old healthy (as decided from a pre-enrollment screening session described above) male participants within 32% of their ideal body weight.
- Individuals who agree to refrain from taking any prescriptions medications, over-the-counter medications (including salicylates/aspirin), hormonal agents, and herbal, dietary, and alternative supplements that may interact with the metabolism of those study drugs at least 2 weeks prior to the start of the study and until study completion.
- Nonsmoker or individuals willing to refrain from smoking or use of tobacco or marijuana for at least one month prior to and until the completion of the study (the entire study lasts for approximately 49 days).
Who cannot join
- 1. Are underweight (weigh less than 52 kg or 114 lb) or overweight [body mass index (BMI) greater than 32].
- 2. Females will be excluded to reduce study variability for this first proof of concept study.
- 3. Have insufficient renal function (estimated Creatinine Clearance ≤ 90 mL/min).
- 4. Have history of current alcohol or drug abuse (more than 4 alcoholic drinks per day on a regular basis).
- 5. Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tenofovir disoproxil fumarate/ emtricitabine, probenecid).
- 6. Have taken TDF or FTC as part of pre-exposure prophylaxis within the past 6 weeks.
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- 7. Any current major illness or chronic illness such as (but not limited to) kidney disease, hepatic disease, diabetes mellitus, gout, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, chronic active hepatitis B virus (HBV) infection, or HIV.
- 8. History of anemia or any other significant hematologic disorder. 9. Have history or current gastrointestinal disorders such as persistent diarrhea or malabsorption that would interfere with the absorption of orally administered drugs.
- 10. Have a serious infection within the last week before study enrollment. 11. Have donated blood within the past two months. 12. Have blood results that do not fall in a healthy range (e.g., blood hemoglobin less than 12.0 mg/dl).
- 13. Are taking on regular basis substances that may interfere with the metabolism (breakdown) of study medications by the body, including prescription medications, over-the-counter, herbal or dietary supplements, alternative medications, or hormonal agents (i.e. oral contraceptives, intra-uterine device with hormones).
- 14. Have a life style that places subjects at a higher risk for contracting HIV during the study period (e.g. active illicit drug use, excessive alcohol drinking, sexually transmitted infection (including gonorrhea, chlamydia, syphilis, herpes, human papilloma virus) within the past one year, or having more than one sexual partner in the past 6 months).
- 15. Positive HIV antibody test. 16. Positive HBV surface antigen test. 17. Have participation in a research study or use of an investigational drug in the last one month.
- 18. Are employed or are student under supervision of any of the investigators of this study.
- 19. Cannot state a good understanding of this study including risks and requirements; are unable to follow the rules of this study.
- 20. Cannot commit the time requested for this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Clinical Research Center at University Hospital
Indianapolis, Indiana, 46202
About this study
The study will be a randomized, open-label, cross-over clinical pharmacokinetic trial to investigate a strategy for probenecid "boosting" in the setting of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP). The study will be conducted at the Indiana University Clinical Research Center. All samples will be processed and the amount of tenofovir/FTC in plasma, blood, and urine, and tenofovir diphosphate and emtricitabine in peripheral blood mononuclear cells will be determined using validated analytical methods developed by the investigators at the University of Colorado. Probenecid plasma and urine concentrations will also be measured using an in-house assay. Following completion of the study, the secondary aim will be accomplished via analysis of selected samples collected at baseline and following treatment. Those selected samples will be assessed for urinary markers of proximal tubulopathy (urine total protein, albumin, creatinine, phosphorus, retinol binding protein, and beta-2-microglobulin) and serum alkaline phosphatase, osteocalcin, procollagen type 1 N propeptide, cystatin C, and creatinine to determine if the probenecid boosting strategy does indeed lead to less potential renal and bone toxicity.
- Conditions
- Pre-Exposure Prophylaxis
- Being tested
- Probenecid Oral Tablet, Tenofovir disoproxil fumarate/Emtricitabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probenecid Oral TabletDrug
Included in arm/group descriptions.
Tenofovir disoproxil fumarate/EmtricitabineDrug
Also called TDF/FTC, Truvada
Included in arm/group descriptions.
| Study group | Role | What they receive |
|---|---|---|
| Control | Active comparator | The control phase will consist of subjects taking 600/400 mg oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) on day 1 (2 tablets) followed by 300/200 mg (1 tablet) doses on days 2 and 3. Receives: Drug: Tenofovir disoproxil fumarate/Emtricitabine |
| Treatment | Experimental | The treatment phase will consist of subjects taking 600/400 mg oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (2 tablets) along with a 2 gram oral probenecid (PRO) dose (4 tablets, 500 mg each) on day 1. Receives: Drug: Probenecid Oral Tablet; Drug: Tenofovir disoproxil fumarate/Emtricitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma TFV AUC0-INF GMR
The geometric mean ratio (GMR) of the plasma TFV area under the curve (AUC) comparing the test phase (T) to control phase (C) was assessed. PK samples were collected from 0 to 72 hours post-dose.
Measured: The first 72 hours of each phase.
PBMC TFV-DP AUC GMR
The geometric mean ratio (GMR) of the PBMC TFV-DP area under the curve (AUC) comparing the test phase (T) to control phase (C) was assessed. PK samples were collected from 0 to 72 hours post-dose.
Measured: The first 72 hours of each phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2017
- Study start23 Jun 2017
- Primary completion2 Jul 2018
- Study completion2 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pre-Exposure ProphylaxisStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Subjects will be randomly allocated to enter the study in either the control or treatment arm using a blocked design to ensure equal numbers of subjects in each sequence group (n=8, control to treatment; n=8, treatment to control). Following a washout period of at least 6 weeks, each individual will crossover to the next study phase. The randomization table will be constructed prior to subject enrollment by the Principal Investigator using the Statistical Analysis Software (SAS®) randomization procedure. In the event that an individual is withdrawn from the study, an alternate participant will replace that individual using an identical study sequence to maintain the block design. A total of 16 subjects will be initially enrolled in an effort to ensure that at least 14 subjects complete the entire study. If needed, additional subjects will be screened and enrolled until the target enrollment of n=14 subjects have completed the entire study.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zeruesenay Desta, Indiana University
- Investigators
- Brandon T Gufford, PharmD, PhD, Principal investigator, Indiana Unversity School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03202511
- Sponsor's protocol ID
- 1705315090
- Status last verified
- Apr 2021
- First submitted
- 26 Jun 2017
- Last updated
- 7 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share IPD with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of a New "Boosting" Strategy for HIV Pre-exposure Prophylaxis in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03202511
- Acronym / sponsor ID
- 1705315090
- Conditions
- Pre-Exposure Prophylaxis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 23 Jun 2017 (actual)
- Primary completion
- 2 Jul 2018 (actual)
- Study completion
- 2 Jul 2018 (actual)
- First posted
- 28 Jun 2017 (actual)
- Results
- Posted 7 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will be a randomized, open-label, cross-over clinical pharmacokinetic trial to investigate a strategy for probenecid "boosting" in the setting of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP). The study will be conducted at the Indiana University Clinical Research Center. All samples will be processed and the amount of tenofovir/FTC in plasma, blood, and urine, and tenofovir diphosphate and emtricitabine in peripheral blood mononuclear cells will be determined using validated analytical methods developed by the investigators at the University of Colorado. Probenecid plasma and urine concentrations will also be measured using an in-house assay. Following completion of the study, the secondary aim will be accomplished via analysis of selected samples collected at baseline and following treatment. Those selected samples will be assessed for urinary markers of proximal tubulopathy (urine total protein, albumin, creatinine, phosphorus, retinol binding protein, and beta-2-microglobulin) and serum alkaline phosphatase, osteocalcin, procollagen type 1 N propeptide, cystatin C, and creatinine to determine if the probenecid boosting strategy does indeed lead to less potential renal and bone toxicity.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Subjects will be randomly allocated to enter the study in either the control or treatment arm using a blocked design to ensure equal numbers of subjects in each sequence group (n=8, control to treatment; n=8, treatment to control). Following a washout period of at least 6 weeks, each individual will crossover to the next study phase. The randomization table will be constructed prior to subject enrollment by the Principal Investigator using the Statistical Analysis Software (SAS®) randomization procedure. In the event that an individual is withdrawn from the study, an alternate participant will replace that individual using an identical study sequence to maintain the block design. A total of 16 subjects will be initially enrolled in an effort to ensure that at least 14 subjects complete the entire study. If needed, additional subjects will be screened and enrolled until the target enrollment of n=14 subjects have completed the entire study.
| Arm | Type | Receives |
|---|---|---|
| Control | Active comparator | Drug: Tenofovir disoproxil fumarate/EmtricitabineThe control phase will consist of subjects taking 600/400 mg oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) on day 1 (2 tablets) followed by 300/200 mg (1 tablet) doses on days 2 and 3. |
| Treatment | Experimental | Drug: Probenecid Oral Tablet, Drug: Tenofovir disoproxil fumarate/EmtricitabineThe treatment phase will consist of subjects taking 600/400 mg oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (2 tablets) along with a 2 gram oral probenecid (PRO) dose (4 tablets, 500 mg each) on day 1. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 18 to 55 years old healthy (as decided from a pre-enrollment screening session described above) male participants within 32% of their ideal body weight.
- Individuals who agree to refrain from taking any prescriptions medications, over-the-counter medications (including salicylates/aspirin), hormonal agents, and herbal, dietary, and alternative supplements that may interact with the metabolism of those study drugs at least 2 weeks prior to the start of the study and until study completion.
- Nonsmoker or individuals willing to refrain from smoking or use of tobacco or marijuana for at least one month prior to and until the completion of the study (the entire study lasts for approximately 49 days).
Key exclusion criteria (15 listed)
- 1. Are underweight (weigh less than 52 kg or 114 lb) or overweight [body mass index (BMI) greater than 32].
- 2. Females will be excluded to reduce study variability for this first proof of concept study.
- 3. Have insufficient renal function (estimated Creatinine Clearance ≤ 90 mL/min).
- 4. Have history of current alcohol or drug abuse (more than 4 alcoholic drinks per day on a regular basis).
- 5. Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (tenofovir disoproxil fumarate/ emtricitabine, probenecid).
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 |
|---|---|---|
| Probenecid Oral TabletIncluded in arm/group descriptions. | Drug | Treatment |
| Tenofovir disoproxil fumarate/EmtricitabineAlso: TDF/FTC, TruvadaIncluded in arm/group descriptions. | Drug | Control, Treatment |
Primary outcome
Plasma TFV AUC0-INF GMR
Time frame: The first 72 hours of each phase.
The geometric mean ratio (GMR) of the plasma TFV area under the curve (AUC) comparing the test phase (T) to control phase (C) was assessed. PK samples were collected from 0 to 72 hours post-dose.
PBMC TFV-DP AUC GMR
Time frame: The first 72 hours of each phase.
The geometric mean ratio (GMR) of the PBMC TFV-DP area under the curve (AUC) comparing the test phase (T) to control phase (C) was assessed. PK samples were collected from 0 to 72 hours post-dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. We do not plan to share IPD with other researchers.
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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.
Brandon T Gufford, PharmD, PhD principal investigator
Indiana Unversity School of Medicine
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 Probenecid Oral Tablet and Tenofovir disoproxil fumarate/Emtricitabine in people with Pre-Exposure Prophylaxis, run by Indiana University 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 3 inclusion and 15 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 7 May 2021. 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?
Yes. Results are posted in the registry (first posted 7 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 TFV AUC0-INF GMR (time frame: The first 72 hours of each phase.). 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 7 May 2021.