HivPhase 4NCT03350672

Validation of a Urine Assay to Measure Tenofovir Levels in Patients Taking Tenofovir Alafenamide

A Phase 4 study testing FTC/TAF in people with Hiv, run by Philadelphia Fight at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Hiv
What is being tested?: FTC/TAF
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 1 siteUnited States
Study dates: 16 Nov 2017to 1 May 2018
Phase: Phase 4
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 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Cohort 1(a \& b) Inclusion Criteria:

Age 18 or older at the time of signed informed consent
Not currently taking commercial Truvada for PrEP or any other investigational, oral medication for the purpose of HIV PrEP
Willing and able to independently provide written informed consent
Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test

Cohort 1(a \& b) Exclusion Criteria:

Evidence of acute or chronic hepatitis B infection at the time of screening
Other clinically significant acute or chronic medical condition, including severe infections requiring treatment such as tuberculosis, as determined by the study investigator
Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) / (72 x serum creatinine)
History of bone fractures not explained by trauma
Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS grading system
Known allergy/sensitivity to the study drug or its components
Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
Any other clinical condition or prior therapy that, in the opinion of the Principal Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Cohort 2 Inclusion Criteria:

Age 18 or older at the time of signed informed consent
Willing and able to independently provide written informed consent
Last viral load < 20 copies/mL within the last four weeks of screening
Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6 months
Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months

Cohort 2 Exclusion Criteria:

Other clinically significant acute or chronic medical condition, including severe infections requiring treatment such as tuberculosis, as determined by the study investigator
Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) / (72 x serum creatinine)
Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS grading system
Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
Any other clinical condition or prior therapy that, in the opinion of the Principal Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

Philadelphia FIGHT
Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Pre-exposure prophylaxis (PrEP) with Truvada™ (tenofovir/emtricitabine), in which an HIV-uninfected individual at high risk for contracting HIV takes antiretroviral medications (one pill daily) to maintain blood and genital drug levels sufficient to prevent HIV-1 acquisition, has been validated in several large international trials that have included men who have sex with men and transgender women, heterosexual men and women, and people who use injection drugs, as a potential HIV-1 prevention strategy. HIV prevention interventions such as this, if adequately disseminated and implemented broadly, may help to curb new HIV infections, reduce HIV-associated morbidity and mortality, and reduce health disparities in HIV rates among the most at-risk individuals. Assuring adherence to a daily dose of PrEP is critical for effective protection against HIV infection. A urine-based test to measure PrEP medication levels in the body represents a non-invasive technique to assess adherence and ultimately improve PrEP's protective ability.

TAF/FTC (Descovy™) is a new medication under study for HIV prevention to see if it is as effective as Truvada™. This study is testing whether a urine test can detect this medication in urine.

Read the detailed description

Primary Objectives:

1a) To determine how long TFV is excreted in the urine in patients at steady state of TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. Morning urine and plasma samples will be collected starting the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of consistent adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV. A correction analysis similar to that below will also be assessed in this cohort.

1b) To determine how long TFV is excreted in the urine in patients who have taken one dose of TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to ensure adherence. Morning urine and plasma samples will be collected starting the day the dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of inconsistent or intermittent (1 day only) adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV. Investigators will also examine the correct urine TFV values for inter-subject variability by assessing which measure (specific gravity, urine creatinine, pH) will maximize the correlation between urine TFV levels and an ideal line of elimination.

Secondary Objective:

To determine the expected urine tenofovir levels in a population of HIV-positive patients on TAF-based regimens. A cross-sectional analysis of ten HIV-positive patients with undetectable viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine and plasma samples will be collected at one time point to determine urine TFV concentration in the setting of steady state dosing in HIV patients with presumably very good adherence to medication, and compared to a historical cohort of patients on TDF-based regimens.

Conditions: Hiv
Being tested: FTC/TAF
Keywords: HIV prevention, PrEP, Descovy
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FTC/TAFDrug
Participants in cohorts 1a\&b will be administered FTC/TAF for 1 to 7 consecutive days and then be followed clinically for 6 to 14 days. Cohort 2 will participate in a 1 time blood and urine collection.

Study groups in NCT03350672
Study group	Role	What they receive
Cohort 1a	Experimental	Age 18 or older at the time of signed informed consent * Not currently taking commercial FTC/TDF for PrEP or any other investigational, oral medication for the purpose of HIV PrEP * Willing and able to independently provide written informed consent * Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test Receives: Drug: FTC/TAF
Cohort 1b	Experimental	Age 18 or older at the time of signed informed consent * Not currently taking commercial FTC/TDF for PrEP or any other investigational, oral medication for the purpose of HIV PrEP * Willing and able to independently provide written informed consent * Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test Receives: Drug: FTC/TAF
Cohort 2	Active comparator	* Age 18 or older at the time of signed informed consent * Willing and able to independently provide written informed consent * Last viral load < 20 copies/mL within the last four weeks of screening * Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6 months * Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months Receives: Drug: FTC/TAF

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Urine Samples Containing TFV in Concentrations Greater Than or Equal to 1000ng/mL From the 7-dose Cohort (1b).
Cohort 1b: To determine how long TFV is excreted in the urine in patients at steady state of TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10 days). Urine samples collected from all participants were analyzed via LC-MS/MS for tenofovir concentrations.
Measured: Daily for a maximum of 10 days
Percent of Urine Samples Containing TFV Levels Greater Than or Equal to 1000ng/mL in the Single Dose Cohort (1a).
To determine how long TFV is excreted in the urine in patients who have taken one dose of TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of inconsistent or intermittent (1 day only) adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV.
Measured: 7 days
Percentage of Urine Samples Containing Tenofovir at Concentrations Greater Than or Equal to 1000ng/mL (Cohort 2).
To determine the expected urine tenofovir levels in a population of patients living with HIV on TAF-based regimens. A cross-sectional analysis of ten patients living with HIV with undetectable viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine samples will be collected at one time point to determine urine TFV concentration in the setting of steady state dosing in HIV patients with presumably very good adherence to medication.
Measured: 1 day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Nov 20171 May 2018

First posted22 Nov 2017
Study start16 Nov 2017
Primary completion29 Mar 2018
Study completion1 May 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.
Publications (1)Papers the sponsor has linked to this study.
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 4
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: 1a) Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. 1b) Ten healthy subjects will be given one daily dose of TAF/FTC under direct observation to ensure adherence. Morning (not first morning) urine and plasma samples will be collected starting the day the dose is given (1 hr post-dose) and every day thereafter for 6 days. 2\) Ten HIV-positive patients who have had undetectable viral loads for greater than 12 weeks (and a recent undetectable viral load in the previous 4 weeks) on an antiretroviral regimen containing TAF/FTC (i.e. Genvoya™, Odefsey™, or Descovy™ in combination with another HIV medication or medications) will have one-time pre-dose urine (early morning) and plasma samples drawn for tenofovir (TFV) concentration, as well as a comprehensive metabolic panel for measurement of creatinine clearance.
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03350672
Sponsor's protocol ID: PhiladelphiaFight
Status last verified: Sep 2021
First submitted: 14 Nov 2017
Last updated: 30 Sep 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Lalley-Chareczko L, Hiserodt E, Moorthy G, Zuppa A, Mounzer K, Koenig H. Urine Assay to Measure Tenofovir Concentrations in Patients Taking Tenofovir Alafenamide. Front Pharmacol. 2020 Mar 19;11:286. doi: 10.3389/fphar.2020.00286. eCollection 2020.
PubMed 32265700

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Hiv trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Validation of a Urine Assay to Measure Tenofovir Levels in Patients Taking Tenofovir Alafenamide
ClinicalTrials.gov ID: NCT03350672
Acronym / sponsor ID: PhiladelphiaFight
Conditions: Hiv
Keywords: HIV prevention, PrEP, Descovy
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Philadelphia FightUniversity, hospital or other
Collaborators: Gilead Sciences
Study start: 16 Nov 2017 (actual)
Primary completion: 29 Mar 2018 (actual)
Study completion: 1 May 2018 (actual)
First posted: 22 Nov 2017 (actual)
Results: Posted 30 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

TAF/FTC (Descovy™) is a new medication under study for HIV prevention to see if it is as effective as Truvada™. This study is testing whether a urine test can detect this medication in urine.

Detailed description

Primary Objectives:

Secondary Objective:

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: 1a) Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. 1b) Ten healthy subjects will be given one daily dose of TAF/FTC under direct observation to ensure adherence. Morning (not first morning) urine and plasma samples will be collected starting the day the dose is given (1 hr post-dose) and every day thereafter for 6 days. 2) Ten HIV-positive patients who have had undetectable viral loads for greater than 12 weeks (and a recent undetectable viral load in the previous 4 weeks) on an antiretroviral regimen containing TAF/FTC (i.e. Genvoya™, Odefsey™, or Descovy™ in combination with another HIV medication or medications) will have one-time pre-dose urine (early morning) and plasma samples drawn for tenofovir (TFV) concentration, as well as a comprehensive metabolic panel for measurement of creatinine clearance.

Arm	Type	Receives
Cohort 1a	Experimental	Drug: FTC/TAFAge 18 or older at the time of signed informed consent * Not currently taking commercial FTC/TDF for PrEP or any other investigational, oral medication for the purpose of HIV PrEP * Willing and able to independently provide written informed consent * Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test
Cohort 1b	Experimental	Drug: FTC/TAFAge 18 or older at the time of signed informed consent * Not currently taking commercial FTC/TDF for PrEP or any other investigational, oral medication for the purpose of HIV PrEP * Willing and able to independently provide written informed consent * Tests HIV negative at time of screening using rapid HIV antibody test or serum antibody/antigen 4th generation HIV test
Cohort 2	Active comparator	Drug: FTC/TAF* Age 18 or older at the time of signed informed consent * Willing and able to independently provide written informed consent * Last viral load < 20 copies/mL within the last four weeks of screening * Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6 months * Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

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
FTC/TAFParticipants in cohorts 1a\&b will be administered FTC/TAF for 1 to 7 consecutive days and then be followed clinically for 6 to 14 days. Cohort 2 will participate in a 1 time blood and urine collection.	Drug	Cohort 1a, Cohort 1b, Cohort 2

Primary outcome

Percentage of Urine Samples Containing TFV in Concentrations Greater Than or Equal to 1000ng/mL From the 7-dose Cohort (1b).
Time frame: Daily for a maximum of 10 days
Cohort 1b: To determine how long TFV is excreted in the urine in patients at steady state of TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10 days). Urine samples collected from all participants were analyzed via LC-MS/MS for tenofovir concentrations.
Percent of Urine Samples Containing TFV Levels Greater Than or Equal to 1000ng/mL in the Single Dose Cohort (1a).
Time frame: 7 days
To determine how long TFV is excreted in the urine in patients who have taken one dose of TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to ensure adherence. Morning urine samples will be collected starting the day the dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample collection). This will allow for the assessment of the length of time TFV can be measured in the urine after last dose is taken (the "lookback" period) in the context of inconsistent or intermittent (1 day only) adherence, as well as to determine how many days a patient has been off drug if a urine specimen has no detectable TFV.
Percentage of Urine Samples Containing Tenofovir at Concentrations Greater Than or Equal to 1000ng/mL (Cohort 2).
Time frame: 1 day
To determine the expected urine tenofovir levels in a population of patients living with HIV on TAF-based regimens. A cross-sectional analysis of ten patients living with HIV with undetectable viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine samples will be collected at one time point to determine urine TFV concentration in the setting of steady state dosing in HIV patients with presumably very good adherence to medication.

Results and safety

Results posted to the registry on 30 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 2	17	10
Cohort 1a	10	10
Cohort 1b	10	10

Primary outcome: Percentage of Urine Samples Containing TFV in Concentrations Greater Than or Equal to 1000ng/mL From the 7-dose Cohort (1b).

Time frame: Daily for a maximum of 10 days. Number. Unit: percentage of urine samples

Measure	Cohort 1b n = 10
Day 0 post dosing	100
Day 1 post dosing	80
Day 2 post dosing	80
Day 3 post dosing	80
Day 4 post dosing	30
Day 5 post dosing	30
Day 6 post dosing	20
Day 7 post dosing	20

Population analysed: 10 samples were collected each day during the sampling period (1 per participant).

Primary outcome: Percent of Urine Samples Containing TFV Levels Greater Than or Equal to 1000ng/mL in the Single Dose Cohort (1a).

Time frame: 7 days. Number. Unit: percentage of urine samples

Measure	Cohort 1a n = 10
Day 0 post dosng	60
Day 1 post dosing	60
Day 2 post dosing	30
Day 3 post dosing	20
Day 4 post dosing	0
Day 5 post dosing	0
Day 6 post dosing	10

Population analysed: 10 urine samples collected on each of 7 collection days (1 per participant).

Primary outcome: Percentage of Urine Samples Containing Tenofovir at Concentrations Greater Than or Equal to 1000ng/mL (Cohort 2).

Time frame: 1 day. Number. Unit: percentage of urine samples

Measure	Cohort 2 n = 10
Value	100

Adverse events

Time frame: Beginning after first dose and extending through completion of the study (Cohort 1a = 7 days; Cohort 1b = 10 days; Cohort 2 = only AEs related to blood draw collected).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 2	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Cohort 1b	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Cohort 1a	0 of 10 (0%)	0 of 10 (0%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 32265700Lalley-Chareczko L, Hiserodt E, Moorthy G, Zuppa A, Mounzer K, Koenig H. Urine Assay to Measure Tenofovir Concentrations in Patients Taking Tenofovir Alafenamide. Front Pharmacol. 2020 Mar 19;11:286. doi: 10.3389/fphar.2020.00286. eCollection 2020.
Individual participant dataSharing planned: No

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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing FTC/TAF in people with Hiv, run by Philadelphia Fight 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?

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 30 Sep 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?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 30 Sep 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?

Percentage of Urine Samples Containing TFV in Concentrations Greater Than or Equal to 1000ng/mL From the 7-dose Cohort (1b). (time frame: Daily for a maximum of 10 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03350672, which also lists 1 linked publication.

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 30 Sep 2021.