HealthyPhase 1NCT02357602

Dose Proportionality of TFV-DP After a Single Dose of GS-7340 in Women

A Phase 1 study testing GS-7340 in people with Healthy, run by University of North Carolina, Chapel Hill 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

Purpose: The purpose of this study is to characterize the dose-proportionality in the distribution of tenofovir alafenamide (TAF) and tenofovir (TFV) in plasma and mucosal tissues, and TFV-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) and mucosal tissues of healthy female subjects following a… Read more about this study

Who is it for?: Ages 18 to 49 years, women onlyHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: GS-7340
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: Mar 2015to Nov 2016
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 49 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Healthy pre-menopausal female subjects between the ages of 18 and 49 years, inclusive on the date of screening, with an intact gastrointestinal tract, uterus, and cervix.
All subjects must have an estimated calculated creatinine clearance (eCcr) of at least 80 mL/min
All subjects must have negative pregnancy tests, and be using an acceptable form of birth control
Body Mass Index (BMI) of approximately 18 to 34 kg/m²; and a total body weight > 45 kg (99 lbs).
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

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Subject must have documentation of a normal pap smear within 36 months of the screening visit, no procedures for abnormal cervical/vaginal pathology in the last six months, at least one prior gynecological visit as part of subject's routine medical history.
Subject must be willing to abstain from sexual intercourse, douching, and all intravaginal and intrarectal objects and products for at least 72 hours prior to Day 1 until study completion.
Subject must be HIV-1 and Hepatitis B surface antigen negative
Subject must not be actively involved in the conception process.
Subject must be able to swallow pills and have no allergies to any component of the study products

Who cannot join

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
Subjects with a history of hysterectomy
Subjects who are pregnant, possibly pregnant or lactating
Subjects with a presence of vaginal discharge or genital bleeding at screening
History of febrile illness within five days prior to first dose.
Any condition possibly affecting drug absorption (eg, gastrectomy).

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A positive urine drug screen.
A positive result for HIV, Hepatitis B or C
An untreated-positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at screening, or symptomatic bacterial vaginosis.
Any laboratory chemistry or hematology result Grade 2 or greater according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) Laboratory Grading Tables
Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
History of regular alcohol consumption exceeding study limits
Participation in a clinical trial involving vaginal or rectal biopsies within 6 months preceding the first dose of trial medication.
Use of prescription or nonprescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial medication and unable to avoid use during the study period until after the last sample is collected.
Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Allergy to lidocaine or Monsel's solution.
Allergy to latex.
Abnormal pap smear in the past 36 months
Any degree of ectopy or abnormality evident during the pelvic exam at screening.
Any condition which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately.
Unwilling or unable to comply with the dietary and concomitant drug restrictions in regard to study drug administration as outlined in the study procedures and prohibited medications sections.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: Dose Proportionality of TFV-DP in Mucosal Tissue, and Endogenous Nucleotide Quantification, After a Single Dose of GS-7340 in Women

Purpose:

The purpose of this study is to characterize the dose-proportionality in the distribution of tenofovir alafenamide (TAF) and tenofovir (TFV) in plasma and mucosal tissues, and TFV-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) and mucosal tissues of healthy female subjects following a single oral dose of GS-7430 at 5mg, 10mg, and 25mg.

Read the detailed description

Participants:

This study will consist of approximately 24 premenopausal healthy volunteer women between 18-49 years of age with an intact cervix, uterus, and gastrointestinal tract. Women will be enrolled in the study within 42 days of screening depending on the timing of their menstrual cycle in comparison to the screening visit, and then will be on study for 14 days, with follow-up 1-14 days after the end of study sampling. All study visits will be conducted in the North Carolina Translational and Clinical Sciences (NCTraCS) Clinical Translational Research Center (CTRC) at the University of North Carolina at Chapel Hill.

Procedures (methods):This is a Phase 1, single center, open-label, dose-ranging pharmacokinetic study of TFV and TFV-DP mucosal tissue concentrations measured after a single dose of GS-7340. Each arm is divided into three dosing groups: 5, 10, or 25mg. Participants will take a single dose of study drug within 7-14 days following the end of the subjects' menstrual period. Participants will be sequentially assigned to one of the three TAF doses and four biopsy schedules. Two women from each of the dosing groups will be assigned to one of four biopsy schedules for a total of 8 women per dosing group. Samples of blood plasma, cervicovaginal fluid (CVF), cervical tissue, vaginal tissue, and rectal tissue will be collected from participants at varying time points over the 14 days post-dose. Subjects will return to clinic within 14 days after the last sampling to complete a follow-up safety visit.

Conditions: Healthy
Being tested: GS-7340
Keywords: Participants, HIV-1 negative

What participants receive

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

GS-7340Drug
Also called TAF, Tenofovir Alafenamide
Medication is supplied in 10 or 25mg tablets, so subjects will receive either 1/2 or one tablet in a single dose.

Study groups in NCT02357602
Study group	Role	What they receive
1. GS-7340 25mg	Experimental	The first 8 women on study will be assigned to take a single dose of 25mg TAF (1 tablet) orally. Receives: Drug: GS-7340
2. GS-7340 10mg	Experimental	The 2nd group of 8 women will be sequentially assigned to take a single dose of 10mg TAF (1 tablet) orally. Receives: Drug: GS-7340
3. GS-7340 5mg	Experimental	The final 8 women on study will be sequentially assigned to take a single dose of 5mg TAF (1/2 tablet) orally. Receives: Drug: GS-7340

What is being measured

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

Plasma Dose-Proportionality
To characterize the dose-proportionality in the distribution of TAF and TFV in the plasma of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
Measured: Pre-dose and 1, 3, 6, 12, 24 hours, and 3, 7, 10, and 14 days following single dose
Tissue Dose-Proportionality
To characterize the dose-proportionality in the distribution of TAF and TFV in mucosal tissues, and TFV-DP in mucosal tissues of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
Measured: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
PBMC Dose-Proportionality
To characterize the dose-proportionality in the distribution of TFV-DP in PBMCs of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
Measured: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose

Secondary outcomes (4)

Intra-subject variability in intracellular deoxyadenosine triphosphate (dATP) in peripheral blood
To determine intra-subject variability in intracellular dATP in PBMCs and ratios of TFVdp:dATP.
Measured: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
Inter-subject variability in intracellular deoxyadenosine triphosphate (dATP) in peripheral blood
To determine inter-subject variability in intracellular dATP in PBMCs and ratios of TFVdp:dATP.
Measured: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
Intra-subject variability in intracellular deoxyadenosine triphosphate (dATP) in mucosal tissues
To determine intra-subject variability in intracellular dATP in cervical, vaginal, and rectal tissues and ratios of TFVdp:dATP.
Measured: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
Inter-subject variability in intracellular deoxyadenosine triphosphate (dATP) in mucosal tissues
To determine inter-subject variability in intracellular dATP in cervical, vaginal, and rectal tissues and ratios of TFVdp:dATP.
Measured: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose

Timeline

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

Mar 2015Nov 2016

First posted6 Feb 2015 (estimated)
Study startMar 2015
Primary completionOct 2015
Study completionNov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies 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: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02357602
Sponsor's protocol ID: 14-2797
Status last verified: Nov 2016
First submitted: 14 Jan 2015
Last updated: 30 Nov 2016
Results posted: No
Data monitoring committee: Yes

Publications

Cottrell ML, Garrett KL, Prince HMA, Sykes C, Schauer A, Emerson CW, Peery A, Rooney JF, McCallister S, Gay C, Kashuba ADM. Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues. J Antimicrob Chemother. 2017 Jun 1;72(6):1731-1740. doi: 10.1093/jac/dkx064.
PubMed 28369415

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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Study at a glance

From the registry record, last updated by the sponsor on 30 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Dose Proportionality of TFV-DP in Mucosal Tissue, and Endogenous Nucleotide Quantification, After a Single Dose of GS-7340 in Women
ClinicalTrials.gov ID: NCT02357602
Acronym / sponsor ID: 14-2797
Conditions: Healthy
Keywords: Participants, HIV-1 negative
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: University of North Carolina, Chapel HillUniversity, hospital or other
Collaborators: Gilead Sciences
Study start: Mar 2015
Primary completion: Oct 2015 (actual)
Study completion: Nov 2016 (actual)
First posted: 6 Feb 2015 (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.

Purpose:

Detailed description

Participants:

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
1. GS-7340 25mg	Experimental	Drug: GS-7340The first 8 women on study will be assigned to take a single dose of 25mg TAF (1 tablet) orally.
2. GS-7340 10mg	Experimental	Drug: GS-7340The 2nd group of 8 women will be sequentially assigned to take a single dose of 10mg TAF (1 tablet) orally.
3. GS-7340 5mg	Experimental	Drug: GS-7340The final 8 women on study will be sequentially assigned to take a single dose of 5mg TAF (1/2 tablet) orally.

Who may qualify

Ages: 18 to 49 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

Healthy pre-menopausal female subjects between the ages of 18 and 49 years, inclusive on the date of screening, with an intact gastrointestinal tract, uterus, and cervix.
All subjects must have an estimated calculated creatinine clearance (eCcr) of at least 80 mL/min
All subjects must have negative pregnancy tests, and be using an acceptable form of birth control
Body Mass Index (BMI) of approximately 18 to 34 kg/m²; and a total body weight > 45 kg (99 lbs).
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.

Key exclusion criteria (22 listed)

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
Subjects with a history of hysterectomy
Subjects who are pregnant, possibly pregnant or lactating
Subjects with a presence of vaginal discharge or genital bleeding at screening
History of febrile illness within five days prior to first dose.

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
GS-7340Also: TAF, Tenofovir AlafenamideMedication is supplied in 10 or 25mg tablets, so subjects will receive either 1/2 or one tablet in a single dose.	Drug	1. GS-7340 25mg, 2. GS-7340 10mg, 3. GS-7340 5mg

Primary outcome

Plasma Dose-Proportionality
Time frame: Pre-dose and 1, 3, 6, 12, 24 hours, and 3, 7, 10, and 14 days following single dose
To characterize the dose-proportionality in the distribution of TAF and TFV in the plasma of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
Tissue Dose-Proportionality
Time frame: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
To characterize the dose-proportionality in the distribution of TAF and TFV in mucosal tissues, and TFV-DP in mucosal tissues of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
PBMC Dose-Proportionality
Time frame: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
To characterize the dose-proportionality in the distribution of TFV-DP in PBMCs of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.

4 secondary outcomes

Intra-subject variability in intracellular deoxyadenosine triphosphate (dATP) in peripheral blood
Time frame: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
Inter-subject variability in intracellular deoxyadenosine triphosphate (dATP) in peripheral blood
Time frame: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
Intra-subject variability in intracellular deoxyadenosine triphosphate (dATP) in mucosal tissues
Time frame: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
Inter-subject variability in intracellular deoxyadenosine triphosphate (dATP) in mucosal tissues
Time frame: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose

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 30 Nov 2016.
Derived from this study: PubMed 28369415Cottrell ML, Garrett KL, Prince HMA, Sykes C, Schauer A, Emerson CW, Peery A, Rooney JF, McCallister S, Gay C, Kashuba ADM. Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues. J Antimicrob Chemother. 2017 Jun 1;72(6):1731-1740. doi: 10.1093/jac/dkx064.

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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

UNC Chapel Hill

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GS-7340 in people with Healthy, 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 11 inclusion and 22 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 30 Nov 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?

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?

Plasma Dose-Proportionality (time frame: Pre-dose and 1, 3, 6, 12, 24 hours, and 3, 7, 10, and 14 days following single dose). 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 NCT02357602, 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 Nov 2016.