Evaluation of the Cellular Pharmacology of Tenofovir and Emtricitabine According to HIV Infection Status

NCT ID: NCT01040091

Last Updated: 2016-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-31

Study Completion Date

2014-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are two antiretroviral medications used for the treatment and prevention of HIV/AIDS. This study will examine how these medications are processed in the body of people who are HIV-infected, as well as in people who are HIV-uninfected.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are both nucleoside reverse transcriptase inhibitors (NRTIs), a class of medications used for the treatment and prevention of HIV/AIDS. Analyzing how the body interacts with these medications at the cellular level may lead to more effective dosing strategies for both HIV prevention and treatment. This study will examine the pharmacokinetics of TDF and FTC at the cellular level in HIV-infected people (N=20) and HIV-uninfected people (N=20). HIV-infected participants will be allowed to take part in this study only if their doctor already plans to prescribe TDF, FTC, and efavirenz (EFV) for their HIV care, regardless of their participation in this study. HIV-infected participants will receive Truvada (TDF/FTC) and EFV for the first 30 days. After Day 30, participants will continue to receive TDF, FTC, and EFV through Day 60, under the direction of their physician. HIV-infected participants will remain on their therapy throughout the study as part of their HIV care. HIV-uninfected volunteers will receive 30 days of Truvada (TDF/FTC).

The study duration is 60 days. Study visits will occur at baseline and on Days 1, 3, 7, 20, 30, and 60. At most study visits, participants will undergo blood and urine collection for pharmacology studies, a medication history review, and an adverse effects questionnaire. HIV-uninfected participants will also attend two additional study visits at Days 35 and 45 - while off study medication - for blood and urine collection, adverse effects questionnaires, and a medication history review. At varying study visits during the first 30 days, all participants will undergo one rectal biopsy, female participants will undergo one cervical cell and fluid sampling procedure, and male participants will provide one semen sample. In addition to the collections from enrolled participants, study researchers will also analyze previously collected and stored blood samples from participants in the "Chemoprophylaxis for HIV Prevention in Men (iPrEx)" study, which examined the use of TDF and FTC for the prevention of HIV in men who have sex with men (MSM).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

HIV Seronegativity Treatment Experienced

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

HIV-Infected Participants

HIV-infected participants will receive FTC, TDF, and EFV for 60 days by prescription from their physicians. Participants will receive Truvada (FTC/TDF) and EFV for the first 30 days. After Day 30, participants may switch to the TDF/FTC/EFV co-formulation through Day 60 as directed by their physician.

Group Type ACTIVE_COMPARATOR

Emtricitabine (FTC)

Intervention Type DRUG

200 mg once a day

Tenofovir disoproxil fumarate (TDF)

Intervention Type DRUG

300 mg once a day

Efavirenz (EFV)

Intervention Type DRUG

600 mg once a day

Truvada

Intervention Type DRUG

200 mg emtricitabine + 300 mg TDF once a day

HIV-Uninfected Participants

HIV-uninfected participants will receive Truvada (FTC/TDF) for 30 days.

Group Type ACTIVE_COMPARATOR

Truvada

Intervention Type DRUG

200 mg emtricitabine + 300 mg TDF once a day

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Emtricitabine (FTC)

200 mg once a day

Intervention Type DRUG

Tenofovir disoproxil fumarate (TDF)

300 mg once a day

Intervention Type DRUG

Efavirenz (EFV)

600 mg once a day

Intervention Type DRUG

Truvada

200 mg emtricitabine + 300 mg TDF once a day

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Ability to provide informed consent
* Ability to comply with the study procedures


* HIV-infected adults (HIV documented in medical record or by the primary clinician)
* Clinician/participant plan to initiate TDF/FTC/EFV therapy and agree to separate TDF/FTC and EFV prescriptions for the initial 30 days of the study
* Ability to provide informed consent
* Ability to comply with the study procedures

Exclusion Criteria

* Positive screening test for HIV infection
* Positive screening test for hepatitis B (HBV) infection
* Pregnant or planning to become pregnant in the 3 months after study entry
* Breastfeeding
* If sexually active and fertile (no tubal ligation or hysterectomy), refusal to use two forms of birth control (e.g., condom and hormonal birth control) during the 60-day study
* Estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m\^2 by the Modification of Diet in Renal Disease (MDRD) method
* Albuminuria (greater than 30 mg urine albumin per g of urine creatinine)
* Blood donation within 56 days of the screening visit
* Any grade I or higher abnormality in hemoglobin, platelets, serum phosphorous, and lipase on the screening visit; grade I abnormalities in other labs will be evaluated on a case by case basis (using DAIDS criteria)
* Any greater than grade I abnormality in screening laboratory tests (using DAIDS grading criteria)
* Medical history of chronic uncontrolled high blood pressure equal to or above 140/90 mm Hg
* Use of any investigational medication in the 30 days before study entry
* Daily anticoagulant therapy (daily aspirin or non-steroidal anti-inflammatory drugs \[NSAIDs\] will be allowed if discontinued for 1 week prior to the rectal biopsy)
* Any nephrotoxic concomitant medication (e.g., aminoglycosides, cyclosporine, cidofovir, foscarnet, amphotericin B)
* Active recreational drug or alcohol abuse
* Any concomitant medication (or herbal product) that, in the opinion of the investigators, would interfere with the study outcomes (acceptable medications include acetaminophen, occasional ibuprofen/NSAID, vitamins, and birth control pills)
* History of pathologic bone fractures
* Any chronic or acute medical condition that, in the opinion of the investigator, would interfere with study conditions, such as cancer, heart disease, or diabetes
* Body weight under 110 pounds


* Antiretroviral therapy in the preceding 6 months
* Pregnant or planning to become pregnant in the 3 months after study entry
* Breastfeeding
* If sexually active and fertile (no tubal ligation or hysterectomy), refusal to use two forms of birth control (e.g., condom and hormonal birth control) during the 60-day study
* Estimated GFR less than 60 mL/min/1.73 m\^2 by the MDRD method
* Albuminuria (greater than 30 mg urine albumin per g of urine creatinine)
* Greater than a grade II abnormality in hemoglobin or platelets. Greater than a grade II abnormality in other clinical chemistry or hematology tests that, in the opinion of the investigators (principal investigator, study coordinator, and study physician) and primary clinician, would preclude participation in the study. DAIDS grading criteria will be used.
* Use of any investigational medication in the 30 days before study entry
* Daily anticoagulant therapy (daily aspirin or NSAIDs will be allowed if discontinued for 1 week prior to the rectal biopsy)
* Any nephrotoxic concomitant medication (e.g., aminoglycosides, cyclosporine, cidofovir, foscarnet, amphotericin B)
* Any concomitant medication (or herbal product) that, in the opinion of the investigators, would interfere with the study outcomes (acceptable medications include acetaminophen, occasional ibuprofen/NSAID, vitamins, and birth control pills)
* Any chronic or acute medical condition that, in the opinion of the investigator, could lead to emergent health complications, or could interfere with the participant's ability to follow study procedures
* Body weight under 110 pounds
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Peter L. Anderson, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Colorado CTRC CRS

Aurora, Colorado, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Castillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng JH, Gardner EM, Liu A, Glidden DV, Grant R, Hosek S, Wilson CM, Bushman LR, MaWhinney S, Anderson PL. Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6692-6697. doi: 10.1128/AAC.01017-16. Print 2016 Nov.

Reference Type DERIVED
PMID: 27572401 (View on PubMed)

Chen X, Castillo-Mancilla JR, Seifert SM, McAllister KB, Zheng JH, Bushman LR, MaWhinney S, Anderson PL. Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5387-92. doi: 10.1128/AAC.01019-16. Print 2016 Sep.

Reference Type DERIVED
PMID: 27353267 (View on PubMed)

Castillo-Mancilla JR, Meditz A, Wilson C, Zheng JH, Palmer BE, Lee EJ, Gardner EM, Seifert S, Kerr B, Bushman LR, MaWhinney S, Anderson PL. Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals. J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):495-501. doi: 10.1097/QAI.0000000000000529.

Reference Type DERIVED
PMID: 25763783 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://clinicaltrials.gov/ct2/show/NCT00458393

Click here for the "Chemoprophylaxis for HIV Prevention in Men (iPrEx)" ClinicalTrials.gov study record.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

10817

Identifier Type: REGISTRY

Identifier Source: secondary_id

U01 Anderson

Identifier Type: -

Identifier Source: org_study_id