Bioequivalence of Tenofovir and Emtricitabine Following Overencapsulation (A-TEAM)

Poor adherence to tenofovir (TDF) and emtricitabine (FTC) for Human Immunodeficiency Virus (HIV) pre-exposure prophylaxis (PrEP) is common and the leading cause of therapeutic failure. The investigators need better ways to measure adherence in patients on PrEP. This application will address the need to measure adherence by evaluating an integrated technology system, Proteus Discover, when combined with Truvada. The Proteus Sensor System (PSS) will confirm that Truvada was taken, monitor adherence in both recent and long term dosing, and provides feedback to encourage adherence. The goal of this study is to determine whether the use of the PSS with Truvada will vary the drug concentrations of FTC/TDF. Participants will have 2 study visits where they will be randomized to either start with the combined PSS with Truvada or just Truvada alone. Study participants will come to the Clinical & Translational Research Center (CTRC) in the morning and take the assigned dose and will then have blood drawn at about .25, 0.5, 1, 2, 4, 6, and 10 hours after medication is taken. Participants will then return to the CTRC for blood draws 24, 48, and 72 hours after they took the dose on the first day. The second visit will mimic the first except that the participant will take the other dose form.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics
• Intervention / Treatment: Drug: TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET [TRUVADA]; Device: Proteus Sensor System

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ambulatory 18-45 year old adults.
2. Ability to comply with study procedures

Exclusion Criteria:

1. Inability to give informed consent
2. Pregnancy or planning to become pregnant within 3 months of study completion
3. Currently breastfeeding
4. High risk of HIV-1 infection (for example: sexually active with an HIV infected partner; men who have sex with men who may engage in condom-less intercourse with HIV-infected partners or partner of unknown status during the study; males or females who exchange sex for money, shelter, or gifts; active injection drug use or during the last 12 months; newly diagnosed sexually transmitted infections in last 6 months)
5. Positive HIV+ ELISA or suspected acute HIV infection in the opinion of the clinician. (example signs and symptoms of acute HIV infection include combinations of fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy cervical or inguinal)
6. Positive hepatitis B virus (HBV) surface antigen test.
7. Uncontrolled or symptomatic bone disease or history of non-traumatic bone fractures
8. Active psychiatric illness or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements
9. Creatinine clearance < 60 ml/min, or history of serious renal disease
10. Urine dipstick protein ≥ 2+
11. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
12. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
13. Any laboratory value or uncontrolled medical conditions that, in the opinion of investigators, would interfere with the study conditions or increase risk to the participant
14. > Grade I abnormalities in screening laboratory tests (Complete Blood Count, Comprehensive Metabolic Panel, Lipase, Phosphorus) per Division of AIDS (DAIDS) Grading Table
15. Contraindicated concomitant medications based upon product information or that, in the opinion of the investigators, would interact with the study medications or increase risk to participant such as: investigational agents (within 30 days of enrollment), aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir (>800mg acyclovir or > 500mg valacyclovir for > 7 days), cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir.
16. Current participation in other interventional research studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Truvada; Naked form Truvada (drug)	Drug: TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET [TRUVADA]; Other Names: Truvada
Experimental: PSS-Truvada; Proteus Sensor System (PSS) (device) encapsulated Truvada (drug)	Drug: TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET [TRUVADA]; Other Names: Truvada; Device: Proteus Sensor System; Other Names: PSS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	Tenofovir and emtricitabine concentration max (Cmax) following FTC/TDF in the overencapsulated versus non-encapsulated form. Drug concentrations will be assayed with validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methodology.	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Area Under the Concentration-time Curve (AUC)	Tenofovir and emtricitabine area under the concentration-time curve (AUC) following FTC/TDF in the overencapsulated versus non-encapsulated form. Drug concentrations will be assayed with validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methodology.	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Peter Anderson, PharmD, University of Colorado, Denver

Publications and helpful links

General Publications

• Ibrahim ME, Brooks KM, Castillo-Mancilla JR, McHugh C, Morrow M, Brothers J, MaWhinney S, Hosek S, Huhn G, Anderson PL. Short Communication: Bioequivalence of Tenofovir and Emtricitabine After Coencapsulation with the Proteus Ingestible Sensor. AIDS Res Hum Retroviruses. 2018 Oct;34(10):835-837. doi: 10.1089/AID.2018.0081. Epub 2018 Sep 5.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: November 8, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: 16-1478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO