Bioequivalence of Tenofovir and Emtricitabine Following Overencapsulation

NCT02968576 | Completed Results DMC

• 1 other identifier: 16-1478
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Volunteers; Pharmacokinetics

Keywords

healthy volunteers; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Truvada

ACTIVE COMPARATOR

Naked form Truvada (drug)

Drug: TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET [TRUVADA]

PSS-Truvada

EXPERIMENTAL

Proteus Sensor System (PSS) (device) encapsulated Truvada (drug)

Drug: TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET [TRUVADA]; Device: Proteus Sensor System

Interventions

TENOFOVIR DISOPROXIL FUMARATE 300 Mg / EMTRICITABINE 200 Mg ORAL TABLET [TRUVADA] DRUG

Also known as: Truvada

PSS-Truvada; Truvada

Proteus Sensor System DEVICE

Also known as: PSS

PSS-Truvada

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Inability to give informed consent
• Pregnancy or planning to become pregnant within 3 months of study completion
• Currently breastfeeding
• 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)
• 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)
• Positive hepatitis B virus (HBV) surface antigen test.
• Uncontrolled or symptomatic bone disease or history of non-traumatic bone fractures
• Active psychiatric illness or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements
• Creatinine clearance \< 60 ml/min, or history of serious renal disease
• Urine dipstick protein ≥ 2+
• Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
• Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
• 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
• \> Grade I abnormalities in screening laboratory tests (Complete Blood Count, Comprehensive Metabolic Panel, Lipase, Phosphorus) per Division of AIDS (DAIDS) Grading Table
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Related Publications (1)

• 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.

  PMID: 30047286 BACKGROUND

MeSH Terms

Interventions

Tenofovir; Emtricitabine; Tablets; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dosage Forms; Pharmaceutical Preparations; Drug Combinations

Results Point of Contact

• Title: Dr. Peter Anderson
• Organization: University of Colorado | Skaggs School of Pharmacy and Pharmaceutical Sciences

peter.anderson@ucdenver.edu

3037246128

Study Officials

• Peter Anderson, PharmD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2016
• First Posted: November 18, 2016
• Study Start: December 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: March 6, 2020
• Results First Posted: May 14, 2019

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share