The Cellular Pharmacology of F-TAF in Dried Blood Spots

NCT02962739 | Completed Phase 1 Results

• 1 other identifier: 16-0972
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Adherence to daily dosing is very important for how well Emtricitabine/Tenofovir Alafenamide (F/TAF) works for treatment of chronic human immunodeficiency virus (HIV), or prevention of HIV acquisition. Methods to measure medication adherence to Tenofovir disoproxil fumarate (tenofovir DF, TDF), a similar but different prodrug of tenofovir, have been developed but cannot be extrapolated to F-TAF. By measuring F-TAF (the drug) and metabolites in the blood cells and dried blood spots, the study plans to see if these results predict adherence to taking the drug. The goal of this study is to vary the amount of F-TAF dosing and see if the drug levels in dried blood spots (DBS) change in a predictable way. This study will mimic different levels of adherence (33%, 67%, and 100% of daily dosing) using directly observed therapy (DOT) to establish the relationship between F-TAF in dried blood spots and adherence. Investigators will also measure drug in hair clippings to see if hair or DBS are a better predictor of adherence.

Conditions

Healthy Volunteers

Keywords

healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy

  Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) respective to dosing regimens of 33%, 67%, 100% of daily dosing.

  Assessed weekly for 9 months

Study Arms (6)

33%/67% dosing

ACTIVE COMPARATOR

The 33% and 67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks; 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks).

Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

33%/100% dosing

ACTIVE COMPARATOR

The 33% dosing regimens will use skipped doses spaced by days (i.e. 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks). 100% will dose daily for 12 weeks, no skipped doses.

Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

67%/33% dosing

ACTIVE COMPARATOR

The 33% and 67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks; 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks).

Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

67%/100% dosing

ACTIVE COMPARATOR

67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks. 100% will dose daily for 12 weeks, no skipped doses.

Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

100%/33% dosing

ACTIVE COMPARATOR

The 33% dosing regimens will use skipped doses spaced by days (i.e. 33% dosing is a daily dose followed by two skipped days, repeated for 12 weeks). 100% will dose daily for 12 weeks, no skipped doses.

Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

100%/67% dosing

ACTIVE COMPARATOR

67% dosing regimens will use skipped doses spaced by days (i.e. 67% is two daily doses followed by skipping a day, repeated for 12 weeks. 100% will dose daily for 12 weeks, no skipped doses.

Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg

Interventions

emtricitabine 200 mg/tenofovir alafenamide 25mg DRUG

1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg

Also known as: Descovy

100%/33% dosing; 100%/67% dosing; 33%/100% dosing; 33%/67% dosing; 67%/100% dosing; 67%/33% dosing

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ambulatory 18-59 year old adults. Enrollment will proceed without the need to meet specific race/gender targets, but balanced gender and African-Americans and Latino representation will be sought.
• Ability to comply with study procedures, including directly observed dosing visits and availability and use of video streaming technology.

You may not qualify if:

• Inability to give informed consent
• Pregnancy or plan to become pregnant in the next 12 months or unwillingness to use birth control
• Current 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 condomless intercourse with HIVinfected 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 screening 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,

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado- Anschutz Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Yager J, Castillo-Mancilla J, Ibrahim ME, Brooks KM, McHugh C, Morrow M, McCallister S, Bushman LR, MaWhinney S, Kiser JJ, Anderson PL. Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots Following Tenofovir Alafenamide: The TAF-DBS Study. J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):323-330. doi: 10.1097/QAI.0000000000002354.

  PMID: 32539288 RESULT

MeSH Terms

Interventions

Emtricitabine; tenofovir alafenamide; emtricitabine tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

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

peter.anderson@cuanschutz.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: phase 1
• 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 11, 2016
• Study Start: March 1, 2016
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: January 25, 2021
• Results First Posted: January 25, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)