The Cellular Pharmacology of F-TAF in Dried Blood Spots

NCT ID: NCT02962739

Last Updated: 2021-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-05-22

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

33%/67% dosing

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).

Group Type: ACTIVE_COMPARATOR

emtricitabine 200 mg/tenofovir alafenamide 25mg

Intervention Type: DRUG

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

33%/100% dosing

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.

Group Type: ACTIVE_COMPARATOR

emtricitabine 200 mg/tenofovir alafenamide 25mg

Intervention Type: DRUG

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

67%/33% dosing

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).

Group Type: ACTIVE_COMPARATOR

emtricitabine 200 mg/tenofovir alafenamide 25mg

Intervention Type: DRUG

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

67%/100% dosing

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.

Group Type: ACTIVE_COMPARATOR

emtricitabine 200 mg/tenofovir alafenamide 25mg

Intervention Type: DRUG

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

100%/33% dosing

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.

Group Type: ACTIVE_COMPARATOR

emtricitabine 200 mg/tenofovir alafenamide 25mg

Intervention Type: DRUG

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

100%/67% dosing

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.

Group Type: ACTIVE_COMPARATOR

emtricitabine 200 mg/tenofovir alafenamide 25mg

Intervention Type: DRUG

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

Interventions

emtricitabine 200 mg/tenofovir alafenamide 25mg

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

Intervention Type: DRUG

Other Intervention Names

Descovy

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Ability to comply with study procedures, including directly observed dosing visits and availability and use of video streaming technology.

Exclusion Criteria

1. Inability to give informed consent

2. Pregnancy or plan to become pregnant in the next 12 months or unwillingness to use birth control

3. Current 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 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

5. 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,
• vomiting,
• myalgia, .
• diarrhea,
• pharyngitis,
• rash,
• night sweats, and
• adenopathy (cervical or inguinal)

6. Positive Hepatitis B Virus (HBV) surface antigen test at screening

7. Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements.

8. Glomerular Filtration Rate (GFR) estimate < 60 ml/min (MDRD equation).

9. Urine dipstick protein ≥ 2+

10. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal

11. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.

12. Symptomatic hemoglobinopathies or active hemolysis.

13. History of pathological, non-traumatic bone fractures

14. Any laboratory value or uncontrolled medical conditions that, in the opinion of the investigators, would interfere with the study conditions such as, heart disease and/or cancer.

15. Prohibited concomitant medications are:

• 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, respectively.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Anderson, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado- Anschutz Campus

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 32539288 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16-0972

Identifier Type: -

Identifier Source: org_study_id