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The Cellular Pharmacology of F-TAF in Dried Blood Spots (TAF-DBS)

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ClinicalTrials.gov Identifier: NCT02962739
Recruitment Status : Completed
First Posted : November 11, 2016
Results First Posted : January 25, 2021
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE November 8, 2016
First Posted Date  ICMJE November 11, 2016
Results First Submitted Date  ICMJE February 6, 2020
Results First Posted Date  ICMJE January 25, 2021
Last Update Posted Date January 25, 2021
Actual Study Start Date  ICMJE March 2016
Actual Primary Completion Date May 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2021)
Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy [ Time Frame: Assessed weekly for 9 months ]
Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) respective to dosing regimens of 33%, 67%, 100% of daily dosing.
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
  • Change in Tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) concentrations [ Time Frame: Weekly for 9 months ]
  • Model Prediction for Adherence [ Time Frame: Weekly for 9 months ]
    Establish a model to predict adherence rate to F-TAF by level of TFV-DP in DBS.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
  • Change in Dose proportionally for TFV-DP in Peripheral Blood Mononuclear Cells (PBMC) and Tenofovir (TFV)/ Emtricitabine (FTC) in hair. [ Time Frame: Every week for 9 months ]
  • Change in Dose proportionally for Tenofovir (TFV)/ Emtricitabine (FTC) in hair. [ Time Frame: Every 3 weeks for 9 months ]
  • Change in Before therapy versus on therapy and at steady-state. [ Time Frame: Weekly for 9 months ]
    Comparison of relevant endogenous molecules such as nucleo(s)tides before therapy versus on therapy and at steady-state.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Cellular Pharmacology of F-TAF in Dried Blood Spots
Official Title  ICMJE The Cellular Pharmacology of F-TAF in Dried Blood Spots
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy Volunteers
Intervention  ICMJE Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg
Other Name: Descovy
Study Arms  ICMJE
  • Active Comparator: 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).
    Intervention: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
  • Active Comparator: 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.
    Intervention: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
  • Active Comparator: 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).
    Intervention: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
  • Active Comparator: 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.
    Intervention: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
  • Active Comparator: 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.
    Intervention: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
  • Active Comparator: 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.
    Intervention: Drug: emtricitabine 200 mg/tenofovir alafenamide 25mg
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2021)
38
Original Estimated Enrollment  ICMJE
 (submitted: November 9, 2016)
72
Actual Study Completion Date  ICMJE May 22, 2019
Actual Primary Completion Date May 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 59 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02962739
Other Study ID Numbers  ICMJE 16-0972
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Anderson, PharmD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP