Healthy Volunteers
Conditions
Keywords
healthy volunteers
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.
Interventions
DRUGemtricitabine 200 mg/tenofovir alafenamide 25mg
1 tablet of Descovy contains emtricitabine 200 mg/tenofovir alafenamide 25mg
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Dosing Regimens Baseline characteristics for all 35 subjects analyzed. Baseline characteristics not stratified based on dosing regimen. Arms were combined to be consistent with protocol subject randomization. Subjects were randomized to one of six arms. Combined arms best categorize the study, population, and data. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Dosing Regimens |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Race/Ethnicity, Customized African American | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 24 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 2 / 38 |
Outcome results
Primary
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.
Time frame: Assessed weekly for 9 months
Population: 34 participants received 2 of 3 dosing regimens and 1 participant only completed through week 8 of the second regimen, resulting in a total of 69 observations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DOT 33% | Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy | 657 fmol/punch | Standard Deviation 186 |
| DOT 67% | Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy | 1451 fmol/punch | Standard Deviation 501 |
| DOT 100% | Steady State Concentrations of TFV-DP for Different Dosing Patterns of Descovy | 2381 fmol/punch | Standard Deviation 601 |