Phase 1
Completed N=28
Impact of Weekly Administration of Rifapentine and Isoniazid on Steady State Pharmacokinetics of Tenofovir Alafenamide in Healthy Volunteers (YODA)
Healthy Volunteers
Source: ClinicalTrials.gov NCT03510468 ↗
Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Oct 2023
Primary outcomePrimary: Plasma Area Under the Curve (AUC) for Tenofovir Alafenamide (TAF) During the Dosing Interval of 0 to 24 Hours (AUC0-24hr) — 295.5; 472.1; 248.1 hr*ng/ml
Summary
Background:
Human immunodeficiency virus (HIV) is treated with antiretroviral drugs. Many people with HIV also have the lung infection tuberculosis (TB). Most TB treatments are complicated. A simpler treatment of two TB drugs can be taken once a week. Researchers want to study how the HIV and TB drugs affect each other so people who take both can be treated safely.
Objective:
To study if rifapentine and isoniazid affect blood levels of the common antiretroviral TAF.
Eligibility:
Healthy adults ages 18-65 without HIV, TB, or hepatitis
Design:
Participants will fast before the screening visit. They will have a medical history, physical exam, and blood tests. Women may have a pregnancy test.
During the study, participants must:
Use effective birth control
Not take most medicine
Not drink alcohol
At the baseline visit, participants will repeat screening tests and get TAF tablets.
Participants will take TAF once a day for 31 days. They will keep track of doses and side effects.
Over 32 days, participants will have 4 long visits and 4 short.
At all visits, participants will:
Fast the night before
Get food
Take that day's TAF
Review their TAF supply
Have pregnancy and blood tests
Report side effects
At 3 visits, participants will also take the 2 TB drugs and vitamin B6.
At 3 long visits, participants will also have blood collected 8 times over 8 hours by plastic tube in an arm vein.
Around Day 46, participants will fast and have blood and pregnancy tests. Two weeks later, they will get a call to see how they are feeling.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Plasma Area Under the Curve (AUC) for Tenofovir Alafenamide (TAF) During the Dosing Interval of 0 to 24 Hours (AUC0-24hr) |
295.5; 472.1; 248.1 | — |
| PRIMARY Plasma Area Under the Curve (AUC) for Tenofovir (TFV) During the Dosing Interval of 0 to 24 Hours (AUC0-24hr) |
262.2; 265.3; 230.8 | — |
| PRIMARY Maximum Total Plasma Concentration (Cmax) for Tenofovir Alafenamide (TAF) |
208.9; 335.2; 179.1 | — |
| PRIMARY Maximum Total Plasma Concentration (Cmax) for Tenofovir (TFV) |
16.5; 16.5; 13.8 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) for Tenofovir Alafenamide (TAF) |
0.5; 0.57; 0.5 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) for Tenofovir (TFV) |
4; 4; 4 | — |
| PRIMARY Terminal Half-life (t½) of Tenofovir (TFV) |
39.8; 42.6; 33.5 | — |
| PRIMARY Apparent Oral Clearance (CL/F) of Tenofovir Alafenamide (TAF) |
84.6; 52.9; 100.8 | — |
| PRIMARY Minimum Total Plasma Concentration (Cmin) for Tenofovir Alafenamide (TAF) |
2.4; 2.9; 2 | — |
| PRIMARY Minimum Total Plasma Concentration (Cmin) for Tenofovir (TFV) |
9.1; 7.2; 8.7 | — |
| SECONDARY Plasma Area Under the Curve (AUC) for Intracellular Tenofovir Di-phosphate During the Dosing Interval of 0 to 24 Hours (AUC0-24hr) |
NA; NA; NA | — |
| SECONDARY Terminal Half-life (t½) of Intracellular Tenofovir-diphosphate |
NA; NA; NA | — |
Eligibility Criteria
- PARTICIPANT INCLUSION CRITERIA:
Individuals must meet all of the following criteria to be eligible for study participation:
- Ages 18-65 years.
- Weight greater than or equal to 45 kg and less than or equal to 120 kg OR body mass index greater than or equal to 18.0 and 150,000/microL, hemoglobin (Hgb) > 13 g/dL (males); greater than or equal to 12g/dL (females), C-reactive protein (CRP) less than or equal to ULN, creatine kinase (CK) less than or equal to 2x ULN, fasting total cholesterol ULN).
- Respiratory disease that is uncontrolled or requires daily treatment with medication (eg, asthma or chronic obstructive pulmonary disease).
- Cardiovascular disease (eg, hypertension [systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg], heart failure, or arrhythmia).
- Metabolic disorders (eg, diabetes mellitus).
- Hematologic or bleeding disorders (eg, anemia, hemophilia, serious/major bleeding events, menorrhagia [female participants]).
- Immunologic disorders.
- Hormonal or endocrine disorders.
- Psychiatric illness that would interfere with their ability to comply with study procedures or that requires daily treatment with medication.
- Seizure disorder, with the exception of childhood febrile seizures.
- Any current or history of malignancy, with the exception of cutaneous basal cell carcinoma,non-invasive squamous cell carcinoma, or any other malignancies not requiring systemic
therapy.
- Current or history of osteopenia and osteoporosis.
- Current participation in an ongoing investigational drug protocol or use of any investigational drug within 30 days (based on last dose received) prior to receipt of any study drugs.
- Therapy with any prescription, over-the-counter (OTC), herbal, or holistic medications, including hormonal contraceptives by any route, within 5 half-lives of the agent prior to receipt of any study medications will not be permitted with the following exception: Intermittent or short-course therapy ( 240 mg/dL or fasting triglycerides > 240 mg/dL at screening.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Data sourced from ClinicalTrials.gov (NCT03510468). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.