NCT03864406

Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Health Volunteers

Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Healthy Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: National Institutes of Health Clinical Center (CC) · NIH
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Background: Rivaroxaban and apixaban are blood thinners. People with HIV may need to take them to treat or prevent blood clots. The anti-HIV drug darunavir (DRV) can increase the amount of these blood thinners in the body. This can cause bleeding or other health problems. The drug cobicistat (COBI) is used to help anti-HIV drugs work better. Researchers want to give healthy people DRV combined with COBI to learn how it affects rivaroxaban or apixaban blood levels. Objective: To test blood levels of rivaroxaban or apixaban when taken with COBI and DRV/COBI. Eligibility: Healthy volunteers ages 18-65 Design: Participants will be screened with: Medical history Physical exam Fasting blood and urine tests. (Urine tests will be performed in females of child-bearing potential only) Participants will have 8 visits; 3 are long (about 10-12 hours) and 5 are about 1 hour. They include: Baseline and final visits: Fasting blood and urine tests Day 1 visit (long day): Fasting blood and urine tests Catheter placement: A needle will insert a small tube into the participant's arm vein. Blood will be drawn up to 10 times. Dose of rivaroxaban or apixaban Day 2 visit (short day): Fasting blood tests Dose of COBI Participants will receive a bottle containing COBI tablets to take at home. Day 7 (long day): Fasting blood and urine tests Catheter placement: A needle will insert a small tube into the participant's arm vein. Blood will be drawn up to 10 times. Dose of rivaroxaban or apixaban Dose of COBI Day 8 (short day): Fasting blood tests Dose of DRV/COBI Participants will receive a bottle containing DRV/COBI tablets to take at home. Day 13 (long day): Fasting blood and urine tests Catheter placement: A needle will insert a small tube into the participant s arm vein. Blood will be drawn up to 10 times. Dose of rivaroxaban or apixaban Dose of DRV/COBI Day 14 (short day): Fasting blood tests Participants will take COBI tablets daily at home on days 3-6, and DRV/COBI on days 9 -12 during the study. They will record doses and side effects. During the study, participants cannot: Take most medications. Drink alcohol, smoke, or vape Engage in activities such as contact and extreme sports

Detailed description

Rivaroxaban is a direct oral anticoagulant (DOAC) used for the prevention and treatment of various thromboembolic disorders. Predictable pharmacokinetic (PK) and pharmacodynamic (PD) properties, coupled with a few drug drug and food-drug interactions, distinguishes DOACs from a traditionally used anticoagulant, warfarin, allowing fixed dosing without routine coagulation monitoring. Patients with human immunodeficiency virus (HIV) are living as long as their HIV negative counterparts due to safe and efficacious antiretroviral therapy (ART). Persons with HIV are at higher risk for thromboembolic events and DOACs are a feasible option for anticoagulation in this population. However, there is a lack of drug interaction and safety data currently on the co-administration cobicistat (COBI)-boosted antiretroviral (ARV) regimens with rivaroxaban. Rivaroxaban is metabolized by cytochrome P450 isozyme (CYP) 3A4 and its absorption is modulated by permeability glycoprotein (P-gp), both of which are inhibited by the PK booster COBI. It is therefore possible that plasma concentrations of rivaroxaban may be significantly increased when co-administered together with COBI. This is of clinical concern as increased anticoagulant exposure may result in bleeding without the security of routine clinical monitoring. The purpose of this study is to determine the effects of steady state concentrations of COBI and darunavir (DRV)/COBI on the PK and PD of single oral doses of rivaroxaban.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	Cobicistat	Each tablet of Tybost contains 150 mg of cobicistat.
DRUG	Darunavir/Cobicistat	Each tablet of Prezcobix contains 800 mg of darunavir and 150 mg of cobicistat.
DRUG	Rivaroxaban	Each tablet of Xarelto contains 10 mg of rivaroxaban.

Timeline

• Start date: 2019-06-04
• Primary completion: 2022-12-10
• Completion: 2022-12-10
• First posted: 2019-03-06
• Last updated: 2023-12-01
• Results posted: 2023-12-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study