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

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

Timeline

Start

2019-06-04

Primary completion

2022-12-10

Completion

2022-12-10

Publications

• Background Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013 Sep;76(3):455-66. doi: 10.1111/bcp.12075.
• Background Kumar P, Gordon LA, Brooks KM, George JM, Kellogg A, McManus M, Alfaro RM, Nghiem K, Lozier J, Hadigan C, Penzak SR. Differential Influence of the Antiretroviral Pharmacokinetic Enhancers Ritonavir and Cobicistat on Intestinal P-Glycoprotein Transport and the Pharmacokinetic/Pharmacodynamic Disposition of Dabigatran. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01201-17. doi: 10.1128/AAC.01201-17. Print 2017 Nov.
• Background Frost C, Nepal S, Wang J, Schuster A, Byon W, Boyd RA, Yu Z, Shenker A, Barrett YC, Mosqueda-Garcia R, Lacreta F. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Br J Clin Pharmacol. 2013 Nov;76(5):776-86. doi: 10.1111/bcp.12106.

Drugs

Indications

No indication recorded.