Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Health Volunteers
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Cobicistat; Darunavir/Cobicistat; Rivaroxaban
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Each tablet of Tybost contains 150 mg of cobicistat.; Each tablet of Prezcobix contains 800 mg of darunavir and 150 mg of cobicistat.; Each tablet of Xarelto contains 10 mg of rivaroxaban.
Other intervention name(s): Tybost; Prezcobix; Xarelto
Intervention MeSH terms: Darunavir; Cobicistat; Cobicistat mixture with darunavir; Rivaroxaban
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Antiretroviral Therapy; Human Immunodeficiency Disease; Drug-Drug Interactions; Thrombosis; Bleeding