Healthy VolunteersPhase 1NCT03864406
Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Health Volunteers
A Phase 1 study testing Cobicistat, Darunavir/Cobicistat and Rivaroxaban in people with Healthy Volunteers, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Cobicistat, Darunavir/Cobicistat and Rivaroxaban
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jun 2019to 10 Dec 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject will be considered eligible for this study only if all of the following criteria are met:
- Adults between the ages of 18 to 65 years.
- Body mass index between 18 to 30 kg/M(2).
- Judged to be healthy based on medical history, physical examination, vital signs and clinical laboratory tests (liver function tests (LFTs: alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin less than or equal to upper limit of normal (ULN) (with the exception of participants with Gilbert's syndrome), albumin within normal limits (WNL)], eGFR > 90 mL/min/1.73 m(2), PLT>150,000/microL, hemoglobin (Hgb) greater than or equal to 12 g/dL, activated partial thromboplastin time (aPTT) less than or equal to ULN, partial thromboplastin time (PTT) less than or equal to ULN, international normalized ratio (INR) less than or equal to ULN.
- Subject agrees to storage of specimens for future research.
- Negative serum or urine pregnancy test for females of child-bearing potential.
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- For female subjects, willing to avoid pregnancy by (a) practicing abstinence or (b) using effective non-hormonal and/or barrier methods of birth control, as well as avoid breast feeding or providing breast milk to infant during the study period. (baseline visit up to end of study day 20 plus minus 3)
- Willing to avoid engaging in activities such as contact sports, including extreme sports, that may increase the risk of bleeding through body injury or bruising, during the study period (baseline visit up to end of study day 20 plus minus 3)
- Willingness to forgo drinking alcohol during the study period (baseline visit up to end of study day 20 plus minus 3)
- Able to provide consent.
Who cannot join
- A subject will be ineligible for this study if one, or more, of the following criteria are met:
- HIV infection, as determined by standard serologic or virologic assays for HIV infection.
- Laboratory evidence of active or chronic hepatitis A, B or C infection.
- History or presence of any of the following:
- any major medical conditions that requires daily frequent medication or potentially impairs medication absorption, metabolism and elimination
- any other condition that may interfere with the interpretation of the study results, or not be in the best interest of the subject in the opinion of the Investigator.
Show all 25Show fewer
- 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/medications.
- History or presence of the following:
- bleeding/hematologic disorders (e.g., anemia, hemophilia, etc.),
- serious/major bleeding event (intracranial, gastrointestinal (GI), as assessed by subject interview), or
- current increased risk of bleeding
- for female subjects, menorrhagia
- Planned invasive or surgical procedure within (prior to or following) 28 days of study participation.
- Therapy with any prescription, over-the-counter, 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 (<14 days) with prescription, vaccines or over-the-counter medications will be reviewed by investigators on a case-by-case basis for potential drug interactions.
- Inability to obtain venous access for sample collection.
- Inability to swallow whole capsules and/or tablets.
- Pregnant female.
- Breastfeeding female.
- The presence of persistent diarrhea or malabsorption that could interfere with the subject's ability to absorb drugs.
- Illicit drug or alcohol use
- Use of nicotine-containing tobacco products, including cigarettes, vaping and chewing tobacco.
- Known hypersensitivity to rivaroxaban, apixaban, COBI or DRV.
- History of documented hypersensitivity to sulfa allergy.
- Organ transplant recipient.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Healthy Volunteers
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.
Read more
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
Read the 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
- Being tested
- Cobicistat, Darunavir/Cobicistat, Rivaroxaban
- Keywords
- Antiretroviral Therapy, Human Immunodeficiency Disease, Drug-Drug Interactions, Thrombosis, Bleeding
- Medical subject headings
- Thrombosis, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobicistatDrug
Also called Tybost
Each tablet of Tybost contains 150 mg of cobicistat.
Darunavir/CobicistatDrug
Also called Prezcobix
Each tablet of Prezcobix contains 800 mg of darunavir and 150 mg of cobicistat.
RivaroxabanDrug
Also called Xarelto
Each tablet of Xarelto contains 10 mg of rivaroxaban.
| Study group | Role | What they receive |
|---|---|---|
| Pharmacokinetic study in healthy volunteers | Experimental | Healthy participants received a single dose of rivaroxaban 10 mg orally on day 1 (phase 1) followed by cobicistat 150 mg once daily from days 2 - 7 and a single dose of rivaroxaban 10 mg on day 7 (phase 2). Participants received darunavir /cobicistat 800/150 mg once daily from days 8 - 13 followed by a single dose of rivaroxaban 10mg on day 13 (phase 3). Serial blood sampling was done on days 1, 7, and 13. Receives: Drug: Cobicistat; Drug: Darunavir/Cobicistat; Drug: Rivaroxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Concentration Versus Time Curve (AUC0-∞) for Rivaroxaban
Area under the concentration versus time curve from 0 to infinity (AUC0-∞) following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 to measure the total drug exposure was analyzed by the linear up/log down trapezoidal rule using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA).
Measured: Total drug exposure at time point zero to infinity on days 1, 7, & 13
Area Under the Concentration Versus Time Curve (AUC0-24hr) for Rivaroxaban
Area under the concentration versus time curve from (AUC0-24hr) following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 to measure total drug exposure was analyzed by the linear up/log down trapezoidal rule using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA).
Measured: 0 to 24 hours postdose on days 1, 7, and 13
Maximum Total Plasma Concentration (Cmax) for Rivaroxaban
Maximum total plasma concentration (Cmax) following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). Cmax for rivaroxaban was obtained directly by visual inspection of the plasma concentration versus time over 24 hours postdose.
Measured: Up to 24 hours postdose on days 1, 7, and 13
Time to Maximum Plasma Concentration (Tmax) for Rivaroxaban
Time to maximum plasma concentration for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). Tmax for rivaroxaban was obtained directly by visual inspection of the plasma concentration versus time over 24 hours postdose.
Measured: Up to 24 hours postdose on days 1, 7, and 13
Terminal Elimination Half-life (t½) for Rivaroxaban
Terminal elimination half-life (t½) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). The apparent elimination rate constant (λZ) was determined by calculating the absolute value of the slope of the log-linear regression of at least 3 points of the plasma concentration-time plot. The t½ was calculated as 0.693/apparent elimination rate constant (λZ).
Measured: Up to 24 hours postdose on days 1, 7, and 13
Apparent Oral Clearance (CL/F) for Rivaroxaban
Apparent oral clearance (CL/F) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). CL/F was calculated as 10 mg ÷ AUC0-tau for rivaroxaban.
Measured: Up to 24 hours postdose on days 1, 7, and 13
Apparent Volume of Distribution (V/F) for Rivaroxaban
Apparent volume of distribution (V/F) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA).
Measured: Up to 24 hours postdose on days 1, 7, and 13
Minimum Total Plasma Concentration (Cmin) for Rivaroxaban
Minimum total plasma concentration (Cmin) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). Cmin for rivaroxaban was obtained directly by visual inspection of the plasma concentration versus times over 24 hours postdose.
Measured: Up to 24 hours postdose on days 1, 7, and 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2019
- Study start4 Jun 2019
- Primary completion10 Dec 2022
- Study completion10 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Colleen M Hadigan, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03864406
- Sponsor's protocol ID
- 190063
- Other IDs
- 19-CC-0063
- Status last verified
- Apr 2023
- First submitted
- 5 Mar 2019
- Last updated
- 1 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not reported or shared. The study team are the only individuals who have access to individual participant data. All data will be analyzed and reported in aggregate.
Publications
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.
PubMed 23305158Kumar 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.
PubMed 28848011Frost 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.
PubMed 23451769
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Steady State Cobicistat and Darunavir/Cobicistat on the Pharmacokinetics and Pharmacodynamics of Oral Anticoagulants (Rivaroxaban, Apixaban) in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03864406
- Acronym / sponsor ID
- 190063
- Conditions
- Healthy Volunteers
- Keywords
- Antiretroviral Therapy, Human Immunodeficiency Disease, Drug-Drug Interactions, Thrombosis, Bleeding
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 4 Jun 2019 (actual)
- Primary completion
- 10 Dec 2022 (actual)
- Study completion
- 10 Dec 2022 (actual)
- First posted
- 6 Mar 2019 (actual)
- Results
- Posted 1 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pharmacokinetic study in healthy volunteers | Experimental | Drug: Cobicistat, Drug: Darunavir/Cobicistat, Drug: RivaroxabanHealthy participants received a single dose of rivaroxaban 10 mg orally on day 1 (phase 1) followed by cobicistat 150 mg once daily from days 2 - 7 and a single dose of rivaroxaban 10 mg on day 7 (phase 2). Participants received darunavir /cobicistat 800/150 mg once daily from days 8 - 13 followed by a single dose of rivaroxaban 10mg on day 13 (phase 3). Serial blood sampling was done on days 1, 7, and 13. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- A subject will be considered eligible for this study only if all of the following criteria are met:
- Adults between the ages of 18 to 65 years.
- Body mass index between 18 to 30 kg/M(2).
- Judged to be healthy based on medical history, physical examination, vital signs and clinical laboratory tests (liver function tests (LFTs: alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin less than or equal to upper limit of normal (ULN) (with the exception of participants with Gilbert's syndrome), albumin within normal limits (WNL)], eGFR > 90 mL/min/1.73 m(2), PLT>150,000/microL, hemoglobin (Hgb) greater than or equal to 12 g/dL, activated partial thromboplastin time (aPTT) less than or equal to ULN, partial thromboplastin time (PTT) less than or equal to ULN, international normalized ratio (INR) less than or equal to ULN.
- Subject agrees to storage of specimens for future research.
Key exclusion criteria (25 listed)
- A subject will be ineligible for this study if one, or more, of the following criteria are met:
- HIV infection, as determined by standard serologic or virologic assays for HIV infection.
- Laboratory evidence of active or chronic hepatitis A, B or C infection.
- History or presence of any of the following:
- 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/medications.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobicistatAlso: TybostEach tablet of Tybost contains 150 mg of cobicistat. | Drug | Pharmacokinetic study in healthy volunteers |
| Darunavir/CobicistatAlso: PrezcobixEach tablet of Prezcobix contains 800 mg of darunavir and 150 mg of cobicistat. | Drug | Pharmacokinetic study in healthy volunteers |
| RivaroxabanAlso: XareltoEach tablet of Xarelto contains 10 mg of rivaroxaban. | Drug | Pharmacokinetic study in healthy volunteers |
Primary outcome
Area Under the Concentration Versus Time Curve (AUC0-∞) for Rivaroxaban
Time frame: Total drug exposure at time point zero to infinity on days 1, 7, & 13
Area under the concentration versus time curve from 0 to infinity (AUC0-∞) following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 to measure the total drug exposure was analyzed by the linear up/log down trapezoidal rule using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA).
Area Under the Concentration Versus Time Curve (AUC0-24hr) for Rivaroxaban
Time frame: 0 to 24 hours postdose on days 1, 7, and 13
Area under the concentration versus time curve from (AUC0-24hr) following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 to measure total drug exposure was analyzed by the linear up/log down trapezoidal rule using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA).
Maximum Total Plasma Concentration (Cmax) for Rivaroxaban
Time frame: Up to 24 hours postdose on days 1, 7, and 13
Maximum total plasma concentration (Cmax) following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). Cmax for rivaroxaban was obtained directly by visual inspection of the plasma concentration versus time over 24 hours postdose.
Time to Maximum Plasma Concentration (Tmax) for Rivaroxaban
Time frame: Up to 24 hours postdose on days 1, 7, and 13
Time to maximum plasma concentration for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). Tmax for rivaroxaban was obtained directly by visual inspection of the plasma concentration versus time over 24 hours postdose.
Terminal Elimination Half-life (t½) for Rivaroxaban
Time frame: Up to 24 hours postdose on days 1, 7, and 13
Terminal elimination half-life (t½) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). The apparent elimination rate constant (λZ) was determined by calculating the absolute value of the slope of the log-linear regression of at least 3 points of the plasma concentration-time plot. The t½ was calculated as 0.693/apparent elimination rate constant (λZ).
Apparent Oral Clearance (CL/F) for Rivaroxaban
Time frame: Up to 24 hours postdose on days 1, 7, and 13
Apparent oral clearance (CL/F) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). CL/F was calculated as 10 mg ÷ AUC0-tau for rivaroxaban.
Apparent Volume of Distribution (V/F) for Rivaroxaban
Time frame: Up to 24 hours postdose on days 1, 7, and 13
Apparent volume of distribution (V/F) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA).
Minimum Total Plasma Concentration (Cmin) for Rivaroxaban
Time frame: Up to 24 hours postdose on days 1, 7, and 13
Minimum total plasma concentration (Cmin) for Rivaroxaban following a single dose of rivaroxaban 10 mg orally on days 1, 7, and 13 was analyzed using noncompartmental methods with Phoenix WinNonlin® (version 8.0; Pharsight Corporation, Mountain View, CA). Cmin for rivaroxaban was obtained directly by visual inspection of the plasma concentration versus times over 24 hours postdose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23305158Mueck 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: PubMed 28848011Kumar 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: PubMed 23451769Frost 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. Individual participant data will not reported or shared. The study team are the only individuals who have access to individual participant data. All data will be analyzed and reported in aggregate.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colleen M Hadigan, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cobicistat, Darunavir/Cobicistat and Rivaroxaban in people with Healthy Volunteers, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Concentration Versus Time Curve (AUC0-∞) for Rivaroxaban (time frame: Total drug exposure at time point zero to infinity on days 1, 7, & 13). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03864406, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2023.