A Prospective Multi-dose Study of Apixaban in Subjects With Nephrotic Syndrome

September 25, 2023 updated by: University of North Carolina, Chapel Hill
This phase I study is a single arm, multi-dose study that will evaluate steady-state apixaban pharmacokinetics (PK) and pharmacodynamics (PD) in subjects with Nephrotic Syndrome (NS) vs healthy control subjects. This study will enroll 20 subjects diagnosed with NS and 10 healthy control subjects. Comparing differences in steady-state apixaban PK/PD parameters between subjects with NS and healthy volunteers will be essential to identifying a safe and effective apixaban dose and dose administration schedule for future randomized controlled trials (RCTs).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27517
        • University of North Carolina at Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Study Subjects

  • 18-79 years of age
  • Confirmed diagnosis of NS, with at least one of the following (confirmed within 1 month prior to scheduled Day 1 Study Visit):
  • Nephrotic-range proteinuria, defined as >3.0 g/24 hours
  • UPC (ratio of protein to creatinine in random spot urine sample), defined as >3.0
  • Hypoalbuminemia, defined as <3.0 g/dL

Control Subjects

  • 18-79 years of age
  • Normal albumin levels (>3.0 mg/dL)
  • No history of chronic kidney disease

Exclusion Criteria:

  • Age <18 or ≥80 years old
  • Serum Creatinine (SCr) ≥1.5 AND weight ≤60kg (these subjects would receive a reduced apixaban dose, per drug labeling)
  • Weight >120 kg OR body mass index (BMI) ≥40 kg/m^2
  • Estimated Glomerular Filtration Rate (eGFR) <15 mL/min or on dialysis
  • Signs and symptoms of increased risk of bleeding, including but not limited to: frequent nosebleeds, unexplained or worsening bruising, blood in urine or stool
  • Unwilling to avoid engaging in activities that may increase the risk of bleeding through body injury or bruising, during the study period (e.g., contact sports)

  • Baseline prolonged INR, defined as INR >1.4

    • If INR is elevated, but PT and aPTT are below the upper limit of normal (13.3 sec and 37.7 sec, respectively), then the subject may be cleared to receive the study drug at the discretion of one of the study physicians.
  • Platelets <100 x 109/L
  • History of stroke, or a history of gastrointestinal or intracranial bleeds

  • Use of any prescription medications, over-the-counter (OTC) medications, or herbal products that are strong inhibitors or inducers of CYP3A4 and/or P-gp within 14 days prior to Study Day 1 or anticipated need for such drugs during the study. Examples included:

    • Strong inducers of CYP3A4 (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort, etc.)
    • Strong inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, clarithromycin, etc.)
    • Antiplatelet and/or anticoagulant agents: heparin, aspirin** (see below), clopidogrel, prasugrel, non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, rivaroxaban, dabigatran, edoxaban
  • Pregnancy or breastfeeding
  • Liver disease with impaired synthetic function (INR >1.4, total bilirubin >1.2)
  • Evidence of acute kidney disease by the KDIGO criteria (>1.5 x baseline SCr, or >0.3 mg/dL increase in SCr, over past 48 hours
  • Unwillingness to forgo drinking alcohol during the study period due to heightened bleeding risk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nephrotic Syndrome Arm
Patients diagnosed with Nephrotic syndrome will be in this arm.
Drug: Apixaban 5 MG
1 - 5 mg tablet taken orally twice a day
Other Names:
  • Eliquis
Experimental: Healthy Arm
Healthy volunteers will be in this arm.
Drug: Apixaban 5 MG
1 - 5 mg tablet taken orally twice a day
Other Names:
  • Eliquis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Area Under the Curve (AUC (0-12)) is the area under the curve from time 0 to 12 hour after apixaban steady state concentration is reached.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Initial Dose Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
AUC (0-12) is the area under the curve from time 0 to 12 hour after the initial dose
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state Elimination of Half-Life of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Mean terminal phase plasma t½ of apixaban at steady-state
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose Elimination of Half-Life of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Mean terminal phase plasma t½ of apixaban after initial dose
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady-state Maximum Observed Plasma Concentration of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Maximum observed drug concentration in plasma after administration (Cmax) of apixaban at steady-state
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose Maximum Observed Plasma Concentration of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Maximum observed drug concentration in plasma after administration (Cmax) of apixaban after initial dose
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state Plasma Clearance as a Function of Bioavailability of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
CL/F of apixaban of apixaban at steady-state
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose Plasma Clearance (CL) as a Function of Bioavailability (F) of Apixaban
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
CL/F of apixaban of apixaban after initial dose
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Initial Thrombin Generation Assay (TGA)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Initial apixaban TGA concentrations. Thrombin generation assay is used to investigate hypo- or hypercoagulability.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state Thrombin Generation Assay (TGA)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Steady state apixaban TGA concentrations. Thrombin generation assay is used to investigate hypo- or hypercoagulability.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose Anti-Xa activity
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Initial apixaban dose Anti-Xa activity. Anti-Xa activity will be used to measure plasma apixaban levels.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state Anti-Xa activity
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Steady state apixaban dose Anti-Xa activity. Anti-Xa activity will be used to measure plasma apixaban levels.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose Activated Partial Thromboplastin Time (aPTT)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Initial apixaban dose aPTT. The activated partial thromboplastin time (aPTT) will be used to characterize the coagulation of the blood.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state Activated Partial Thromboplastin Time (aPTT)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Steady state apixaban dose aPTT. The activated partial thromboplastin time (aPTT) will be used to characterize the coagulation of the blood.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose International Normalised Ratio (INR)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Initial apixaban dose INR. INR is defined as the ratio of the participants prothrombin time and the normal mean prothrombin time. The INR will help determine the risk of coagulation.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state International Normalised Ratio (INR)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Steady state apixaban dose INR. INR is defined as the ratio of the participants prothrombin time and the normal mean prothrombin time. The INR will help determine the risk of coagulation.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Initial dose Prothrombin time (PT)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Initial apixaban dose PT. Prothrombin is defined as time taken by the blood to clot in the participants.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
Steady state Prothrombin time (PT)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Steady state apixaban dose PT. Prothrombin is defined as time taken by the blood to clot in the participants.
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
Total Adverse Events (AE)
Time Frame: From screening to Day 10 after initial study drug administration
Number of subjects experiencing AEs, bleeding-related AEs, serious adverse events (SAEs), or discontinuations due to AEs
From screening to Day 10 after initial study drug administration

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacogenetics and AUC0-12
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Associations between germline variants within genes that encode proteins that are central to apixaban metabolism and transport and AUC0-12
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Pharmacogenetics and CL/F
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Associations between germline variants within genes that encode proteins that are central to apixaban metabolism and transport and CL/F
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Pharmacogenetics and t1/2
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Associations between germline variants within genes that encode proteins that are central to apixaban metabolism and transport and t1/2
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Pharmacogenetics and anti-Xa
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Associations between germline variants within genes that encode proteins that are central to apixaban metabolism and transport and anti-Xa
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Pharmacogenetics and thrombin generation
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Associations between germline variants within genes that encode proteins that are central to apixaban metabolism and transport and thrombin generation
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Pharmacogenetics and Cmax
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Associations between germline variants within genes that encode proteins that are central to apixaban metabolism and transport and Cmax
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 1 & 8
Baseline Quantitative D-Dimer
Time Frame: Baseline at hour 0
Quantitative D-Dimer levels at baseline before first dose of apixaban
Baseline at hour 0
Quantitative D-Dimer at steady-state
Time Frame: Day 8 at hour 8
Quantitative D-Dimer levels at steady-state apixaban
Day 8 at hour 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of North Carolina, Chapel Hill

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
American College of Clinical Pharmacy

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel Crona, PharmD, PhD, University of North Carolina, Chapel Hill

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 14, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 22, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 22, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 18, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 20, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 26, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18-2233

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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