- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04278729
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
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
22
Phase
- 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
- Name: Chris Ramdass, PharmD
- Phone Number: 5706206316
- Email: cramdass@unc.edu
Study Locations
-
-
North Carolina
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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
Ages Eligible for Study
16 years to 77 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 |
Intervention / Treatment |
---|---|
Experimental: Nephrotic Syndrome Arm
Patients diagnosed with Nephrotic syndrome will be in this arm.
|
1 - 5 mg tablet taken orally twice a day
Other Names:
|
Experimental: Healthy Arm
Healthy volunteers will be in this arm.
|
1 - 5 mg tablet taken orally twice a day
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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
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CL/F of apixaban of apixaban at steady-state
|
Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
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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
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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
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Steady state Thrombin Generation Assay (TGA)
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
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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
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Initial dose Anti-Xa activity
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose
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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
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Steady state Anti-Xa activity
Time Frame: Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose approximately on Day 8
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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
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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
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Number of subjects experiencing AEs, bleeding-related AEs, serious adverse events (SAEs), or discontinuations due to AEs
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From screening to Day 10 after initial study drug administration
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Other Outcome Measures
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
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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
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Quantitative D-Dimer levels at baseline before first dose of apixaban
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Baseline at hour 0
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Quantitative D-Dimer at steady-state
Time Frame: Day 8 at hour 8
|
Quantitative D-Dimer levels at steady-state apixaban
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Day 8 at hour 8
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- 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)
April 14, 2021
Primary Completion (Actual)
September 22, 2023
Study Completion (Actual)
September 22, 2023
Study Registration Dates
First Submitted
February 18, 2020
First Submitted That Met QC Criteria
February 18, 2020
First Posted (Actual)
February 20, 2020
Study Record Updates
Last Update Posted (Actual)
September 26, 2023
Last Update Submitted That Met QC Criteria
September 25, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Kidney Diseases
- Urologic Diseases
- Disease
- Nephritis
- Glomerulonephritis
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Syndrome
- Nephrotic Syndrome
- Nephrosis
- Glomerulonephritis, Membranous
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Factor Xa Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Apixaban
Other Study ID 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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