Pharmacokinetics of Apixaban in Nephrotic Syndrome

• Status: Completed
• Trial end date: 2019-06-28
• Target enrollment: 0
• Participant gender: All

Summary

This study is to investigate the pharmacokinetics and pharmacodynamics of apixaban in nephrotic syndrome.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: North Carolina Translational and Clinical Sciences Institute
• Treatments: Apixaban

Criteria

• Inclusion Criteria:

• Study subjects:

• Between 18 and 79 years old

• Confirmed diagnosis of Nephrotic Syndrome, with at least one of the following:

• 1. Nephrotic-range proteinuria, defined as >3.5 g/24 hours or UPC >3.5 (confirmed within 1 month prior to scheduled study visit)

• 2. Hypoalbuminemia, defined as <3 g/dL (confirmed within 1 month prior to scheduled study visit)

• Control subjects:

• Between 18 and 79 years old

• Normal albumin levels (≥3.5 mg/dL)

• No proteinuria (UPC <0.15)

• Exclusion criteria:

• Age <18 or ≥ 80 years old

• SCr ≥ 1.5 AND weight ≤ 60kg (these subjects would receive a reduce dose of apixaban, per drug labeling)

• On dialysis

• Baseline prolonged PT/INR, PTT (as defined by greater than the upper limit of normal)

• INR will be used as the primary lab value to evaluate bleeding risk (e.g. a patient presenting with an INR within normal limits, but prolonged PT or PTT, will not meet this exclusion criterion and will still be eligible for the study)

• Reference Ranges

• INR: >1.4

• PT: >13.3 sec

• aPTT: >37.7 sec

• Platelets <100

• History of GI bleed

• History of intracranial bleed

• History of stroke

• Use of (but not limited to) the following medications within the past 14 days:

• 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, NSAIDs, warfarin, rivaroxaban, dabigatran, edoxaban

• Selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)

• Pregnancy/breastfeeding

• Liver disease with impaired synthetic function (INR >1.4, total bilirubin >1.2)

• Congestive heart failure

Special consideration for patients on aspirin: for patients on chronic low-dose aspirin therapy, we will allow a 7 day wash out period. This will only be allowed for patients who are taking aspirin as primary prophylaxis or for unclear indications. Patients who are on aspirin therapy for following indications will be excluded: primary prophylaxis of stroke due to atrial fibrillation, secondary prevention of stroke or myocardial infarction, history of coronary artery disease or peripheral vascular disease. For patients who meet the potential criteria for the 7-day wash out, their medical history will be reviewed by one of the clinician investigators to ensure that it is safe and appropriate to hold the agent.

Those subjects taking aspirin for the following reasons will be excluded:

• Primary stroke prevention from atrial fibrillation

• Secondary prevention due to prior stroke, heart attack or cardiac stent

• Existing heart disease or peripheral vascular disease.