Pharmacokinetics of Apixaban in Nephrotic Syndrome

NCT02599532 | Completed Phase 1 FDA Drug

• 2 other identifiers: 14-1455550KR161709
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Nephrotic Syndrome; Proteinuria

Keywords

Apixaban; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Area under the concentration versus time curve after single dose (AUC) of apixaban

  Predose; 0.5, 1, 3, 4, 6, and 8 hours (hr) postdose on Day 1; 24 hours postdose on Day 2

Secondary Outcomes (5)

• Mean terminal phase plasma half-life (t½)

  Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2

• Apparent oral clearance (CL/F)

  Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2

• Maximum observed drug concentration in plasma after single dose administration (Cmax)

  Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2

• Thrombin Generation Assay

  Predose; 3 and 6 hours postdose on Day 1; 24 hours postdose on Day 2

• Anti-Xa activity

  Predose; 0.5, 1, 3, 4, 6, and 8 hours postdose on Day 1; 24 hours postdose on Day 2

Other Outcomes (1)

• Proportion of germline variants in genes involved in apixaban metabolism and clearance

  DNA extracted from whole blood specimens will be genotyped at the conclusion of enrollment, approximately 12 months.

Study Arms (2)

Nephrotic syndrome

OTHER

Subjects with nephrotic syndrome will receive a single dose of apixaban 10 mg and will subsequently have blood drawn at 0, 0.5, 1, 3, 4, 6, 8, 24 hours after drug administration.

Drug: apixaban

Non-nephrotic syndrome

OTHER

Subjects without nephrotic syndrome will receive a single dose of apixaban 10 mg and will subsequently have blood drawn at 0, 0.5, 1, 3, 4, 6, 8, 24 hours after drug administration.

Drug: apixaban

Interventions

apixaban DRUG

Study subjects will be given a single-dose of apixaban 10 mg.

Also known as: Eliquis

Nephrotic syndrome; Non-nephrotic syndrome

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Study subjects:
• Between 18 and 79 years old
• Confirmed diagnosis of Nephrotic Syndrome, with at least one of the following:
• \. Nephrotic-range proteinuria, defined as \>3.5 g/24 hours or UPC \>3.5 (confirmed within 1 month prior to scheduled study visit)
• \. 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)

You may not qualify if:

• 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)
• 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.)

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• North Carolina Translational and Clinical Sciences Institute: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Nephrotic Syndrome; Proteinuria

Interventions

apixaban

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel Crona, PharmD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Vimal Derebail, MD, MPH

  University of North Carolina, Chapel Hill

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2015
• First Posted: November 6, 2015
• Study Start: April 30, 2017
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: July 24, 2019

Record last verified: 2019-07

Locations

US (1)