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

NCT04278729 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18-2233
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Nephrotic Syndrome; Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban

  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 Outcomes (18)

• Initial Dose Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Apixaban

  Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose

• Steady state Elimination of Half-Life of Apixaban

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

• Initial dose Elimination of Half-Life of Apixaban

  Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose

• Steady-state Maximum Observed Plasma Concentration of Apixaban

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

• Initial dose Maximum Observed Plasma Concentration of Apixaban

  Predose; 1, 2, 3, 4, 6, and 8 hours (hr) postdose

Other Outcomes (8)

• Pharmacogenetics and AUC0-12

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

• Pharmacogenetics and CL/F

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

• Pharmacogenetics and t1/2

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

Study Arms (2)

Nephrotic Syndrome Arm

EXPERIMENTAL

Patients diagnosed with Nephrotic syndrome will be in this arm.

Drug: Apixaban 5 MG

Healthy Arm

EXPERIMENTAL

Healthy volunteers will be in this arm.

Drug: Apixaban 5 MG

Interventions

Apixaban 5 MG DRUG

1 - 5 mg tablet taken orally twice a day

Also known as: Eliquis

Healthy Arm; Nephrotic Syndrome Arm

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• American College of Clinical Pharmacy: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

MeSH Terms

Conditions

Nephrotic Syndrome; Glomerulonephritis, Membranous

Interventions

apixaban

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases

Study Officials

• Daniel Crona, PharmD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 20, 2020
• Study Start: April 14, 2021
• Primary Completion: September 22, 2023
• Study Completion: September 22, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)