Evaluation of Amlodipine Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

The current study will evaluate the plasma pharmacokinetics of amlodipine in a cohort of 8 adult volunteers who are receiving regular hemodialysis treatment (HD) 3 days a week for 4 hours each day and have been taking a total daily dose of 5-10 mg of amlodipine besylate for >30 days as part of their usual care. Blood sampling will occur over 13 hours, with frequent sampling during HD and in the 4 hours after termination of HD treatment. The 8 subjects will all receive their prescribed total daily dose of 5-10 mg 5 hours prior to HD treatment. The pre-HD sample will also be sent for pharmacogenomics genotyping. Safety and pharmacodynamic assessments (blood pressure (BP) and heart rate (HR) assessments) will be performed throughout the study. Axiom Precision Medicine Research Array (Affymetrix, Santa Clara, CA) will be used to evaluate genotype of CYP3A4. CYP3A4 phenotype will be evaluated using the ratio of parent drug to metabolite. Non-compartmental analyses will be performed to compare maximum concentrations (Cmax), time to maximum concentration and area under the curve from time 0 to the last measurable sample (AUClast) between the two phases. Compartmental analyses will be performed to construct a model to explain time-dependent changes in amlodipine clearance. Monte Carlo simulations will be performed to compare amlodipine pharmacokinetic profiles on and off HD.

Study Overview

• Status: Withdrawn
• Conditions: Hemodialysis; Pharmacokinetics
• Intervention / Treatment: Drug: Amlodipine Besylate

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Dialysis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Ambulatory in-center hemodialysis patients

Description

Inclusion Criteria:

1. 18 years of age or older
2. Indwelling tunneled catheter, AVF, AVG that is currently used for hemodialysis
3. Receiving in-center hemodialysis 3 days a week for 3-4.5 hours each treatment
4. Taking a total daily dose of 5-10 mg of amlodipine as prescribed by their physician
5. Hemoglobin ≥ 9.5 g/dL on most recent laboratory assessment prior to study

Exclusion Criteria:

1. Any condition that would not allow for arm BP to be taken
2. Hemoglobin < 9.5 g/dL on most recent lab prior to study
3. Patient is on a CYP3A4 inhibitor (most common in HD population include: amiodarone, clarithromycin, cyclosporine, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, nefazodone, tamoxifen, verapamil, and grapefruit juice).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use pharmacokinetics to characterize the plasma concentration of amlodipine and its metabolite, 2-([4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl- 2-pyridyl]methoxy) acetic acid	Use pharmacokinetics to characterize the change in plasma concentration of amlodipine and its metabolite, 2-([4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl- 2-pyridyl]methoxy) acetic acid during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the Non-renal clearance phenotype and genotype	Evaluate the non-renal clearance of amlodipine in patients on HD.	30 minutes
Characterize the Post-dialysis Rebound	Simulate change in predicted rebound of metoprolol concentrations	post-dialysis (30 minutes, 2 hours and 4 hours)

Collaborators and Investigators

• Sponsor: University of Michigan

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 30, 2020
• Study Completion (Anticipated): January 30, 2020

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine
• Other Study ID Numbers: HUM00143303

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
• product manufactured in and exported from the U.S.: Yes