Evaluation of Amlodipine Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

NCT03722381 | Withdrawn FDA Drug

• 1 other identifier: HUM00143303
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hemodialysis; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Characterize the Non-renal clearance phenotype and genotype

  30 minutes

• Characterize the Post-dialysis Rebound

  post-dialysis (30 minutes, 2 hours and 4 hours)

Interventions

Amlodipine Besylate DRUG

Pharmacokinetics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Ambulatory in-center hemodialysis patients

You may qualify if:

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

You may not qualify if:

• Any condition that would not allow for arm BP to be taken
• Hemoglobin \< 9.5 g/dL on most recent lab prior to study
• 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).

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan Dialysis

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Interventions

Amlodipine

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Amy Pai, PharmD Associate Professor

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 26, 2018
• Study Start: January 1, 2020
• Primary Completion: January 30, 2020
• Study Completion: January 30, 2020
• Last Updated: January 31, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)