Clinical trial NCT03722381: Evaluation of Amlodipine Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis
Official title: Evaluation of Amlodipine Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Hemodialysis
Pharmacokinetics
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2018-10-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Ambulatory in-center hemodialysis patients

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.


Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Secondary outcomes:
measure: Characterize the Non-renal clearance phenotype and genotype
timeFrame: 30 minutes
measure: Characterize the Post-dialysis Rebound
timeFrame: post-dialysis (30 minutes, 2 hours and 4 hours)
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Dialysis
state: Michigan
Study officials:
References: