Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

NCT03612180 | Completed FDA Drug

• 1 other identifier: HUM00138192
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The current study will evaluate the plasma pharmacokinetics of metoprolol 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 25-200 mg of metoprolol succinate for \>30 days as part of their usual care. Blood sampling will occur over 10 hours, with frequent sampling during HD and in the 4 hours after termination of HD treatment. The 8 subjects will all receive their prescribed dose (25-200 mg total daily dose) 2 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 CYP2D6. CYP2D6 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 metoprolol clearance. Monte Carlo simulations will be performed to compare metoprolol pharmacokinetic profiles on and off HD.

Conditions

Hemodialysis; Pharmacokinetics

Outcome Measures

Primary Outcomes (7)

• Plasma pharmacokinetics-Maximal Plasma Concentration

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Plasma pharmacokinetics-Time to Maximal Plasma Concentration

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Plasma Pharmacokinetics-Area under the concentration time curve (AUC)

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Plasma Pharmacokinetics-Clearance

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Plasma Pharmacokinetics-Volume of Distribution

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Plasma Pharmacokinetics-elimination rate constant

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Plasma Pharmacokinetics-half-life

  Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol 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)

• Non-renal clearance phenotype and genotype

  Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)

• Post-dialysis Rebound

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

Interventions

Metoprolol Succinate 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:

• Age \> 18 years
• 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 25-200 mg metoprolol succinate 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 CYP2D6 inhibitor (most common in HD population amiodarone, bupropion, cinacalcet, diphenhydramine, fluoxetine, paroxetine)

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan Dialysis

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Interventions

Metoprolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

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: July 12, 2018
• First Posted: August 2, 2018
• Study Start: June 30, 2018
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: July 29, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)