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Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics

Primary Purpose

Hypothyroidism Primary

Status
Completed
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Administration of stable Isotope labeled levothyroxine
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Hypothyroidism Primary

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • age >21 years at the time of consent
  • euthyroidism while undergoing treatment with LT4
  • no other serious illness
  • ability to give written informed consent.

Exclusion Criteria:

  • baseline hematocrit lower than 28.0%
  • TSH greater than 4.5 mIU/L
  • kidney dysfunction
  • concomitant use of drugs that affect thyroidal axis interactions

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Stable isotope arm

    Arm Description

    Measurement of blood levels of labelled levothyroxine after administration of single oral dose of stable isotope levothyroxine

    Outcomes

    Primary Outcome Measures

    CL/F
    oral clearance rate (defined as the ratio of dose administered to AUC0-∞)
    V/F
    apparent volume of distribution (estimated by CL/F/ λ)
    t-half
    the half-life of the terminal disposition phase (t-half) estimated by ln(2)/λ .

    Secondary Outcome Measures

    CL/F analysed by age groups
    CL/F will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach.
    V/F analysed by age groups
    V/F will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach.
    t-half by age groups
    t-half will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach.

    Full Information

    First Posted
    March 27, 2017
    Last Updated
    April 4, 2017
    Sponsor
    Georgetown University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03102177
    Brief Title
    Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics
    Official Title
    Hypothyroidism Treatment in Aging and Thyroid Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    May 31, 2011 (Actual)
    Primary Completion Date
    November 30, 2013 (Actual)
    Study Completion Date
    July 26, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Georgetown University

    4. Oversight

    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.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study was a prospective, single-center, open-label, non-randomized, pharmacokinetic study using stable isotope carbon-13 labeled levothyroxine
    Detailed Description
    Setting The study was conducted on the clinical research unit of an academic medical center. Participants Adults of any age being treated with levothyroxine for hypothyroidism were studied. Interventions A single dose of 13C- LT4 was administered to hypothyroid subjects taking levothyroxine replacement. Main Outcomes and Measures Eighteen serial plasma samples were collected. One sample was obtained before the 13C- LT4 dose and the remainder over the 312-hour period post-dosing. 13C- LT4 concentration was quantified using validated liquid chromatography tandem mass spectrometry methods. Pharmacokinetic analysis was conducted using linear log trapezoidal non-compartmental analysis using Phoenix 6.4.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hypothyroidism Primary

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    Open label prospective study
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    41 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Stable isotope arm
    Arm Type
    Experimental
    Arm Description
    Measurement of blood levels of labelled levothyroxine after administration of single oral dose of stable isotope levothyroxine
    Intervention Type
    Drug
    Intervention Name(s)
    Administration of stable Isotope labeled levothyroxine
    Other Intervention Name(s)
    levothyroxine or synthroid
    Intervention Description
    Administration of single dose of stable isotope carbon-13 labeled levothyroxine and measurement of blood levels of stable isotope-labeled levothyroxine
    Primary Outcome Measure Information:
    Title
    CL/F
    Description
    oral clearance rate (defined as the ratio of dose administered to AUC0-∞)
    Time Frame
    120 hours
    Title
    V/F
    Description
    apparent volume of distribution (estimated by CL/F/ λ)
    Time Frame
    120 hours
    Title
    t-half
    Description
    the half-life of the terminal disposition phase (t-half) estimated by ln(2)/λ .
    Time Frame
    120 hours
    Secondary Outcome Measure Information:
    Title
    CL/F analysed by age groups
    Description
    CL/F will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach.
    Time Frame
    120 hours
    Title
    V/F analysed by age groups
    Description
    V/F will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach.
    Time Frame
    120 hours
    Title
    t-half by age groups
    Description
    t-half will be compared in adults (age ≤60 years) versus elderly (age>60 years) using Wilcoxon signed-rank test using significance level of α = 0.05. Additionally, these PK parameters were regressed against age (as a continuous covariate). Sex (male or female), weight (as a continuous covariate), and body mass index (BMI) (as a continuous covariate) will be considered using a stepwise linear regression approach.
    Time Frame
    120 hours

    10. Eligibility

    Sex
    All
    Gender Based
    Yes
    Minimum Age & Unit of Time
    21 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: age >21 years at the time of consent euthyroidism while undergoing treatment with LT4 no other serious illness ability to give written informed consent. Exclusion Criteria: baseline hematocrit lower than 28.0% TSH greater than 4.5 mIU/L kidney dysfunction concomitant use of drugs that affect thyroidal axis interactions

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics

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