Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics

Early Phase 1

Completed

• Conditions: Hypothyroidism Primary
• Interventions: Drug: Administration of stable Isotope labeled levothyroxine

• Registration Number: NCT03102177
• Lead Sponsor: Georgetown University

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.

Study Timeline

• Study Start: 2011-05-31
• Primary Completion: 2013-11-30
• Study Completion: 2016-07-26
• Status Verified: 2017-03
• Study First Submitted: 2017-03-27
• Study First Submitted QC: 2017-03-30
• Last Update Submitted: 2017-04-04
• Study First Posted: 2017-04-05
• Last Update Posted: 2017-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stable isotope arm	Administration of stable Isotope labeled levothyroxine	Measurement of blood levels of labelled levothyroxine after administration of single oral dose of stable isotope levothyroxine

Primary Outcome Measures

Name	Time	Method
CL/F	120 hours	oral clearance rate (defined as the ratio of dose administered to AUC0-∞)
V/F	120 hours	apparent volume of distribution (estimated by CL/F/ λ)
t-half	120 hours	the half-life of the terminal disposition phase (t-half) estimated by ln(2)/λ .

Secondary Outcome Measures

Name	Time	Method
V/F analysed by age groups	120 hours	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	120 hours	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.
CL/F analysed by age groups	120 hours	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.