Effect of Age, Weight and Sex on Levothyroxine Pharmacokinetics

Hypothyroidism Treatment in Aging and Thyroid Cancer

This study was a prospective, single-center, open-label, non-randomized, pharmacokinetic study using stable isotope carbon-13 labeled levothyroxine

Study Overview

• Status: Completed
• Conditions: Hypothyroidism Primary
• Intervention / Treatment: Drug: Administration of stable Isotope 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 Type: Interventional
• Enrollment (Actual): 41
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stable isotope arm; Measurement of blood levels of labelled levothyroxine after administration of single oral dose of stable isotope levothyroxine	Drug: Administration of stable Isotope labeled levothyroxine; Administration of single dose of stable isotope carbon-13 labeled levothyroxine and measurement of blood levels of stable isotope-labeled levothyroxine; Other Names: levothyroxine or synthroid

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	120 hours
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.	120 hours
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.	120 hours

Collaborators and Investigators

• Sponsor: Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2011
• Primary Completion (Actual): November 30, 2013
• Study Completion (Actual): July 26, 2016

Study Registration Dates

• First Submitted: March 27, 2017
• First Submitted That Met QC Criteria: March 30, 2017
• First Posted (Actual): April 5, 2017

Study Record Updates

• Last Update Posted (Actual): April 6, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hypothyroidism
• Other Study ID Numbers: 2010-572

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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