Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form

A Prospective, Single Dose, Randomized, Open-label, Crossover, Comparative Study to Establish Bioequivalence in Healthy Subjects Between the Puran T4® (Sanofi Aventis Farmacêutica Ltda) vs. the New Formulation of Levothyroxine (Eutirox NF® Merck) Administered Orally as 3 Tablets of 200 μg

The study was to verify if the test formulation of Levothyroxine sodium presents an equivalent rate and extension of absorption to the comparator formulation when administered with the same dosage and under fasting conditions and after baseline correction concentrations.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Puran T4®; Drug: Eutirox®

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Aparecida de Goiânia, Brazil
    • Instituto de Ciências Farmacêuticas de Estudos e Pesquisas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• To have freely agreed and signed the consent form, after all essential elements of the protocol have been clarified, before any procedure
• Body Mass Index (BMI) of the research participants must be comprised within the range of 18.50 to 27.00
• No abnormal findings on medical history that, in the opinion of the investigator, constitutes a risk or a contraindication for the participation of the participant in the study or that could interfere with the study objectives, conduct or evaluation
• Normal vital signs: heart rate between 50 and 100 beats per minute; Systolic pressure between 80 and 129 millimeters of mercury (mmHg); diastolic pressure between 50 and 89 mmHg; temperature between 36.0 and 37.0 degrees Celsius
• Electrocardiogram (ECG) normal (abnormalities, even if clinically not relevant, are not permitted [example {e.g.}: PR, QRS, QT, QTcF] should be within normal range, no conduction abnormalities etcetera [etc.])
• All values for biochemistry and hematology tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the Investigator
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Supplementary tests results out of the values considered as normal, unless considered clinically irrelevant
• Research participants who are submitted to surgery before the beginning of the study will be carefully evaluated by the doctor regarding the enrollment in the study complying to an exclusion period ranging from 4 to 8 weeks
• Positive test for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) in pre-study tests
• Participants with a history of hypersensitivity/allergy to study drug or excipients, history or presence of asthma or any serious allergy (requiring hospitalization or prolonged systemic treatment), any food allergy or intolerance which in the opinion of the Investigator represents a safety risk (e.g., iodine allergy, etc.)
• Has participated in any experimental trial or has taken any experimental drug within 6 months previous to this study (RDC [resolution of the collegiate board] Resolution 34, dated June 3, 2008)
• Participants that prior to the dosing takes any other medication and had not passed at least seven half-lives of elimination of the drug, in this case, be considered by the Principal Investigator the non-inclusion of the participant in the study. Participants taking medications known to affect thyroid hormone metabolism, e.g., oral contraceptives, hormonal implants, parenteral hormones, anabolic steroids, androgens, etc., or the bioavailability of levothyroxine like proton pump Inhibitors
• Has a history of alcohol abuse or has ingested alcohol 24 hours previous to the hospitalization period
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First Puran T4®, then Eutirox®; Participants received single oral dose of Puran T4® 600 micrograms (mcg) (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 1 followed by single oral dose of Eutirox® 600 mcg (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 2 under fasting conditions. A wash-out period of 70 days was maintained between the Treatment Periods 1 and 2.	Drug: Puran T4®; Participants who received a single oral dose of Puran T4® 600 mcg tablets (3 tablets of 200 mcg Levothyroxine sodium) in either Treatment Period 1 or 2 under fasting conditions.; Drug: Eutirox®; Participants who received a single oral dose of Eutirox® 600 mcg tablets (3 tablets of 200 mcg Levothyroxine sodium) in either Treatment Period 1 or 2 under fasting conditions.
Experimental: First Eutirox®, then Puran T4®; Participants received single oral dose of Eutirox® 600 mcg (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 1 followed by single oral dose of Puran T4® 600 mcg (3 tablets of 200 mcg Levothyroxine sodium) in Treatment Period 2 under fasting conditions. A wash-out period of 70 days was maintained between the Treatment Periods 1 and 2.	Drug: Puran T4®; Participants who received a single oral dose of Puran T4® 600 mcg tablets (3 tablets of 200 mcg Levothyroxine sodium) in either Treatment Period 1 or 2 under fasting conditions.; Drug: Eutirox®; Participants who received a single oral dose of Eutirox® 600 mcg tablets (3 tablets of 200 mcg Levothyroxine sodium) in either Treatment Period 1 or 2 under fasting conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium	Cmax was obtained from plasma concentration time curve. Maximum plasmatic concentration observed adjusted by basal level correction was reported.	Pre-dose, 24, 36, 48 and 72 hours post-dose
Baseline Corrected Area Under The Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC0-72 [Adj]) of Levothyroxine Sodium	The AUC 0-72 was defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours post-dose. Area under the plasma curve from time 0 hours to time 72 hours adjusted by basal levels correction was reported.	Pre-dose, 24, 36, 48 and 72 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Maximum Plasma Concentration (Tmax) of Levothyroxine Sodium	Tmax was obtained from plasma concentration time curve.	Pre-dose, 24, 36, 48 and 72 hours post-dose
Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC 0-72) of Levothyroxine Sodium	The AUC 0-72 was defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours post-dose.	Pre-dose, 24, 36, 48 and 72 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Levothyroxine Sodium	Cmax was obtained from plasma concentration time curve.	Pre-dose, 24, 36, 48 and 72 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Actual): September 11, 2019
• Study Completion (Actual): September 11, 2019

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Levothyroxine; Eutirox®; Puran T4®
• Other Study ID Numbers: MS200125_0014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No