Bioequivalence Study of Levothyroxine Sodium Tablets 100 mcg

Comparative Bioavailability Study of Levothyroxine Sodium Tablets 100 mcg in Healthy Volunteers

The objective of this study is to establish the bioequivalence of two levothyroxine formulations through the estimation of T4 levels in serum samples after baseline correction, according to Food and Drugs Administration (FDA), World Health Organization (WHO) and Colombian National Vigilance Institute for Drugs and Food (INVIMA) guidelines.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Drug Levothyroxine 100 mcg; Drug: Drug Eutirox 100 mcg

Detailed Description

Levothyroxine (T4) is used to treat patients with hypothyroidism and may often result in lifelong therapy. Its physiologically active metabolite is tri-iodothyronine (T3). Levothyroxine is also endogenously produced in the body. Since small changes in levothyroxine administration (e.g. change in brand or formulation) can cause significant changes in serum thyroid stimulating hormone (TSH) concentrations, precise and accurate TSH control is critical to avoid potential adverse iatrogenic effects. Tecnoquimicas modified its Levothyroxine tablets formulation in order to comply with new pharmacopeial specifications. It will then evaluate the impact on drug product performance based on pharmacokinetic (PK) measures of total serum T4 and total serum T3 of the new formulation of levothyroxine (Test formulation) relative to the reference formulation from Merck (Reference formulation)

This will be a single-center, open-label, two-period, two-treatment, two-sequence, randomized, single-dose, crossover study. 80 healthy adults will be randomized to receive a single dose (6 x 100 mcg tablets = 600 mcg) of the test formulation of levothyroxine and reference formulation of levothyroxine separately in each treatment period. There will be two treatment sequences (AB, BA) and a 42 day washout between the two treatment periods.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Entre Ríos
    • Paraná, Entre Ríos, Argentina
      • DominguezLab

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:

• Signed Informed Consent
• Healthy volunteers according to antecedents, clinical evaluation, biochemical tests and other complimentary tests
• Sex: both (male and female, homogenously distributed)
• Age: 18 to 50 years old
• BMI: 18 to 30 kg/m2
• Non smokers from at least 3 months

Exclusion Criteria:

• History of liver disease, kidney disease or conditions of psychiatric origin.
• History of drug or alcohol abuse in the last two years.
• Ingestion of other drugs the 2 weeks prior to the start of the study.
• History of seizure disorders, depressive disorders, cardiovascular diseases, hematological, metabolic, vesicular or other, that the Principal Investigator judges clinically significant.
• Abnormal electrocardiogram (EKG).
• Hypersensitivity to Levothyroxine sodium or to excipients (from formulations to test).
• Positive HIV test; hepatitis B and C.
• Positive urine drug dose of abuse.
• Having participated in another research study in the last 6 months.
• Having donated blood within the 3 months prior to the start of the study.
• Clinically significant abnormal laboratory test results.
• Abnormal results outside the reference values for thyroid function (T3, T4, TSH, anti-TPO antibodies).
• Female volunteers who are breastfeeding during the study period.
• Positive beta-HCG test in female volunteers.
• Volunteers who must start a scheduled medical or pharmacological treatment outside the this Protocol.
• Volunteers who do not maintain the conditions of fasting and food intake in the pre-established schedules.
• Volunteers who do not avoid the intake of coffee, tea, grapefruit, cola and / or alcoholic beverages during the 48 h preceding the study.
• Volunteers on a special diet in the last 28 days (eg vegetarian diet, etc.).
• Volunteers with clinically significant allergies to food, medication, etc.
• Non-cooperative volunteers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Formulation of Levothyroxine; Levothyroxine sodium tablets 100 mcg Single dose of 600 mcg administered in dosing period 1 or 2	Drug: Drug Levothyroxine 100 mcg; Administration of a 600 mcg levothyroxine dose
Active Comparator: Reference formulation of Levothyroxine; Eutirox 100 mcg Single dose of 600 mcg administered in dosing period 1 or 2	Drug: Drug Eutirox 100 mcg; Administration of a 600 mcg levothyroxine dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(AUC) Area Under the Curve 0-48 for T4	-30 min., -15 min., 0 hour (h ) pre-dose; 30 min., 1 h, 1.30 h, 2 h, 2.30 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h , 48 hours	[Time Frame: From 0 to 48 hours]
(Cmax) Maximum concentration 0-48 for T4	-30 min., -15 min., 0 hour ( h) pre-dose; 30 min., 1 h, 1.30 h, 2 h, 2.30 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h , 48 hours	[Time Frame: From 0 to 48 hours]

Collaborators and Investigators

• Sponsor: Tecnoquimicas
• Collaborators: DominguezLab

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: PRO-BEQ-LEVO-007-V.01

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