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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04037748
Recruitment Status : Completed
First Posted : July 30, 2019
Results First Posted : September 29, 2020
Last Update Posted : September 29, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Puran T4® Drug: Eutirox® Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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
Actual Study Start Date : June 25, 2019
Actual Primary Completion Date : September 11, 2019
Actual Study Completion Date : September 11, 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium [ Time Frame: Pre-dose, 24, 36, 48 and 72 hours post-dose ]
    Cmax was obtained from plasma concentration time curve. Maximum plasmatic concentration observed adjusted by basal level correction was reported.

  2. Baseline Corrected Area Under The Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC0-72 [Adj]) of Levothyroxine Sodium [ Time Frame: Pre-dose, 24, 36, 48 and 72 hours post-dose ]
    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.


Secondary Outcome Measures :
  1. Time to Reach Maximum Plasma Concentration (Tmax) of Levothyroxine Sodium [ Time Frame: Pre-dose, 24, 36, 48 and 72 hours post-dose ]
    Tmax was obtained from plasma concentration time curve.

  2. Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC 0-72) of Levothyroxine Sodium [ Time Frame: Pre-dose, 24, 36, 48 and 72 hours post-dose ]
    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.

  3. Maximum Observed Plasma Concentration (Cmax) of Levothyroxine Sodium [ Time Frame: Pre-dose, 24, 36, 48 and 72 hours post-dose ]
    Cmax was obtained from plasma concentration time curve.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04037748


Locations
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Brazil
Instituto de Ciências Farmacêuticas de Estudos e Pesquisas
Aparecida de Goiânia, Brazil
Sponsors and Collaborators
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
  Study Documents (Full-Text)

Documents provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany:
Additional Information:
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Responsible Party: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT04037748    
Other Study ID Numbers: MS200125_0014
First Posted: July 30, 2019    Key Record Dates
Results First Posted: September 29, 2020
Last Update Posted: September 29, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany:
Eutirox®
Puran T4®
Levothyroxine