HealthyPhase 1NCT04037748

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

A Phase 1 study testing Puran T4® and Eutirox® in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Puran T4® and Eutirox®
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 72 participants
Where: 1 siteBrazil
Study dates: 25 Jun 2019to 11 Sep 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Instituto de Ciências Farmacêuticas de Estudos e Pesquisas
Aparecida de Goiânia

Other trials in Brazil

About this study

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

Conditions: Healthy
Being tested: Puran T4®, Eutirox®
Keywords: Eutirox®, Puran T4®, Levothyroxine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Puran T4®Drug
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.
Eutirox®Drug
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.

Study groups in NCT04037748
Study group	Role	What they receive
First Puran T4®, then Eutirox®	Experimental	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. Receives: Drug: Puran T4®; Drug: Eutirox®
First Eutirox®, then Puran T4®	Experimental	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. Receives: Drug: Puran T4®; Drug: Eutirox®

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Pre-dose, 24, 36, 48 and 72 hours post-dose

Secondary outcomes (3)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Jun 201911 Sep 2019

First posted30 Jul 2019
Study start25 Jun 2019
Primary completion11 Sep 2019
Study completion11 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04037748
Sponsor's protocol ID: MS200125_0014
Status last verified: Aug 2020
First submitted: 26 Jul 2019
Last updated: 29 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04037748
Acronym / sponsor ID: MS200125_0014
Conditions: Healthy
Keywords: Eutirox®, Puran T4®, Levothyroxine
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 25 Jun 2019 (actual)
Primary completion: 11 Sep 2019 (actual)
Study completion: 11 Sep 2019 (actual)
First posted: 30 Jul 2019 (actual)
Results: Posted 29 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
First Puran T4®, then Eutirox®	Experimental	Drug: Puran T4®, Drug: 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.
First Eutirox®, then Puran T4®	Experimental	Drug: Puran T4®, Drug: Eutirox®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.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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.])

Key exclusion criteria (8 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	First Eutirox®, then Puran T4®, First Puran T4®, then Eutirox®
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.	Drug	First Eutirox®, then Puran T4®, First Puran T4®, then Eutirox®

Primary outcome

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.
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.

3 secondary outcomes

Time to Reach Maximum Plasma Concentration (Tmax) of Levothyroxine Sodium
Time frame: 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
Time frame: Pre-dose, 24, 36, 48 and 72 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Levothyroxine Sodium
Time frame: Pre-dose, 24, 36, 48 and 72 hours post-dose

Results and safety

Results posted to the registry on 29 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
First Puran T4®, Then Eutirox®	36	28
First Eutirox®, Then Puran T4®	36	30

Primary outcome: Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium

Time frame: Pre-dose, 24, 36, 48 and 72 hours post-dose. Mean (Standard Deviation). Unit: Nanogram per milliliter (ng/mL)

Measure	Puran T4® n = 55	Eutirox® n = 55
Value	67.258 (19.654)	60.552 (13.61)

Puran T4® vs Eutirox®: Geometric least squares (LS) mean ratio: 90.8 (90% CI 86.3 to 95.6)

Population analysed: Pharmacokinetic (PK) analysis set included all participants who completed both periods and had valid PK parameters in both.

Primary outcome: 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. Mean (Standard Deviation). Unit: Hour* ng/mL

Measure	Puran T4® n = 55	Eutirox® n = 55
Value	2682.371 (795.263)	2516.055 (716.575)

Puran T4® vs Eutirox®: Geometric least squares (LS) mean ratio: 93.7 (90% CI 88.2 to 99.5)

Population analysed: PK analysis set included all participants who completed both periods and had valid PK parameters in both.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 79 Days; Participants were assessed for adverse events for the entire study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Puran T4	0 of 72 (0%)	2 of 72 (2.8%)	0 of 72
Eutirox®	0 of 72 (0%)	5 of 72 (6.9%)	0 of 72

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Trial Awareness and Transparency websiteLink provided by the sponsor.
Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
Individual participant dataSharing planned: No. 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Puran T4® and Eutirox® in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium (time frame: Pre-dose, 24, 36, 48 and 72 hours post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04037748.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2020.