Clinical trial NCT03979274: A Comparative Study of New Formulation and Approved Formulation for Levothyroxine in Healthy Volunteers
Official title: Prospective, Single Dose, Randomized, Open Label, Comparative, Cross-study to Establish Bioequivalence Between the New Formulation and the Approved Formulation for Levothyroxine (Eutirox® From Merck, S. A. de C. V.) Given as 3 Tablets of 200 μg p.o. in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Eutirox
Levothyroxine
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2019-06-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The study investigated the bioequivalence between the new and the approved formulation for levothyroxine.


Eligibility criteria: Inclusion Criteria:

* Participants who have provided their written consent prior to any study-related activity
* Ethnic origin: Mexicans
* Body mass index from 18 to 27 kilogram per meter square (kg/m\^2)
* Normal vital signs (includes heart rate between 50 and 100 beats per minute, respiratory rate between 12 and 20 per minute, systolic blood pressure between 80 and 129 milimeter of mercury (mmHg) , diastolic blood pressure between 50 and 80 mmHg and temperature between 36.0 degree celsius and 37.0 degree celsius. The measurement will be made according to the instructive BE-IT-005 Medición de signos vitales)
* Normal electrocardiogram \[ECG\]. No abnormalities are allowed, even though they are not relevant (PR, QRS, QT, QTcF should be within normal range; no conduction abnormalities are allowed, etcetera (etc)
* All values in blood and urine tests should be within the normal range or showing no clinically relevant deviation as judged by the Investigator
* Participants with thyroid panel results within normal range (T3 and T4 total and free, as well as thyroid-stimulating hormone (TSH) should be within the normal range)
* Non-smoker at least in the last 3 months
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participation in the clinical study within 90 days prior to the first dose of the study drug
* History of hypersensitivity to the study drug or its excipients
* History or current asthma or any severe allergy (which requires hospitalization or prolonged therapy), allergy or intolerance to any food that, in the opinion of the investigator, poses a safety risk (allergy to iodine)
* History of cardiovascular, renal, liver, metabolic, gastrointestinal, neurological, endocrine, hematopoietic (any type of anemia) conditions, mental disorder or organic abnormalities that may affect the pharmacokinetic study of the study drug
* Any medical or surgical condition, including findings in the medical history or clinical assessment prior to the study, that in the opinion of the investigator poses a risk or contraindication for the participants participation in the study and may affect the study objectives, conduct or analysis
* History or presence of alcohol abuse (average daily intake not higher than 3 units or weekly intake not higher than 21 units; 1 unit is equivalent to 340 mililiter (mL) of beer, 115 mL of wine or 43 mL of prepared drinks), psychoactive substances or chronic use of drugs
* Participants who have been exposed to agents knows by inducing or inhibiting the liver enzymatic systems or who have taken potentially toxic drugs within the last 30 days to the study start-up
* Participants who take drugs affecting the metabolism of the thyroid hormone, such as: oral contraceptives, hormonal implants, parenteral hormones, steroids, anabolic drugs, androgens, etc., or any drug affecting the levothyroxine's bioavailability such as the proton pump inhibitors or multivitamins, nutritional supplements or herbal products that may affect the study, except for the occasional use of paracetamol
* Participants who have been hospitalized for any reason within the 60 days prior to the study start-up or who have been severely ill within the last 30 days prior to the study start-up
* Participants who have donated or lost 450 mL of blood within the last 60 days prior to the study start-up
* Participants non- smokers, who have smoked tobacco, cigarettes or consumed coffee, snuff or drinks containing xanthines such as caffeine, (tea, cocoa, chocolate, matte, cola, etc.) theobromine, theophylline, among others, affecting the pharmacokinetics of the drug in assessment, drinking alcohol, or charcoal-grilled foods consumed within twenty-four hours prior to administration the dose of medication
* Screening biosafety positive tests for the human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis Venereal Disease Research Laboratory (VDRL)
* Positive result in the abuse drugs screening tests, such as: amphetamines, benzodiazepines, cocaine, methamphetamines, morphine and tetrahydrocannabinoids
* Presence of alcohol in breath test
* Women pregnancy positive tests (qualitative and quantitative) at the screening and inclusion in each period
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Maximum Serum Concentration in Pre Dose Corrected Data (Cmax[aj]) of Levothyroxine (T4)
timeFrame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
measure: Area Under Serum Concentration-Time Curve From Time Zero to The Last Sampling Time in Pre Dose Corrected Data (AUC0-t [aj]) of Levothyroxine (T4)
timeFrame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
Secondary outcomes:
measure: Time to Reach Maximum Serum Concentration (Tmax) of Levothyroxine (T4)
timeFrame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
measure: Elimination Half-Life (t1/2) of Levothyroxine (T4)
timeFrame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
measure: Area Under The Curve of the Serum Concentration as a Function of Time, From Time Zero to The Last Sampling Time (AUC0-t) of Levothyroxine (T4)
timeFrame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
measure: Maximum Serum Concentration (Cmax) of Levothyroxine (T4)
timeFrame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.25, 3.5, 3.75, 4.0, 4.25, 4.5, 4.75, 5.0, 5.5, 6.0, 6.5, 8.0, 10.0, 12.0, 24.0, 36.0 and 48.0 hours post-dose
measure: Number of Participants With Clinically Significant Abnormalities in Physical Examination
timeFrame: Baseline up to Day 37
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: Baseline up to Day 37
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Baseline up to Day 37
measure: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
timeFrame: Baseline up to Day 37
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Day 51
Other outcomes:
Locations:
city: Morelia - Michoacan
country: Mexico
facility: Cecype, Fray Bernardino de Sahagún
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: