Trial Outcomes & Findings for A Comparative Study of New Formulation and Approved Formulation for Levothyroxine in Healthy Volunteers (NCT NCT03979274)
NCT ID: NCT03979274
Last Updated: 2021-02-05
Results Overview
Cmax was obtained from the concentration time curve. Cmax\[aj\] was the maximum serum concentration in pre dose corrected data where pre dose corrected data was obtained by subtracting pre dose level of Levothyroxine (T4) from level of Levothyroxine (T4) after administration.
COMPLETED
PHASE1
44 participants
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
2021-02-05
Participant Flow
Participant milestones
| Measure |
Reference Eutirox®, Then Test Eutirox®
Participants received single oral dose of Reference Eutirox® 600 microgram (mcg) (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
|
Test Eutirox®, Then Reference Eutirox®
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
22
|
22
|
|
Treatment Period 1
COMPLETED
|
22
|
22
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
22
|
22
|
|
Treatment Period 2
COMPLETED
|
22
|
21
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Reference Eutirox®, Then Test Eutirox®
Participants received single oral dose of Reference Eutirox® 600 microgram (mcg) (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
|
Test Eutirox®, Then Reference Eutirox®
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 1 followed by single oral dosing of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in Treatment Period 2. A wash-out period of 35 days was maintained between the Treatment Periods 1 and 2.
|
|---|---|---|
|
Treatment Period 2
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
All Participants
n=44 Participants
All participants who received a single oral dose of Reference Eutirox® 600 mcg (200\*3 mcg) or a single oral dose of test Eutirox® 600 mcg (200\*3 mcg) in either Treatment Period 1 or 2.
|
|---|---|
|
Age, Continuous
|
25.93 years
STANDARD_DEVIATION 5.93 • n=44 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=44 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=44 Participants
|
PRIMARY outcome
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-dosePopulation: Pharmacokinetic (PK) analysis set included all randomized participants who received study medication in both treatment periods. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Cmax was obtained from the concentration time curve. Cmax\[aj\] was the maximum serum concentration in pre dose corrected data where pre dose corrected data was obtained by subtracting pre dose level of Levothyroxine (T4) from level of Levothyroxine (T4) after administration.
Outcome measures
| Measure |
Refernece Eutirox®
n=38 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=38 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Maximum Serum Concentration in Pre Dose Corrected Data (Cmax[aj]) of Levothyroxine (T4)
|
67.24 nanogram per milliliter (ng/mL)
Standard Deviation 15.77
|
66.44 nanogram per milliliter (ng/mL)
Standard Deviation 15.77
|
PRIMARY outcome
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-dosePopulation: PK analysis set included all randomized participants who received study medication in both treatment periods. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
AUC0-t was defined as area under the curve of the serum concentration as a function of time, from time 0 until the last sampling time by means of the trapezoidal rule. AUC0-t \[aj\] was the area under the serum concentration-time curve from time zero to the last sampling time in pre dose corrected data where pre dose corrected data was obtained by subtracting pre dose level of Levothyroxine (T4) from level of Levothyroxine (T4) after administration.
Outcome measures
| Measure |
Refernece Eutirox®
n=38 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=38 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
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)
|
1738.65 nanogram*hour per milliliter (ng*hr/mL)
Standard Deviation 438.93
|
1693.89 nanogram*hour per milliliter (ng*hr/mL)
Standard Deviation 389.50
|
SECONDARY outcome
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-dosePopulation: PK analysis set included all randomized participants who received study medication in both treatment periods.
Tmax was obtained directly from serum concentration-time curve.
Outcome measures
| Measure |
Refernece Eutirox®
n=43 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=43 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Time to Reach Maximum Serum Concentration (Tmax) of Levothyroxine (T4)
|
3.52 hour
Standard Deviation 1.19
|
3.50 hour
Standard Deviation 1.14
|
SECONDARY outcome
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-dosePopulation: PK analysis set included all randomized participants who received study medication in both treatment periods.
t1/2 was the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by elimination constant.
Outcome measures
| Measure |
Refernece Eutirox®
n=43 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=43 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Elimination Half-Life (t1/2) of Levothyroxine (T4)
|
186.40 hour
Standard Deviation 96.26
|
189.10 hour
Standard Deviation 102.07
|
SECONDARY outcome
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-dosePopulation: PK analysis set included all randomized participants who received study medication in both treatment periods.
Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ).
Outcome measures
| Measure |
Refernece Eutirox®
n=43 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=43 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
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)
|
5229.98 ng*hour/mL
Standard Deviation 562.73
|
5218.87 ng*hour/mL
Standard Deviation 587.42
|
SECONDARY outcome
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-dosePopulation: PK analysis set included all randomized participants who received study medication in both treatment periods.
Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Refernece Eutirox®
n=43 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=43 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Maximum Serum Concentration (Cmax) of Levothyroxine (T4)
|
139.80 ng/mL
Standard Deviation 16.16
|
139.17 ng/mL
Standard Deviation 19.24
|
SECONDARY outcome
Timeframe: Baseline up to Day 37Population: Safety analysis set included all randomized participants who received at least one dose of study medication.
Physical examination included assessments of the general appearance, skin and mucosa, superficial lymph nodes, head and neck, chest, abdomen, musculoskeletal, and neurological systems. Number of participants with clinically significant abnormalities in physical examination findings were reported. Investigator decided clinical significance.
Outcome measures
| Measure |
Refernece Eutirox®
n=44 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=44 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Physical Examination
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 37Population: Safety analysis set included all randomized participants who received at least one dose of study medication.
Vital sign assessment included blood pressure, pulse rate, body temperature and respiration. Number of participants with clinically significant abnormalities in vital signs were reported. Investigator decided clinical significance.
Outcome measures
| Measure |
Refernece Eutirox®
n=44 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=44 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Vital Signs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 37Population: Safety analysis set included all randomized participants who received at least one dose of study medication.
The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory parameters were reported. Investigator decided clinical significance.
Outcome measures
| Measure |
Refernece Eutirox®
n=44 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=44 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 37Population: Safety analysis set included all randomized participants who received at least one dose of study medication.
The ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in ECG were reported. Investigator decided clinical significance.
Outcome measures
| Measure |
Refernece Eutirox®
n=44 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=44 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 51Population: Safety analysis set included all randomized participants who received at least one dose of study medication.
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. Number of participants with adverse events were reported.
Outcome measures
| Measure |
Refernece Eutirox®
n=44 Participants
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=44 Participants
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
|
0 Participants
|
4 Participants
|
Adverse Events
Reference Eutirox®
Test Eutirox®
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Reference Eutirox®
n=44 participants at risk
Participants received single oral dose of Reference Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
Test Eutirox®
n=44 participants at risk
Participants received single oral dose of Test Eutirox® 600 mcg (3 tablets of 200 mcg) in either Treatment Period 1 or 2 under fasting conditions.
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
0.00%
0/44 • Baseline up to Day 51
|
2.3%
1/44 • Baseline up to Day 51
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/44 • Baseline up to Day 51
|
2.3%
1/44 • Baseline up to Day 51
|
|
Investigations
Elevated Alanine Aminotransferase
|
0.00%
0/44 • Baseline up to Day 51
|
4.5%
2/44 • Baseline up to Day 51
|
|
Investigations
Elevated Aspartate Aminotransferase
|
0.00%
0/44 • Baseline up to Day 51
|
4.5%
2/44 • Baseline up to Day 51
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place