Trial Outcomes & Findings for Bioequivalence of Two Formulations of Levothyroxine Sodium 200 Micrograms (mcg) Under Tablet Form (NCT NCT04037748)
NCT ID: NCT04037748
Last Updated: 2020-09-29
Results Overview
Cmax was obtained from plasma concentration time curve. Maximum plasmatic concentration observed adjusted by basal level correction was reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
72 participants
Primary outcome timeframe
Pre-dose, 24, 36, 48 and 72 hours post-dose
Results posted on
2020-09-29
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
36
|
36
|
|
Treatment Period 1
COMPLETED
|
28
|
30
|
|
Treatment Period 1
NOT COMPLETED
|
8
|
6
|
|
Treatment Period 2
STARTED
|
28
|
30
|
|
Treatment Period 2
COMPLETED
|
26
|
29
|
|
Treatment Period 2
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Treatment Period 1
Withdrawal by Subject
|
3
|
0
|
|
Treatment Period 1
Adverse Event
|
1
|
1
|
|
Treatment Period 1
Protocol Violation
|
4
|
5
|
|
Treatment Period 2
Adverse Event
|
0
|
1
|
|
Treatment Period 2
Protocol Violation
|
2
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
First Puran T4®, Then Eutirox®
n=36 Participants
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®
n=36 Participants
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.
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.0 Years
STANDARD_DEVIATION 8.7 • n=36 Participants
|
35.9 Years
STANDARD_DEVIATION 9.3 • n=36 Participants
|
35.5 Years
STANDARD_DEVIATION 8.9 • n=72 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=36 Participants
|
18 Participants
n=36 Participants
|
36 Participants
n=72 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=36 Participants
|
18 Participants
n=36 Participants
|
36 Participants
n=72 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: Pre-dose, 24, 36, 48 and 72 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included all participants who completed both periods and had valid PK parameters in both.
Cmax was obtained from plasma concentration time curve. Maximum plasmatic concentration observed adjusted by basal level correction was reported.
Outcome measures
| Measure |
Puran T4®
n=55 Participants
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®
n=55 Participants
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.
|
|---|---|---|
|
Baseline Corrected Maximum Observed Plasma Concentration (Cmax[Adj]) of Levothyroxine Sodium
|
67.258 Nanogram per milliliter (ng/mL)
Standard Deviation 19.654
|
60.552 Nanogram per milliliter (ng/mL)
Standard Deviation 13.61
|
PRIMARY outcome
Timeframe: Pre-dose, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set included all participants who completed both periods and had valid PK parameters in both.
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.
Outcome measures
| Measure |
Puran T4®
n=55 Participants
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®
n=55 Participants
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.
|
|---|---|---|
|
Baseline Corrected Area Under The Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC0-72 [Adj]) of Levothyroxine Sodium
|
2682.371 Hour* ng/mL
Standard Deviation 795.263
|
2516.055 Hour* ng/mL
Standard Deviation 716.575
|
SECONDARY outcome
Timeframe: Pre-dose, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set included all participants who completed both periods and had valid PK parameters in both.
Tmax was obtained from plasma concentration time curve.
Outcome measures
| Measure |
Puran T4®
n=55 Participants
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®
n=55 Participants
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.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Levothyroxine Sodium
|
3.50 Hours
Interval 1.0 to 6.0
|
4.00 Hours
Interval 1.5 to 8.0
|
SECONDARY outcome
Timeframe: Pre-dose, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set included all participants who completed both periods and had valid PK parameters in both.
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.
Outcome measures
| Measure |
Puran T4®
n=55 Participants
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®
n=55 Participants
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.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to 72 Hours (AUC 0-72) of Levothyroxine Sodium
|
7204.615 Hour* ng/mL
Standard Deviation 1337.674
|
7004.507 Hour* ng/mL
Standard Deviation 1154.596
|
SECONDARY outcome
Timeframe: Pre-dose, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set included all participants who completed both periods and had valid PK parameters in both.
Cmax was obtained from plasma concentration time curve.
Outcome measures
| Measure |
Puran T4®
n=55 Participants
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®
n=55 Participants
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.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Levothyroxine Sodium
|
130.069 ng/mL
Standard Deviation 25.464
|
122.895 ng/mL
Standard Deviation 18.957
|
Adverse Events
Puran T4
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Eutirox®
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Puran T4
n=72 participants at risk
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®
n=72 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
1.4%
1/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
1.4%
1/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhea
|
1.4%
1/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
1.4%
1/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
4.2%
3/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
|
Nervous system disorders
Lipothymia
|
0.00%
0/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
1.4%
1/72 • Up to 79 Days; Participants were assessed for adverse events for the entire study.
Safety analysis set included all randomized participants who received one dose of study drug.
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place