Trial Outcomes & Findings for Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants (NCT NCT03467945)
NCT ID: NCT03467945
Last Updated: 2019-07-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Results posted on
2019-07-16
Participant Flow
Participant milestones
| Measure |
Treatment Sequence 1
Participants received single oral dose of metformin 1000 milligram (mg) and gliclazide 30 mg fixed combination tablet in treatment period 1 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg in treatment period 3 and then a single oral dose of gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 2
Participants received concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 1 followed by single oral dose of gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 3 and then single oral dose of metformin 1000 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 3
Participants received single oral dose of metformin 1000 mg in treatment period 1 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 2 followed by single oral dose of gliclazide 30 mg in treatment period 3 and then concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 4
Participants received single oral dose of gliclazide 30 mg in treatment period 1 followed by single oral dose of metformin 1000 mg in treatment period 2 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 3 and then single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
10
|
10
|
10
|
10
|
|
Treatment Period 1
COMPLETED
|
10
|
10
|
10
|
10
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
10
|
10
|
10
|
10
|
|
Treatment Period 2
COMPLETED
|
10
|
9
|
10
|
10
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Treatment Period 3
STARTED
|
10
|
9
|
10
|
10
|
|
Treatment Period 3
COMPLETED
|
9
|
9
|
8
|
9
|
|
Treatment Period 3
NOT COMPLETED
|
1
|
0
|
2
|
1
|
|
Treatment Period 4
STARTED
|
9
|
9
|
8
|
9
|
|
Treatment Period 4
COMPLETED
|
9
|
9
|
8
|
9
|
|
Treatment Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence 1
Participants received single oral dose of metformin 1000 milligram (mg) and gliclazide 30 mg fixed combination tablet in treatment period 1 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg in treatment period 3 and then a single oral dose of gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 2
Participants received concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 1 followed by single oral dose of gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 3 and then single oral dose of metformin 1000 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 3
Participants received single oral dose of metformin 1000 mg in treatment period 1 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 2 followed by single oral dose of gliclazide 30 mg in treatment period 3 and then concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 4
Participants received single oral dose of gliclazide 30 mg in treatment period 1 followed by single oral dose of metformin 1000 mg in treatment period 2 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 3 and then single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
|---|---|---|---|---|
|
Treatment Period 2
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Treatment Period 3
Withdrawal by Subject
|
1
|
0
|
2
|
1
|
Baseline Characteristics
Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants
Baseline characteristics by cohort
| Measure |
Treatment Sequence 1
n=10 Participants
Participants received single oral dose of metformin 1000 milligram (mg) and gliclazide 30 mg fixed combination tablet in treatment period 1 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg in treatment period 3 and then a single oral dose of gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 2
n=10 Participants
Participants received concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 1 followed by single oral dose of gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 3 and then single oral dose of metformin 1000 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 3
n=10 Participants
Participants received single oral dose of metformin 1000 mg in treatment period 1 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 2 followed by single oral dose of gliclazide 30 mg in treatment period 3 and then concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Treatment Sequence 4
n=10 Participants
Participants received single oral dose of gliclazide 30 mg in treatment period 1 followed by single oral dose of metformin 1000 mg in treatment period 2 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 3 and then single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 4. Each treatment period was separated by a 14-day wash-out period.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
22.8 Years
STANDARD_DEVIATION 9.8 • n=99 Participants
|
23.9 Years
STANDARD_DEVIATION 3.7 • n=107 Participants
|
31.5 Years
STANDARD_DEVIATION 8.3 • n=206 Participants
|
25.7 Years
STANDARD_DEVIATION 5.2 • n=7 Participants
|
27.3 Years
STANDARD_DEVIATION 7.5 • n=31 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
17 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
23 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
40 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The Pharmacokinetic (PK) analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
|
5033.8718 nanogram*hour per milliliter (ng*h/ml)
Standard Deviation 1475.3418
|
6142.2821 nanogram*hour per milliliter (ng*h/ml)
Standard Deviation 1848.4857
|
6090.7932 nanogram*hour per milliliter (ng*h/ml)
Standard Deviation 1543.6463
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide
|
20707.7394 ng.h/ml
Standard Deviation 8267.0653
|
20280.3103 ng.h/ml
Standard Deviation 8219.1520
|
21205.2514 ng.h/ml
Standard Deviation 7638.0877
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Metformin
|
806.3895 nanogram per milliliter (ng/ml)
Standard Deviation 279.5063
|
1011.3941 nanogram per milliliter (ng/ml)
Standard Deviation 309.8136
|
977.2693 nanogram per milliliter (ng/ml)
Standard Deviation 262.4312
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Gliclazide
|
972.168 ng/ml
Standard Deviation 312.7305
|
892.6201 ng/ml
Standard Deviation 259.7459
|
836.7239 ng/ml
Standard Deviation 251.6451
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
AUC (0-inf) is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin
|
5313.3897 ng*h/ml
Standard Deviation 1549.2688
|
6388.9849 ng*h/ml
Standard Deviation 1857.6205
|
6341.5658 ng*h/ml
Standard Deviation 1560.7170
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
AUC (0-inf) is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide
|
21495.2343 ng*h/ml
Standard Deviation 8358.3373
|
21120.6761 ng*h/ml
Standard Deviation 8270.5092
|
22136.9988 ng*h/ml
Standard Deviation 7687.4829
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution (Vz/f) of Metformin
|
1893618.4672 Milliliter
Standard Deviation 1346880.1198
|
1414424.1926 Milliliter
Standard Deviation 643556.2088
|
1489164.0229 Milliliter
Standard Deviation 818767.0681
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution (Vz/f) of Gliclazide
|
31636.8920 Milliliter
Standard Deviation 7584.1651
|
32601.0115 Milliliter
Standard Deviation 7057.8050
|
31413.9679 Milliliter
Standard Deviation 6422.4920
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Elimination Half Life (t1/2) of Metformin
|
6.7151 Hours
Standard Deviation 5.1372
|
5.9796 Hours
Standard Deviation 2.8442
|
6.3048 Hours
Standard Deviation 3.7114
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Elimination Half Life (t1/2) of Gliclazide
|
15.3086 Hours
Standard Deviation 6.0231
|
15.4587 Hours
Standard Deviation 5.6007
|
15.6222 Hours
Standard Deviation 5.2904
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Apparent Total Body Clearance (CL/f) of Metformin
|
207132.8293 Milliliter per Hour (mL/ h)
Standard Deviation 70959.4296
|
170273.4024 Milliliter per Hour (mL/ h)
Standard Deviation 51108.0288
|
167260.5841 Milliliter per Hour (mL/ h)
Standard Deviation 39170.7306
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Apparent Total Body Clearance (CL/f) of Gliclazide
|
1572.5246 mL/h
Standard Deviation 516.3724
|
1606.8952 mL/h
Standard Deviation 569.4811
|
1498.9932 mL/h
Standard Deviation 463.2158
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
MRT is the average time that the molecules introduced into the body stays in the body.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Median Residence Time (MRT) for Metformin
|
8.3952 Hours
Standard Deviation 3.0758
|
7.5836 Hours
Standard Deviation 1.6807
|
7.7636 Hours
Standard Deviation 2.0658
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dosePopulation: The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
MRT is the average time that the molecules introduced into the body stays in the body.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Median Residence Time (MRT) for Gliclazide
|
23.0593 Hours
Standard Deviation 7.8010
|
24.4927 Hours
Standard Deviation 7.7484
|
25.8590 Hours
Standard Deviation 7.5834
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Day 72Population: The safety population included all participants who received at least 1 dose of the trial treatment.
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 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. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Metformin-Gliclazide Combination
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 Participants
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 Participants
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
n=35 Participants
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
9 Participants
|
6 Participants
|
7 Participants
|
8 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Metformin-Gliclazide Combination
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Metformin and Gliclazide Separately
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Metformin
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Gliclazide
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin-Gliclazide Combination
n=35 participants at risk
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4.
|
Metformin and Gliclazide Separately
n=35 participants at risk
Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4.
|
Metformin
n=35 participants at risk
Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4.
|
Gliclazide
n=35 participants at risk
Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4.
|
|---|---|---|---|---|
|
Investigations
Elevated triglycerides
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
8.6%
3/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
5.7%
2/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Investigations
High cholesterol
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Investigations
Elevated alanine aminostrasferase
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
11.4%
4/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Investigations
Elevated aspartate aminotrasferase
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
14.3%
5/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Blood and lymphatic system disorders
Anemia
|
14.3%
5/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
5.7%
2/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
14.3%
5/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
20.0%
7/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Nervous system disorders
Vasovagal reaction
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Gastrointestinal disorders
Infectious gastroenteritis
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Injury, poisoning and procedural complications
Wound in the left submaxillary region
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Infections and infestations
Urinary infection
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
|
Infections and infestations
Urethritis
|
2.9%
1/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
5.7%
2/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
0.00%
0/35 • Baseline up to Day 72
The safety population included all participants who received at least 1 dose of the trial treatment.
|
Additional Information
Communication Center
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