Trial Outcomes & Findings for A Study to Assess the Food Effect on Bioavailability of Metformin/Gliclazide in Healthy Participants (NCT NCT03467971)
NCT ID: NCT03467971
Last Updated: 2019-07-08
Results Overview
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).
COMPLETED
PHASE1
21 participants
Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
2019-07-08
Participant Flow
Participant milestones
| Measure |
Metformin-Gliclazide (Fasted), Then Metformin-Gliclazide (Fed)
Participants received single dose of Metformin 1000 milligram (mg) and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 2. Each treatment period was separated by a 14-day wash-out period.
|
Metformin-Gliclazide (Fed), Then Metformin-Gliclazide (Fasted)
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 2. Each treatment period will be separated by a 14-day wash-out period.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
10
|
11
|
|
Treatment Period 1
COMPLETED
|
10
|
11
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
10
|
11
|
|
Treatment Period 2
COMPLETED
|
10
|
10
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Metformin-Gliclazide (Fasted), Then Metformin-Gliclazide (Fed)
Participants received single dose of Metformin 1000 milligram (mg) and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 2. Each treatment period was separated by a 14-day wash-out period.
|
Metformin-Gliclazide (Fed), Then Metformin-Gliclazide (Fasted)
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 2. Each treatment period will be separated by a 14-day wash-out period.
|
|---|---|---|
|
Treatment Period 2
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Study to Assess the Food Effect on Bioavailability of Metformin/Gliclazide in Healthy Participants
Baseline characteristics by cohort
| Measure |
Metformin-Gliclazide (Fasted), Then Metformin-Gliclazide (Fed)
n=10 Participants
Participants received single dose of Metformin 1000 milligram (mg) and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 2. Each treatment period was separated by a 14-day wash-out period.
|
Metformin-Gliclazide (Fed), Then Metformin-Gliclazide (Fasted)
n=11 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 2. Each treatment period will be separated by a 14-day wash-out period.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.2 Years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
32.5 Years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
34.7 Years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: The Pharmacokinetics (PK) analysis set included all participants who completed the study with adequate study 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 (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and Gliclazide
Metformin
|
4974.2507 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 1599.3290
|
8556.7752 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 2544.6658
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and Gliclazide
Gliclazide
|
21192.1682 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 9220.3044
|
21815.4021 Nanogram*hour per milliliter (ng*h/mL)
Standard Deviation 8369.0107
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: PK analysis set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
AUC (0-t) is defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Outcome measures
| Measure |
Metformin-Gliclazide (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide
Metformin
|
4722.4546 ng*h/mL
Standard Deviation 1598.1082
|
8298.5628 ng*h/mL
Standard Deviation 2422.9059
|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide
Gliclazide
|
20348.8381 ng*h/mL
Standard Deviation 9154.5509
|
20997.1704 ng*h/mL
Standard Deviation 8244.2743
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: PK analysis set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Cmax is defined as the maximum observed plasma concentration.
Outcome measures
| Measure |
Metformin-Gliclazide (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide
Metformin
|
717.5017 ng/mL
Standard Deviation 304.8105
|
870.7288 ng/mL
Standard Deviation 272.6886
|
|
Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide
Gliclazide
|
968.0305 ng/mL
Standard Deviation 261.8362
|
1013.9753 ng/mL
Standard Deviation 243.1601
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: The PK analysis set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Tmax is defined as the time to reach maximum plasma concentration.
Outcome measures
| Measure |
Metformin-Gliclazide (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide
Metformin
|
3.6698 Hours
Standard Deviation 0.6600
|
7.2389 Hours
Standard Deviation 0.7693
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide
Gliclazide
|
6.5254 Hours
Standard Deviation 1.7474
|
8.5238 Hours
Standard Deviation 2.1822
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: The PK analysis set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Elimination Half Life (t1/2) is 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 (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Elimination Half Life (t1/2) of Metformin and Gliclazide
Metformin
|
6.2547 Hours
Standard Deviation 2.9771
|
7.4892 Hours
Standard Deviation 8.7276
|
|
Elimination Half Life (t1/2) of Metformin and Gliclazide
Gliclazide
|
16.6222 Hours
Standard Deviation 6.2627
|
17.1044 Hours
Standard Deviation 7.5000
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: The PK analysis set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
Vz/f is defined as apparent volume of distribution during terminal phase after non-intravenous administration
Outcome measures
| Measure |
Metformin-Gliclazide (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide
Gliclazide
|
35189.3864 Milliliter (mL)
Standard Deviation 8855.9499
|
33813.7843 Milliliter (mL)
Standard Deviation 6970.7706
|
|
Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide
Metformin
|
2003389.9474 Milliliter (mL)
Standard Deviation 1157828.4547
|
1200933.2647 Milliliter (mL)
Standard Deviation 949837.2019
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dosePopulation: The PK analysis set included all participants who completed the study with adequate study medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results.
CL/f is defined as apparent total clearance of the drug from plasma after oral administration.
Outcome measures
| Measure |
Metformin-Gliclazide (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma
Metformin
|
226.79 Liters
Standard Deviation 88.58
|
125.93 Liters
Standard Deviation 33.92
|
|
Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma
Glilclazide
|
1.63 Liters
Standard Deviation 0.57
|
1.55 Liters
Standard Deviation 0.52
|
SECONDARY outcome
Timeframe: Baseline up to Day 39Population: The safety population included all participants who received at least 1 dose of the study treatment in either treatment period 1 or treatment period 2.
Adverse event(AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Metformin-Gliclazide (Fasted)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 Participants
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse Events
|
8 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Serious Adverse Events (SAEs)
|
0 Participants
|
0 Participants
|
Adverse Events
Metformin-Gliclazide (Fasted)
Metformin-Gliclazide (Fed)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin-Gliclazide (Fasted)
n=21 participants at risk
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 or in treatment period 2.
|
Metformin-Gliclazide (Fed)
n=21 participants at risk
Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 or in treatment period 2.
|
|---|---|---|
|
Investigations
Elevated triglycerides
|
9.5%
2/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
14.3%
3/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Investigations
Elevated total bilirubin
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Investigations
Elevated direct bilirubin
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Investigations
Elevated indirect bilirubin
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Investigations
High cholesterol
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
14.3%
3/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Nervous system disorders
Headache
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.8%
1/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
0.00%
0/21 • Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place