Healthy
Conditions
Keywords
Metformin, Gliclazide, Bioequivalence, Drug-drug Interaction, Pharmacokinetics
Brief summary
This study investigated the bioequivalence and drug-drug interaction of Metformin/Gliclazide fixed combination tablet compared to co-administration of individual tablets of Metformin and Gliclazide.
Interventions
Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.
DRUGMetformin
Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.
DRUGGliclazide
Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants has given written informed consent before any study-related activities were carried out * Ethnic origin: Mexicans * Weight between 55 and 95 kilogram (kg) * Body mass index between 18.5 and 27 kilogram per meter square (kg/m\^2) * Not smoking more than 5 cigarettes or 1 cigar or 1 pipe per day (or non smokers) * Good physical and mental health status * Vital signs (blood pressure and pulse) in supine position within the normal range or showing no clinically relevant deviation as judged by the Investigator * Electrocardiogram recording (12-lead) without signs of clinically relevant pathology in particular QTc (Bazett) \<450 milliseconds (ms) * All values for biochemistry and hematology tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the Investigator * All women of childbearing potential (WOCBP) were not nursing, were not pregnant, and were using highly effective methods of birth control for a period of at least one month before and after dosing * All women of childbearing potential must have negative tests for pregnancy at screening, and at day -1 for each treatment period and at end of trial (EOT) * Negative screen for alcohol and drugs of abuse at Screening and on each admission * Negative screen for Hepatitis B surface (HBs) antigens, Hepatitis C Virus (HCV) antibodies, Hepatitis A Virus (HAV) antibodies and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participation in a clinical trial within 90 days prior to first drug administration * Participants who have donated more than 500 milliliter (mL) of blood or who have lost significantly (more than 450 mL) blood within 90 days prior to first drug of administration * Any surgical or medical condition, constitutes a risk or a contraindication for the participation of the participant in the study or that could interfere with the study objectives, conduct or evaluation * History of surgery of the gastrointestinal tract * Allergy * Receipt of any prescription or non-prescription medication within 2 weeks before the first study drug administration * Renal failure or renal dysfunction (creatinine clearance less than \[\<\] 80 mL/minute) as assessed by using the estimated measure with the Cockcroft-Gault formula * Known lack of participant compliance or inability to communicate or cooperate with the Investigator * Considerable diet deviations from normal nutritional patterns * Consumption of large quantities of methylxanthine-containing beverages (more than 600 milligram \[mg\] caffeine / day: one cup \[240 mL\] of coffee contains approx. 100 mg of caffeine, one cup of tea approximately 30 mg and one glass of cola approximately 20 mg caffeine) * Consumption of grapefruit, orange, cranberry or juices of these fruits, 14 days prior to drug administration and during the study * Legal incapacity or limited legal capacity * Participants kept in detention * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin | 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 | — |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide | 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 | — |
| Maximum Observed Plasma Concentration (Cmax) of Metformin | 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 | — |
| Maximum Observed Plasma Concentration (Cmax) of Gliclazide | 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 | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin | 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 | 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). |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Residence Time (MRT) for Metformin | 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 | MRT is the average time that the molecules introduced into the body stays in the body. |
| Apparent Volume of Distribution (Vz/f) of Metformin | 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 | Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to Day 72 | 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. |
| Median Residence Time (MRT) for Gliclazide | 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 | MRT is the average time that the molecules introduced into the body stays in the body. |
| Apparent Volume of Distribution (Vz/f) of Gliclazide | 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 | Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration. |
| Elimination Half Life (t1/2) of Metformin | 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 | 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. |
| Elimination Half Life (t1/2) of Gliclazide | 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 | 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. |
| Apparent Total Body Clearance (CL/f) of Metformin | 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 | CL/f was defined as apparent total clearance of the drug from plasma after oral administration. |
| Apparent Total Body Clearance (CL/f) of Gliclazide | 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 | CL/f was defined as apparent total clearance of the drug from plasma after oral administration. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 10 |
| 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. | 10 |
| 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. | 10 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Treatment Period 3 | Withdrawal by Subject | 1 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence 1 | Treatment Sequence 2 | Treatment Sequence 3 | Treatment Sequence 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 22.8 Years STANDARD_DEVIATION 9.8 | 23.9 Years STANDARD_DEVIATION 3.7 | 31.5 Years STANDARD_DEVIATION 8.3 | 25.7 Years STANDARD_DEVIATION 5.2 | 27.3 Years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 10 Participants | 10 Participants | 10 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 3 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 7 Participants | 5 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 9 / 35 | 6 / 35 | 7 / 35 | 8 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | 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 |
| Metformin and Gliclazide Separately | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide | 21120.6761 ng*h/ml | Standard Deviation 8270.5092 |
| Metformin | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide | 22136.9988 ng*h/ml | Standard Deviation 7687.4829 |
90% CI: [101.49, 110.533]
90% CI: [92.1443, 100.3546]
90% CI: [97.5947, 106.2906]
Primary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | 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 |
| Metformin and Gliclazide Separately | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin | 6388.9849 ng*h/ml | Standard Deviation 1857.6205 |
| Metformin | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin | 6341.5658 ng*h/ml | Standard Deviation 1560.717 |
90% CI: [76.5513, 89.1314]
90% CI: [97.8819, 106.9028]
90% CI: [74.8823, 87.6417]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | 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 |
| Metformin and Gliclazide Separately | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide | 20280.3103 ng.h/ml | Standard Deviation 8219.152 |
| Metformin | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide | 21205.2514 ng.h/ml | Standard Deviation 7638.0877 |
90% CI: [97.8819, 106.9028]
90% CI: [101.1665, 110.49]
90% CI: [92.5812, 101.1135]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | 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 |
| Metformin and Gliclazide Separately | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin | 6142.2821 nanogram*hour per milliliter (ng*h/ml) | Standard Deviation 1848.4857 |
| Metformin | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin | 6090.7932 nanogram*hour per milliliter (ng*h/ml) | Standard Deviation 1543.6463 |
90% CI: [75.2805, 88.1079]
90% CI: [97.8819, 106.9028]
90% CI: [74.8823, 87.6417]
Primary
Maximum Observed Plasma Concentration (Cmax) of Gliclazide
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Maximum Observed Plasma Concentration (Cmax) of Gliclazide | 972.168 ng/ml | Standard Deviation 312.7305 |
| Metformin and Gliclazide Separately | Maximum Observed Plasma Concentration (Cmax) of Gliclazide | 892.6201 ng/ml | Standard Deviation 259.7459 |
| Metformin | Maximum Observed Plasma Concentration (Cmax) of Gliclazide | 836.7239 ng/ml | Standard Deviation 251.6451 |
90% CI: [102.237, 114.2609]
90% CI: [88.6166, 99.0386]
90% CI: [109.131, 121.9658]
Primary
Maximum Observed Plasma Concentration (Cmax) of Metformin
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Maximum Observed Plasma Concentration (Cmax) of Metformin | 806.3895 nanogram per milliliter (ng/ml) | Standard Deviation 279.5063 |
| Metformin and Gliclazide Separately | Maximum Observed Plasma Concentration (Cmax) of Metformin | 1011.3941 nanogram per milliliter (ng/ml) | Standard Deviation 309.8136 |
| Metformin | Maximum Observed Plasma Concentration (Cmax) of Metformin | 977.2693 nanogram per milliliter (ng/ml) | Standard Deviation 262.4312 |
90% CI: [70.383, 85.7606]
90% CI: [102.237, 114.2609]
90% CI: [71.9633, 87.6861]
Secondary
Apparent Total Body Clearance (CL/f) of Gliclazide
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Apparent Total Body Clearance (CL/f) of Gliclazide | 1572.5246 mL/h | Standard Deviation 516.3724 |
| Metformin and Gliclazide Separately | Apparent Total Body Clearance (CL/f) of Gliclazide | 1606.8952 mL/h | Standard Deviation 569.4811 |
| Metformin | Apparent Total Body Clearance (CL/f) of Gliclazide | 1498.9932 mL/h | Standard Deviation 463.2158 |
Secondary
Apparent Total Body Clearance (CL/f) of Metformin
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Apparent Total Body Clearance (CL/f) of Metformin | 207132.8293 Milliliter per Hour (mL/ h) | Standard Deviation 70959.4296 |
| Metformin and Gliclazide Separately | Apparent Total Body Clearance (CL/f) of Metformin | 170273.4024 Milliliter per Hour (mL/ h) | Standard Deviation 51108.0288 |
| Metformin | Apparent Total Body Clearance (CL/f) of Metformin | 167260.5841 Milliliter per Hour (mL/ h) | Standard Deviation 39170.7306 |
Secondary
Apparent Volume of Distribution (Vz/f) of Gliclazide
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Apparent Volume of Distribution (Vz/f) of Gliclazide | 31636.8920 Milliliter | Standard Deviation 7584.1651 |
| Metformin and Gliclazide Separately | Apparent Volume of Distribution (Vz/f) of Gliclazide | 32601.0115 Milliliter | Standard Deviation 7057.805 |
| Metformin | Apparent Volume of Distribution (Vz/f) of Gliclazide | 31413.9679 Milliliter | Standard Deviation 6422.492 |
Secondary
Apparent Volume of Distribution (Vz/f) of Metformin
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Apparent Volume of Distribution (Vz/f) of Metformin | 1893618.4672 Milliliter | Standard Deviation 1346880.1198 |
| Metformin and Gliclazide Separately | Apparent Volume of Distribution (Vz/f) of Metformin | 1414424.1926 Milliliter | Standard Deviation 643556.2088 |
| Metformin | Apparent Volume of Distribution (Vz/f) of Metformin | 1489164.0229 Milliliter | Standard Deviation 818767.0681 |
Secondary
Elimination Half Life (t1/2) of Gliclazide
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Elimination Half Life (t1/2) of Gliclazide | 15.3086 Hours | Standard Deviation 6.0231 |
| Metformin and Gliclazide Separately | Elimination Half Life (t1/2) of Gliclazide | 15.4587 Hours | Standard Deviation 5.6007 |
| Metformin | Elimination Half Life (t1/2) of Gliclazide | 15.6222 Hours | Standard Deviation 5.2904 |
Secondary
Elimination Half Life (t1/2) of Metformin
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Elimination Half Life (t1/2) of Metformin | 6.7151 Hours | Standard Deviation 5.1372 |
| Metformin and Gliclazide Separately | Elimination Half Life (t1/2) of Metformin | 5.9796 Hours | Standard Deviation 2.8442 |
| Metformin | Elimination Half Life (t1/2) of Metformin | 6.3048 Hours | Standard Deviation 3.7114 |
Secondary
Median Residence Time (MRT) for Gliclazide
MRT is the average time that the molecules introduced into the body stays in the body.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Median Residence Time (MRT) for Gliclazide | 23.0593 Hours | Standard Deviation 7.801 |
| Metformin and Gliclazide Separately | Median Residence Time (MRT) for Gliclazide | 24.4927 Hours | Standard Deviation 7.7484 |
| Metformin | Median Residence Time (MRT) for Gliclazide | 25.8590 Hours | Standard Deviation 7.5834 |
Secondary
Median Residence Time (MRT) for Metformin
MRT is the average time that the molecules introduced into the body stays in the body.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin-Gliclazide Combination | Median Residence Time (MRT) for Metformin | 8.3952 Hours | Standard Deviation 3.0758 |
| Metformin and Gliclazide Separately | Median Residence Time (MRT) for Metformin | 7.5836 Hours | Standard Deviation 1.6807 |
| Metformin | Median Residence Time (MRT) for Metformin | 7.7636 Hours | Standard Deviation 2.0658 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: Baseline up to Day 72
Population: The safety population included all participants who received at least 1 dose of the trial treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metformin-Gliclazide Combination | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 9 Participants |
| Metformin-Gliclazide Combination | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Metformin and Gliclazide Separately | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Metformin and Gliclazide Separately | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 6 Participants |
| Metformin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Metformin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Gliclazide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 8 Participants |
| Gliclazide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |