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This study will assess the food effect on bioavailability of Metformin/Gliclazide fixed dose combination tablet in fed and fasted state.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin-Gliclazide (fasted), Then Metformin-Gliclazide (fed) | Experimental | 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) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin/Gliclazide Fixed Combination | Drug | Participants will receive single oral dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting or fed state. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and 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). | 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 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide | 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) | 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 |
| Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide | Cmax is defined as the maximum observed plasma concentration. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide | Tmax is defined as the time to reach maximum plasma concentration. | 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 |
| Elimination Half Life (t1/2) of Metformin and Gliclazide |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CECYPE | Mexico City | Mexico |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
| |||||||||||||
| Treatment Period 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and 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). | 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. | Posted | Mean | Standard Deviation | Nanogram*hour per milliliter (ng*h/mL) | 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 |
|
Baseline up to Day 39
The safety population included all participants who received at least 1 dose of the study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin-Gliclazide (Fasted) | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated triglycerides | Investigations | MedDRA version 22 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 15, 2017 | Apr 18, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 12, 2018 | Apr 18, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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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. |
| 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 |
| Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide | Vz/f is defined as apparent volume of distribution during terminal phase after non-intravenous administration | 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 |
| Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma | CL/f is defined as apparent total clearance of the drug from plasma after oral administration. | 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 |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Baseline up to Day 39 |
| NOT COMPLETED |
|
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Metformin-Gliclazide (Fed) | 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. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide | 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) | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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 |
|
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide | Cmax is defined as the maximum observed plasma concentration. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
|
|
|
|
| Secondary | Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide | Tmax is defined as the time to reach maximum plasma concentration. | 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. | Posted | Mean | Standard Deviation | Hours | 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 |
|
|
|
| Secondary | Elimination Half Life (t1/2) of Metformin and Gliclazide | 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. | 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. | Posted | Mean | Standard Deviation | Hours | 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 |
|
|
|
| Secondary | Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide | Vz/f is defined as apparent volume of distribution during terminal phase after non-intravenous administration | 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. | Posted | Mean | Standard Deviation | Milliliter (mL) | 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 |
|
|
|
| Secondary | Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma | CL/f is defined as apparent total clearance of the drug from plasma after oral administration. | 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. | Posted | Mean | Standard Deviation | Liters | 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 |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | 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. | Posted | Count of Participants | Participants | Baseline up to Day 39 |
|
|
|
| 0 |
| 21 |
| 0 |
| 21 |
| 8 |
| 21 |
| EG001 | Metformin-Gliclazide (Fed) | 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. | 0 | 21 | 0 | 21 | 7 | 21 |
| Elevated total bilirubin | Investigations | MedDRA version 22 | Non-systematic Assessment |
|
| Elevated direct bilirubin | Investigations | MedDRA version 22 | Non-systematic Assessment |
|
| Elevated indirect bilirubin | Investigations | MedDRA version 22 | Non-systematic Assessment |
|
| High cholesterol | Investigations | MedDRA version 22 | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA version 22 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 22 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 22 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 22 | Non-systematic Assessment |
|
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Statistical Analysis for Gliclazide
| Ratio of mean values |
| 105.0818 |
| 2-Sided |
| 90 |
| 98.0047 |
| 112.6699 |
| Equivalence |
Bio-equivalence Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.0% - 125.0%. |
Statistical Analysis for Gliclazide
| Ratio of mean values |
| 105.4183 |
| 2-Sided |
| 90 |
| 94.5723 |
| 117.5081 |
| Equivalence |
Bio-equivalence Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.0% - 125.0%. |