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The purpose of this study is to assess bioequivalence between metformin hydrochloride (Glucophage® XR) manufactured in PT Merck Tbk, Indonesia (test drug) and metformin hydrochloride (Glucophage® XR) manufactured in Merck Santé, France (comparator drug) following single oral dose administration under fasting condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| First Glucophage XR (Test), Then Glucophage XR (Comparator) | Experimental | Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period. |
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| First Glucophage XR (Comparator), Then Glucophage XR (Test) | Experimental | Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glucophage XR (Test drug) | Drug | Participants received single oral dose of Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) under fasted conditions. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Metformin | The maximum plasma concentration of Metformin. | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin | Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration. | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Plasma Concentration Time Curve From Time Zero Extrapolated 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 (predose) to extrapolated infinite time (0-inf). | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | PT Merck Tbk, Indonesia, and affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PT Equilab International | Jakarta | 12430 | Indonesia |
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| ID | Title | Description |
|---|---|---|
| FG000 | First Glucophage XR (Test), Then Glucophage XR (Comparator) | Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period. |
| FG001 | First Glucophage XR (Comparator), Then Glucophage XR (Test) | Participants received single oral dose of 750 milligram (mg) Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) in treatment period 1 followed by single oral dose of 750 mg Glucophage® XR tablet manufactured by PT Merck Tbk, Jakarta, Indonesia (Test Drug) in treatment period 2 under fasting conditions. The two periods were separated by a 7-day wash-out period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Treatment Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia or Glucophage® XR 750 mg Tablet manufactured by Merck Santé, Semoy, France on Day 1 in either first treatment period or second treatment 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 | Maximum Observed Plasma Concentration (Cmax) of Metformin | The maximum plasma concentration of Metformin. | Pharmacokinetic (PK) analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment. | Posted | Mean | Standard Deviation | Nano-gram per milliliter (ng/mL) | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
|
Up to Day 51
The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment.
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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 | Glucophage XR (Test) | All participants who received Glucophage® XR 750 mg Tablet manufactured by PT Merck Tbk, Jakarta, Indonesia on Day 1 in either first treatment period or second treatment period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | WHO ART, Dec 2004 | 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 |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 6, 2018 | Sep 23, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | May 22, 2018 | Nov 4, 2019 | Prot_001.pdf |
| ID | Term |
|---|---|
| D008687 | Metformin |
| D004341 | Drug Evaluation |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D000076722 |
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| Glucophage XR (Comparator drug) | Drug | Participants received single oral dose of Glucophage® XR tablet manufactured by Merck Santé, Semoy, France (Comparator Drug) under fasted conditions. |
|
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| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | Time of the maximum drug concentration. | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
| Terminal Elimination Half-life in Plasma (t½) 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. | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non serious and serious TEAEs. | Up to Day 51 |
| NOT COMPLETED |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Glucophage XR (Comparator) |
All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin | Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration. | PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment. | Posted | Mean | Standard Deviation | Nanogram*hour per milliliter (ng*h/mL) | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
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|
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| Secondary | Area Under Plasma Concentration Time Curve From Time Zero Extrapolated 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 (predose) to extrapolated infinite time (0-inf). | PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment. | Posted | Mean | Standard Deviation | ng*h/mL | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
|
|
|
| Secondary | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | Time of the maximum drug concentration. | PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment. | Posted | Median | Full Range | Hours | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
|
|
|
| Secondary | Terminal Elimination Half-life in Plasma (t½) 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. | PK analysis set included all participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect the comparability of PK results, with adequate study medication compliance, and who have valid primary endpoints for both treatment. | Posted | Mean | Standard Deviation | Hours | Pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 24, and 32 hours post-dose on Day 1 |
|
|
|
| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. 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. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non serious and serious TEAEs. | The safety analysis set included all participants who have received at least one dose of the investigational product and have had one subsequent safety assessment. | Posted | Count of Participants | Participants | Up to Day 51 |
|
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|
| 0 |
| 47 |
| 0 |
| 47 |
| 5 |
| 47 |
| EG001 | Glucophage XR (Comparator) | All participants who received Glucophage® XR 750 mg Tablet (manufactured by Merck Santé, Semoy, France) on Day 1 in either first treatment period or second treatment period. | 0 | 46 | 0 | 46 | 9 | 46 |
| Stools loose | Gastrointestinal disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Headache | Nervous system disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Dermatitis venenata | Skin and subcutaneous tissue disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Conjunctival hyperaemia | Eye disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Urinary tract bleed microscopic | Renal and urinary disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Hemoglobin decreased | Blood and lymphatic system disorders | WHO ART, Dec 2004 | Non-systematic Assessment |
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| Drug Development |
| D008919 | Investigative Techniques |
| D005069 | Evaluation Studies as Topic |