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The study will assess the bioequivalence between single doses of GXR manufactured in Merck Nantong China (test drug) and GXR manufactured in Merck Darmstadt Germany (reference drug) under fed and fasted state in healthy participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| First Test GXR (Fasting), Then Reference GXR (Fasting) | Experimental | Participants received a single oral dose of 500 milligrams (mg) of test GXR tablet (Merck Nantong/China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR (Merck Darmstadt/Germany) on Day 8 in treatment period 2 under fasting conditions. There was a wash-out period of 7 days between each treatment period. |
|
| First Reference GXR (Fasting), Then Test GXR (Fasting) | Experimental | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/Germany) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR (Merck Nantong/China) on Day 8 in treatment period 2 under fasting conditions. There was a wash-out period of 7 days between each treatment period. |
|
| First Test GXR (Fed), Then Reference GXR (Fed) | Experimental | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR (Merck Darmstadt/Germany) on Day 8 in treatment period 2 under fed conditions. There was a wash-out period of 7 days between each treatment period. |
|
| First Reference GXR (Fed), Then Test GXR (Fed) | Experimental | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/Germany) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR (Merck Nantong/China) on Day 8 in treatment period 2 under fed conditions. There was a wash-out period of 7 days between each treatment period. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Test GXR | Drug | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2). |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin | Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Maximum Observed Plasma Concentration (Cmax) of Metformin | Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach Maximum Plasma Concentration of Metformin | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Pharmaceutical Manufacturing (Jiangsu) Co., Ltd., an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xuanwu Hospital Capital Medical University | Beijing | China |
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| ID | Title | Description |
|---|---|---|
| FG000 | First Test GXR (Fasting), Then Reference GXR (Fasting) | Participants received a single oral dose of 500 milligrams (mg) of test GXR tablet (Merck Nantong, China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR (Merck Darmstadt, Germany) on Day 8 in treatment period 2 under fasting conditions. There was a wash-out period of 7 days between each treatment period. |
| FG001 | First Reference GXR (Fasting), Then Test GXR (Fasting) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt, Germany) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR (Merck Nantong, China) on Day 8 in treatment period 2 under fasting conditions. There was a wash-out period of 7 days between each treatment period. |
| FG002 | First Test GXR (Fed), Then Reference GXR (Fed) | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong, China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR (Merck Darmstadt, Germany) on Day 8 in treatment period 2 under fed conditions. There was a wash-out period of 7 days between each treatment period. |
| FG003 | First Reference GXR (Fed), Then Test GXR (Fed) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt, Germany) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR (Merck Nantong, China) on Day 8 in treatment period 2 under fed conditions. There was a wash-out period of 7 days between each treatment period. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Day 1-Day 3) |
|
| |||||||||||||||||||||
| Treatment Period 2 (Day 8- Day 10) |
|
Safety population included all participants who received at least 1 dose of investigational medicinal product (IMP).
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| ID | Title | Description |
|---|---|---|
| BG000 | First Test GXR (Fasting), Then Reference GXR (Fasting) | Participants received a single oral dose of 500 milligrams (mg) of test GXR tablet (Merck Nantong, China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR (Merck Darmstadt, Germany) on Day 8 in treatment period 2 under fasting conditions. There was a wash-out period of 7 days between each 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 | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin | Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. | The Pharmacokinetic (PK) Analysis Set included all participants who completed the study with adequate study drug compliance, without any relevant protocol violations or events with respect to factors likely to affect comparability of PK results, and with sufficient evaluable data to determine primary outcome measures for both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*h/mL) | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
Time from informed consent up to end of study (Day 15)
The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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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 | Test GXR (Fasting) | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 19, 2018 | Nov 22, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 20, 2018 | Nov 22, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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|
|
| Reference GXR | Drug | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2). |
|
|
| Apparent Terminal Half-Life (t1/2) of Metformin |
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. |
| Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Metformin | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin | AUCextra% was defined as area under the curve from time tlast extrapolated to infinity as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Elimination Rate Constant (Lambda z) of Metformin | Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Total Body Clearance (CL/f) of Metformin | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin | Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing. | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease 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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs. | Time from informed consent up to end of study (Day 15) |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Vital sign assessment included blood pressure, pulse rate, body temperature and respiration (frequency per minute). Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator. | Time from informed consent up to end of study (Day 15) |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Values | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator. | Time from informed consent up to end of study (Day 15) |
| Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings | Physical examination included assessments of the general appearance, skin and mucosa, superficial lymph nodes, head and neck, chest, abdomen, musculoskeletal, and neurological systems. Number of participants with clinically significant abnormalities in physical examination findings were reported. clinically significance was decided by investigator. | Time from informed consent up to end of study (Day 15) |
| Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator. | Time from informed consent up to end of study (Day 15) |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | First Reference GXR (Fasting), Then Test GXR (Fasting) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt, Germany) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR (Merck Nantong, China) on Day 8 in treatment period 2 under fasting conditions. There was a wash-out period of 7 days between each treatment period. |
| BG002 | First Test GXR (Fed), Then Reference GXR (Fed) | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong, China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR (Merck Darmstadt, Germany) on Day 8 in treatment period 2 under fed conditions. There was a wash-out period of 7 days between each treatment period. |
| BG003 | First Reference GXR (Fed), Then Test GXR (Fed) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt, Germany) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR (Merck Nantong, China) on Day 8 in treatment period 2 under fed conditions. There was a wash-out period of 7 days between each treatment period. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. |
| OG001 | Reference GXR (Fasting) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. |
| OG002 | Test GXR (Fed) | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. |
| OG003 | Reference GXR (Fed) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Metformin | Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve. | The PK Analysis Set included all participants who completed the study with adequate study drug compliance, without any relevant protocol violations or events with respect to factors likely to affect comparability of PK results, and with sufficient evaluable data to determine primary outcome measures for both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
|
|
| Secondary | Time to Reach Maximum Plasma Concentration of Metformin | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | The PK Analysis Set included all participants who completed the study with adequate study drug compliance, without any relevant protocol violations or events with respect to factors likely to affect comparability of PK results, and with sufficient evaluable data to determine primary outcome measures for both treatments. | Posted | Median | Full Range | hours | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
|
|
| Secondary | Apparent Terminal Half-Life (t1/2) of Metformin | Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. | The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
|
| Secondary | Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Metformin | AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. | The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
|
|
| Secondary | Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin | AUCextra% was defined as area under the curve from time tlast extrapolated to infinity as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification. | As AUCextra was >20% of AUC0-inf, parameters derived from lambda z including AUCextra% were regarded as unreliable estimate of the extent of exposure and not calculated as it was pre-specified to not report these data in this condition. | Posted | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
| Secondary | Elimination Rate Constant (Lambda z) of Metformin | Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. | As AUCextra was >20% of AUC0-inf, parameters derived from lambda z were regarded as unreliable estimate of the extent of exposure and not calculated as it was pre-specified to not report these data in this condition. | Posted | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
| Secondary | Total Body Clearance (CL/f) of Metformin | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter per hour | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
|
| Secondary | Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin | Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing. | The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10 |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease 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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs. | The Safety Analysis Set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Time from informed consent up to end of study (Day 15) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in Vital Signs | Vital sign assessment included blood pressure, pulse rate, body temperature and respiration (frequency per minute). Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator. | The Safety Analysis Set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Time from informed consent up to end of study (Day 15) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in Laboratory Values | The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator. | The Safety Analysis Set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Time from informed consent up to end of study (Day 15) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings | Physical examination included assessments of the general appearance, skin and mucosa, superficial lymph nodes, head and neck, chest, abdomen, musculoskeletal, and neurological systems. Number of participants with clinically significant abnormalities in physical examination findings were reported. clinically significance was decided by investigator. | The Safety Analysis Set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Time from informed consent up to end of study (Day 15) |
|
|
|
| Secondary | Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator. | The Safety Analysis Set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Time from informed consent up to end of study (Day 15) |
|
|
|
| 0 |
| 37 |
| 0 |
| 37 |
| 10 |
| 37 |
| EG001 | Reference GXR (Fasting) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. | 0 | 37 | 0 | 37 | 11 | 37 |
| EG002 | Test GXR (Fed) | Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. | 0 | 16 | 0 | 16 | 3 | 16 |
| EG003 | Reference GXR (Fed) | Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. | 0 | 16 | 0 | 16 | 4 | 16 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 21.1 | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 21.1 | Non-systematic Assessment |
|
| Electrocardiogram ST segment abnormal | Investigations | MedDRA 21.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Non-systematic Assessment |
|
Not provided
Not provided
Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions. |
| Ratio of Geometric LS Mean Percentage |
| 96.89 |
| 2-Sided |
| 90 |
| 89.87 |
| 104.46 |
| Equivalence |
Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%. |
Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions. |
| Median point estimate difference |
| 0.00 |
| 2-Sided |
| 90 |
| -0.50 |
| 0.50 |
| Equivalence |
Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%. |
Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions. |
| Ratio of Geometric LS Mean Percentage |
| 98.08 |
| 2-Sided |
| 90 |
| 92.37 |
| 104.14 |
| Equivalence |
Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%. |
| Serious TEAEs |
|