Healthy
Conditions
Keywords
Diabetes Mellitus, Glucophage Extended Release, Bioequivalence Study
Brief summary
The purpose of this study was to assess bioequivalence (BE) of newly developed Glucophage® XR (GXR) reduced mass (RM) tablet (metformin hydrochloride 500 milligrams (mg) test tablet) and marketed Glucophage ® XR tablet (metformin hydrochloride 500 mg reference tablet) following single oral dose administration under fasted and fed conditions by comparing pharmacokinetics, safety and tolerability between test and reference in healthy participants.
Interventions
DRUGGlucophage® XR RM Test
Participants received a single oral dose of 500 mg of test Glucophage® XR RM tablet under fasting or fed conditions.
DRUGGlucophage® XR Reference
Participants received a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* All values for hematology and biochemistry tests of blood and urinalysis (especially Estimated Glomerular Filtration Rate \[eGFR\] greater than \[\>\] 80 milliliters per minute per 1.73 square meter \[80 ml/min/1.73 m\^2\] and normal Creatinine) within the normal range or showing no clinically relevant deviation as judged by the Investigator * Are not having congenital or chronic diseases, nor pathological symptoms based on the screening * Have no history of gastrointestinal resection that may affect drug absorption * Have no history of psychiatric disorder within 5 years prior to screening * Vital signs (body temperature \[tympanic\], blood pressure \[BP\], and pulse rate in sitting 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) less than or equal to \[\<=\] 450 millisecond (ms) * Non-smoker (that is \[i.e.\] zero cigarettes, pipes, cigars or others) at least three months before study entry * Negative screen for Hepatitis B surface antigen (HBsAg) and Hepatitis B Virus antibody (anti-HBc), Hepatitis C Virus antibody (anti-HCV) and Human Immunodeficiency Virus antibodies (anti-HIV 1 and 2) and Rapid Plasma Reagin Antibody (RPR Ab) * Have a body weight within the range 55 to 95 kilograms (kg) and a Body Mass Index (BMI) within the range 18.5 to 29.9 kilograms per square meter (kg/m\^2) (inclusive) * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participants determined ineligible to participate in this study at the discretion of the Principal Investigator (or delegated investigators) * Hypersensitivity to venous puncture * Known hypersensitivity to ingredients of Study Interventions or Biguanides, or having other clinically relevant hypersensitivities * Type I diabetes mellitus, lactic acidosis, acute or chronic metabolic acidosis including diabetic ketoacidosis, with or without coma; diabetic pre-coma, pre-diabetes * Participants with renal impairment (eGFR \< 80 ml/min/1.73m\^2) - calculations according to Modification of Diet in Renal Disease (MDRD) formula). Participants presenting with acute conditions with the potential to alter renal function such as dehydration, severe infection, cardiovascular collapse (shock), acute myocardial infraction, and septicemia * Participants with acute and unstable heart failure * Participants with severe infection or severe traumatic general disorder * Participants who are scheduled to undergo surgical procedures * Participants with malnutrition, inanition, pituitary dysfunction or adrenal function failure * Participants with hepatic dysfunction, acute or chronic disease which may cause tissue hypoxia such as respiratory failure, acute myocardial infarction, shock and gastrointestinal (GI) disorder such as excessive alcohol intake, hydration, diarrhea, vomiting etc. * Participants undergoing intravascular administration of iodinated contrast materials in radio diagnostic examinations (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials etc.) * Participants who took drugs that significantly induce (e.g., barbiturate) or inhibit drug metabolism enzymes, and those drugs that may alter metformin pharmacokinetic (pK), most importantly organic cation transporter 1/2 \[OCT1/2\] inhibitors and inducers, within 30 days prior to screening * Use of a concomitant drug. However, any medications that are considered necessary for participant's welfare and will not interfere with the trial medication may be given at the discretion of the investigator * Use of any medication that may affect the outcome of the study within 10 days prior to screening and during study conduct * Participation in another bioequivalence or other clinical studies where the last administration of previous study medication was within 6 months, before the first drug administration in this study * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin | Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose | Area under the plasma concentration vs 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. |
| Maximum Observed Plasma Concentration (Cmax) of Metformin | Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose | Cmax was obtained directly from the concentration versus time curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | From Day1 (baseline) up to 3 weeks | The laboratory measurements included hematology, blood chemistry, urinalysis and Blood Sugar Test (BST). Number of participants with clinically significant changes from baseline in laboratory values were reported. Clinically Significance was decided by investigator. |
| Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | From Day 1 (baseline) up to 3 weeks | 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 changes from baseline in 12-lead ECG findings were reported. Clinically significance was decided by investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | From Day 1 (baseline) up to 3 weeks | Vital sign assessment included blood pressure, pulse rate, body temperature and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinically significance was decided by investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | From Day 1 (baseline) up to 3 weeks | Physical examination included assessments of the skin, lungs, cardiovascular system, abdomen (liver and spleen), and the symptoms reported by the participant. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinically significance was decided by investigator. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | From Day 1 up to 3 weeks | 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. |
| Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose | The ratio of AUClast to AUCinf were reported. |
| Apparent Terminal Half-Life (t1/2) of Metformin | Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose | 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. |
| Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose | AUC0-inf was calculated by combining AUC0-t and AUC extra. 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. |
| Number of Participants Taking Concomitant Medications | From Day 1 up to 3 weeks | Concomitant medications included medications administered from the first administration of study interventions to the end of observation. |
Countries
South Korea
Participant flow
Recruitment details
A total of 56 participants were screened for the study in Part 1 (Fasted state) out of which 48 were randomized. For Part 2 (Fed state), a total of 49 participants were screened out of which 33 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| First Reference GXR (Fasting), Then Test GXR RM (Fasting) Participants received a single oral dose of 500 mg of reference GXR tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg test GXR RM tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period. | 24 |
| First Reference GXR (Fasting), Then Test GXR RM (Fasting) Participants received a single oral dose of 500 mg of reference GXR tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg test GXR RM tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period. | 24 |
| First Test GXR RM (Fasting), Then Reference GXR (Fasting) Participants received a single oral dose of 500 milligrams (mg) of test GXR RM tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of reference GXR tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period. | 24 |
| First Test GXR RM (Fasting), Then Reference GXR (Fasting) Participants received a single oral dose of 500 milligrams (mg) of test GXR RM tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of reference GXR tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period. | 24 |
| First Reference GXR (Fed), Then Test GXR RM (Fed) Participants received a single oral dose of 500 milligrams (mg) of reference GXR tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of test GXR RM tablet on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period. | 17 |
| First Reference GXR (Fed), Then Test GXR RM (Fed) Participants received a single oral dose of 500 milligrams (mg) of reference GXR tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of test GXR RM tablet on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period. | 17 |
| First Test GXR RM (Fed), Then Reference GXR (Fed) Participants received a single oral dose of 500 milligrams (mg) of test GXR RM tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of reference GXR tablet on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period. | 16 |
| First Test GXR RM (Fed), Then Reference GXR (Fed) Participants received a single oral dose of 500 milligrams (mg) of test GXR RM tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg of reference GXR tablet on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period. | 16 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 (Day 1) | Adverse Event | 0 | 1 | 0 | 0 |
| Treatment Period 1 (Day 1) | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | First Test GXR RM (Fasting), Then Reference GXR (Fasting) | First Reference GXR (Fed), Then Test GXR RM (Fed) | First Reference GXR (Fasting), Then Test GXR RM (Fasting) | First Test GXR RM (Fed), Then Reference GXR (Fed) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 17 Participants | 24 Participants | 16 Participants | 81 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 17 Participants | 24 Participants | 16 Participants | 81 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 7 Participants | 3 Participants | 22 Participants |
| Sex: Female, Male Male | 17 Participants | 12 Participants | 17 Participants | 13 Participants | 59 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 / 47 | 0 / 48 | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 7 / 47 | 7 / 48 | 3 / 32 | 2 / 31 |
| serious Total, serious adverse events | 0 / 47 | 0 / 48 | 0 / 32 | 0 / 31 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin
Area under the plasma concentration vs 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.
Time frame: Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose
Population: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference GXR (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin | 3627.171 hour*nanogram per milliter (hr*ng/ml) | Geometric Coefficient of Variation 31.9 |
| Test GXR RM (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin | 4076.521 hour*nanogram per milliter (hr*ng/ml) | Geometric Coefficient of Variation 30.4 |
| Reference GXR (Fed) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin | 6981.833 hour*nanogram per milliter (hr*ng/ml) | Geometric Coefficient of Variation 18.1 |
| Test GXR RM (Fed) | Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin | 6564.938 hour*nanogram per milliter (hr*ng/ml) | Geometric Coefficient of Variation 26.4 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Metformin
Cmax was obtained directly from the concentration versus time curve.
Time frame: Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose
Population: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference GXR (Fasting) | Maximum Observed Plasma Concentration (Cmax) of Metformin | 605.347 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31.7 |
| Test GXR RM (Fasting) | Maximum Observed Plasma Concentration (Cmax) of Metformin | 677.651 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31.2 |
| Reference GXR (Fed) | Maximum Observed Plasma Concentration (Cmax) of Metformin | 590.956 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18.9 |
| Test GXR RM (Fed) | Maximum Observed Plasma Concentration (Cmax) of Metformin | 671.864 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 16.7 |
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.
Time frame: Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose
Population: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection. Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference GXR (Fasting) | Apparent Terminal Half-Life (t1/2) of Metformin | 3.520 hours | Geometric Coefficient of Variation 60.1 |
| Test GXR RM (Fasting) | Apparent Terminal Half-Life (t1/2) of Metformin | 3.769 hours | Geometric Coefficient of Variation 47.1 |
| Reference GXR (Fed) | Apparent Terminal Half-Life (t1/2) of Metformin | 4.122 hours | Geometric Coefficient of Variation 19.5 |
| Test GXR RM (Fed) | Apparent Terminal Half-Life (t1/2) of Metformin | 3.386 hours | Geometric Coefficient of Variation 21.1 |
Secondary
Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
AUC0-inf was calculated by combining AUC0-t and AUC extra. 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.
Time frame: Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose
Population: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection. Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference GXR (Fasting) | Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 3911.152 hr*ng/ml | Geometric Coefficient of Variation 30.8 |
| Test GXR RM (Fasting) | Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 4370.051 hr*ng/ml | Geometric Coefficient of Variation 28.6 |
| Reference GXR (Fed) | Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 7297.899 hr*ng/ml | Geometric Coefficient of Variation 16.4 |
| Test GXR RM (Fed) | Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 6833.321 hr*ng/ml | Geometric Coefficient of Variation 23.6 |
Secondary
Number of Participants Taking Concomitant Medications
Concomitant medications included medications administered from the first administration of study interventions to the end of observation.
Time frame: From Day 1 up to 3 weeks
Population: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reference GXR (Fasting) | Number of Participants Taking Concomitant Medications | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants Taking Concomitant Medications | 0 Participants |
| Reference GXR (Fed) | Number of Participants Taking Concomitant Medications | 0 Participants |
| Test GXR RM (Fed) | Number of Participants Taking Concomitant Medications | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline 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 changes from baseline in 12-lead ECG findings were reported. Clinically significance was decided by investigator.
Time frame: From Day 1 (baseline) up to 3 weeks
Population: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
The laboratory measurements included hematology, blood chemistry, urinalysis and Blood Sugar Test (BST). Number of participants with clinically significant changes from baseline in laboratory values were reported. Clinically Significance was decided by investigator.
Time frame: From Day1 (baseline) up to 3 weeks
Population: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Participants |
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Biochemistry | 0 Participants |
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Participants |
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Sugar Test (BST) | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Biochemistry | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Sugar Test (BST) | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Biochemistry | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Sugar Test (BST) | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Sugar Test (BST) | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Biochemistry | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
Physical examination included assessments of the skin, lungs, cardiovascular system, abdomen (liver and spleen), and the symptoms reported by the participant. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinically significance was decided by investigator.
Time frame: From Day 1 (baseline) up to 3 weeks
Population: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital sign assessment included blood pressure, pulse rate, body temperature and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinically significance was decided by investigator.
Time frame: From Day 1 (baseline) up to 3 weeks
Population: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reference GXR (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Reference GXR (Fed) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
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.
Time frame: From Day 1 up to 3 weeks
Population: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reference GXR (Fasting) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 7 Participants |
| Reference GXR (Fasting) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Test GXR RM (Fasting) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 7 Participants |
| Reference GXR (Fed) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 3 Participants |
| Reference GXR (Fed) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Test GXR RM (Fed) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 2 Participants |
| Test GXR RM (Fed) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
Secondary
Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin
The ratio of AUClast to AUCinf were reported.
Time frame: Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose
Population: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection. Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference GXR (Fasting) | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 0.927 Ratio | Geometric Coefficient of Variation 4.7 |
| Test GXR RM (Fasting) | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 0.933 Ratio | Geometric Coefficient of Variation 3.2 |
| Reference GXR (Fed) | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 0.953 Ratio | Geometric Coefficient of Variation 9.9 |
| Test GXR RM (Fed) | Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin | 0.961 Ratio | Geometric Coefficient of Variation 3.5 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time frame: Part 1 (fasted): Pre-dose and 0.5, 1, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24 and 32 hours post dose. Part 2 (fed): Pre-dose 1, 2, 3, 4, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 24 and 32 hours post dose
Population: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reference GXR (Fasting) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | 3.500 hours |
| Test GXR RM (Fasting) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | 3.500 hours |
| Reference GXR (Fed) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | 5.500 hours |
| Test GXR RM (Fed) | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin | 5.010 hours |