Trial Outcomes & Findings for GXR RM (Glucophage® Extended Release Reduced Mass) 500 Milligram (mg) Korea Bioequivalence (BE) Study (NCT NCT04684420)
NCT ID: NCT04684420
Last Updated: 2023-12-29
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
81 participants
Primary outcome timeframe
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
Results posted on
2023-12-29
Participant Flow
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.
Participant milestones
| Measure |
First Reference GXR (Fasting), Then Test GXR RM Tablet (Fasting)
Participants received a single oral dose of 500 milligram (mg) of reference GXR (Glucophage® Extended Release) tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg test GXR RM (Reduced Mass) tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Treatment Period 1 (Day 1)
STARTED
|
24
|
24
|
17
|
16
|
|
Treatment Period 1 (Day 1)
COMPLETED
|
24
|
23
|
15
|
15
|
|
Treatment Period 1 (Day 1)
NOT COMPLETED
|
0
|
1
|
2
|
1
|
|
Period 2(Day 8 up to 3 Months)
STARTED
|
24
|
23
|
15
|
15
|
|
Period 2(Day 8 up to 3 Months)
COMPLETED
|
24
|
23
|
15
|
15
|
|
Period 2(Day 8 up to 3 Months)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
First Reference GXR (Fasting), Then Test GXR RM Tablet (Fasting)
Participants received a single oral dose of 500 milligram (mg) of reference GXR (Glucophage® Extended Release) tablet on Day 1 in treatment period 1 followed by single oral dose of 500 mg test GXR RM (Reduced Mass) tablet on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Treatment Period 1 (Day 1)
Withdrawal by Subject
|
0
|
0
|
2
|
1
|
|
Treatment Period 1 (Day 1)
Adverse Event
|
0
|
1
|
0
|
0
|
Baseline Characteristics
GXR RM (Glucophage® Extended Release Reduced Mass) 500 Milligram (mg) Korea Bioequivalence (BE) Study
Baseline characteristics by cohort
| Measure |
First Reference GXR (Fasting), Then Test GXR RM (Fasting)
n=24 Count of Participants
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.
|
First Test GXR RM (Fasting), Then Reference GXR (Fasting)
n=24 Count of Participants
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.
|
First Reference GXR (Fed), Then Test GXR RM (Fed)
n=17 Count of Participants
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.
|
First Test GXR RM (Fed), Then Reference GXR (Fed)
n=16 Count of Participants
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.
|
Total
n=81 Count of Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=93 Participants
|
24 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
81 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
22 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
13 Participants
n=483 Participants
|
59 Participants
n=36 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Asian
|
24 Participants
n=93 Participants
|
24 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
81 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: 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 dosePopulation: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=47 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
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
|
4076.521 hour*nanogram per milliter (hr*ng/ml)
Geometric Coefficient of Variation 30.4
|
6981.833 hour*nanogram per milliter (hr*ng/ml)
Geometric Coefficient of Variation 18.1
|
6564.938 hour*nanogram per milliter (hr*ng/ml)
Geometric Coefficient of Variation 26.4
|
PRIMARY outcome
Timeframe: 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 dosePopulation: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection.
Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=47 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Metformin
|
605.347 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 31.7
|
677.651 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 31.2
|
590.956 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 18.9
|
671.864 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 16.7
|
SECONDARY outcome
Timeframe: From Day 1 up to 3 weeksPopulation: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Serious TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
TEAEs
|
7 Participants
|
7 Participants
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From Day 1 up to 3 weeksPopulation: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
Concomitant medications included medications administered from the first administration of study interventions to the end of observation.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Number of Participants Taking Concomitant Medications
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Day1 (baseline) up to 3 weeksPopulation: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Blood Sugar Test (BST)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Hematology
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Biochemistry
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values
Urinalysis
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Day 1 (baseline) up to 3 weeksPopulation: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Day 1 (baseline) up to 3 weeksPopulation: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Day 1 (baseline) up to 3 weeksPopulation: The Safety Analysis Set included all participants who administered at least one dose of study interventions.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 dosePopulation: 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.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=47 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=29 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
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
|
4370.051 hr*ng/ml
Geometric Coefficient of Variation 28.6
|
7297.899 hr*ng/ml
Geometric Coefficient of Variation 16.4
|
6833.321 hr*ng/ml
Geometric Coefficient of Variation 23.6
|
SECONDARY outcome
Timeframe: 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 dosePopulation: 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.
The ratio of AUClast to AUCinf were reported.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=47 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=29 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
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
|
0.933 Ratio
Geometric Coefficient of Variation 3.2
|
0.953 Ratio
Geometric Coefficient of Variation 9.9
|
0.961 Ratio
Geometric Coefficient of Variation 3.5
|
SECONDARY outcome
Timeframe: 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 dosePopulation: 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.
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.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=47 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=29 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Apparent Terminal Half-Life (t1/2) of Metformin
|
3.520 hours
Geometric Coefficient of Variation 60.1
|
3.769 hours
Geometric Coefficient of Variation 47.1
|
4.122 hours
Geometric Coefficient of Variation 19.5
|
3.386 hours
Geometric Coefficient of Variation 21.1
|
SECONDARY outcome
Timeframe: 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 dosePopulation: Pharmacokinetic Analysis Set included those participants who completed investigational medicinal product (IMP) administration and completed all pharmacokinetic blood collection.
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Reference GXR (Fasting)
n=47 Participants
Participants received a single oral dose of 500 miligrams (mg) of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=47 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=30 Participants
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin
|
3.500 hours
Interval 2.0 to 5.0
|
3.500 hours
Interval 1.0 to 5.0
|
5.500 hours
Interval 4.0 to 10.0
|
5.010 hours
Interval 5.0 to 8.0
|
Adverse Events
Reference GXR (Fasting)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Test GXR RM (Fasting)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Reference GXR (Fed)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Test GXR RM (Fed)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Reference GXR (Fasting)
n=47 participants at risk
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fasting)
n=48 participants at risk
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fasting conditions. There was a washout period of 7 days between two treatment period.
|
Reference GXR (Fed)
n=32 participants at risk
Participants received a single oral dose of 500 mg of reference GXR tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
Test GXR RM (Fed)
n=31 participants at risk
Participants received a single oral dose of 500 mg of test GXR RM tablet either on Day 1 in treatment period 1 or on Day 8 in treatment period 2 under fed conditions. There was a washout period of 7 days between two treatment period.
|
|---|---|---|---|---|
|
Investigations
Human chorionic gonadotropin increased
|
4.3%
2/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
White blood cells urine positive
|
4.3%
2/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
4.2%
2/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
3.1%
1/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
3.2%
1/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
4.2%
2/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
6.2%
2/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
White blood cell count increased
|
0.00%
0/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
3.2%
1/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Blood creatine phosphokinase increased
|
2.1%
1/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
2.1%
1/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Alanine aminotransferase increased
|
2.1%
1/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Aspartate aminotransferase increased
|
2.1%
1/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Blood creatinine increased
|
2.1%
1/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
2.1%
1/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Blood lactic acid increased
|
2.1%
1/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Electrocardiogram PR prolongation
|
6.4%
3/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
4.2%
2/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
3.2%
1/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.1%
1/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
|
Investigations
Glomerular filtration rate decreased
|
0.00%
0/47 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
2.1%
1/48 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/32 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
0.00%
0/31 • From informed consent (Day-28 to Day-2) up to 3 weeks, a maximum of 49 days.
The Safety Analysis Set included all participants who administered at least one dose of study interventions.
|
Additional Information
Communication Center
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Phone: +49 6151 72 5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place