Trial Outcomes & Findings for Glucophage Extended Release (GXR) China Bioequivalence Study (Nantong - Darmstadt) (NCT NCT03566810)
NCT ID: NCT03566810
Last Updated: 2020-01-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
54 participants
Primary outcome timeframe
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
Results posted on
2020-01-09
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Treatment Period 1 (Day 1-Day 3)
STARTED
|
19
|
19
|
8
|
8
|
|
Treatment Period 1 (Day 1-Day 3)
Treated
|
19
|
18
|
8
|
8
|
|
Treatment Period 1 (Day 1-Day 3)
COMPLETED
|
19
|
18
|
8
|
8
|
|
Treatment Period 1 (Day 1-Day 3)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Treatment Period 2 (Day 8- Day 10)
STARTED
|
19
|
18
|
8
|
8
|
|
Treatment Period 2 (Day 8- Day 10)
COMPLETED
|
19
|
18
|
8
|
8
|
|
Treatment Period 2 (Day 8- Day 10)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Treatment Period 1 (Day 1-Day 3)
Enrolled, but never treated
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Glucophage Extended Release (GXR) China Bioequivalence Study (Nantong - Darmstadt)
Baseline characteristics by cohort
| Measure |
First Test GXR (Fasting), Then Reference GXR (Fasting)
n=19 Participants
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)
n=18 Participants
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)
n=8 Participants
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)
n=8 Participants
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.
|
Total
n=53 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
31.5 years
STANDARD_DEVIATION 8.00 • n=93 Participants
|
33.5 years
STANDARD_DEVIATION 8.79 • n=4 Participants
|
32.6 years
STANDARD_DEVIATION 7.13 • n=27 Participants
|
35.8 years
STANDARD_DEVIATION 11.15 • n=483 Participants
|
33.0 years
STANDARD_DEVIATION 8.55 • n=36 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
19 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
34 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
|
19 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
53 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: 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 10Population: 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.
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.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin
|
3740 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 31.5
|
3780 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 26.2
|
5500 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 17.1
|
5540 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 18.7
|
PRIMARY outcome
Timeframe: 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 10Population: 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.
Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Metformin
|
572 ng/mL
Geometric Coefficient of Variation 32.7
|
578 ng/mL
Geometric Coefficient of Variation 34.2
|
519 ng/mL
Geometric Coefficient of Variation 17.1
|
536 ng/mL
Geometric Coefficient of Variation 16.4
|
SECONDARY outcome
Timeframe: 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 10Population: 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.
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration of Metformin
|
3.00 hours
Interval 1.0 to 5.0
|
4.00 hours
Interval 1.0 to 5.0
|
6.00 hours
Interval 3.0 to 10.0
|
6.00 hours
Interval 5.0 to 8.0
|
SECONDARY outcome
Timeframe: 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 10Population: The Pharmacokinetic analysis set. 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 |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=35 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=15 Participants
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.
|
|---|---|---|---|---|
|
Apparent Terminal Half-Life (t1/2) of Metformin
|
5.80 hours
Geometric Coefficient of Variation 63.7
|
5.56 hours
Geometric Coefficient of Variation 58.4
|
5.34 hours
Geometric Coefficient of Variation 65.1
|
5.37 hours
Geometric Coefficient of Variation 99.8
|
SECONDARY outcome
Timeframe: 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 10Population: The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
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.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=35 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=15 Participants
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.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Metformin
|
3890 ng*h/mL
Geometric Coefficient of Variation 29.4
|
3980 ng*h/mL
Geometric Coefficient of Variation 25.0
|
5630 ng*h/mL
Geometric Coefficient of Variation 17.2
|
5750 ng*h/mL
Geometric Coefficient of Variation 19.2
|
SECONDARY outcome
Timeframe: 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 10Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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 10Population: 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.
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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 10Population: The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=35 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=15 Participants
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.
|
|---|---|---|---|---|
|
Total Body Clearance (CL/f) of Metformin
|
128 liter per hour
Geometric Coefficient of Variation 29.4
|
126 liter per hour
Geometric Coefficient of Variation 25.0
|
88.9 liter per hour
Geometric Coefficient of Variation 17.2
|
87.0 liter per hour
Geometric Coefficient of Variation 19.2
|
SECONDARY outcome
Timeframe: 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 10Population: The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=35 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=15 Participants
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.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin
|
1070 liter
Geometric Coefficient of Variation 75.6
|
1010 liter
Geometric Coefficient of Variation 61.1
|
684 liter
Geometric Coefficient of Variation 65.8
|
674 liter
Geometric Coefficient of Variation 93.7
|
SECONDARY outcome
Timeframe: Time from informed consent up to end of study (Day 15)Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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 |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
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
|
10 Participants
|
11 Participants
|
3 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Time from informed consent up to end of study (Day 15)Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Time from informed consent up to end of study (Day 15)Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Laboratory Values
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Time from informed consent up to end of study (Day 15)Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Time from informed consent up to end of study (Day 15)Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Test GXR (Fasting)
n=37 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.
|
Reference GXR (Fasting)
n=37 Participants
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.
|
Test GXR (Fed)
n=16 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 fed conditions.
|
Reference GXR (Fed)
n=16 Participants
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.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Test GXR (Fasting)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Reference GXR (Fasting)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Test GXR (Fed)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Reference GXR (Fed)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Test GXR (Fasting)
n=37 participants at risk
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.
|
Reference GXR (Fasting)
n=37 participants at risk
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.
|
Test GXR (Fed)
n=16 participants at risk
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.
|
Reference GXR (Fed)
n=16 participants at risk
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.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
21.6%
8/37 • 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.
|
16.2%
6/37 • 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.
|
6.2%
1/16 • 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.
|
18.8%
3/16 • 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.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.4%
2/37 • 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.
|
0.00%
0/37 • 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.
|
6.2%
1/16 • 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.
|
0.00%
0/16 • 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.
|
|
Gastrointestinal disorders
Nausea
|
2.7%
1/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/37 • 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.
|
8.1%
3/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Infections and infestations
Furuncle
|
2.7%
1/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
|
Investigations
White blood cell count decreased
|
2.7%
1/37 • 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.
|
0.00%
0/37 • 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.
|
6.2%
1/16 • 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.
|
0.00%
0/16 • 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.
|
|
Investigations
Blood bilirubin increased
|
2.7%
1/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Investigations
Electrocardiogram ST segment abnormal
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
6.2%
1/16 • 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.
|
0.00%
0/16 • 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.
|
|
General disorders
Chest pain
|
0.00%
0/37 • 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.
|
2.7%
1/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
General disorders
Malaise
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
|
General disorders
Pyrexia
|
2.7%
1/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
|
Nervous system disorders
Headache
|
2.7%
1/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/37 • 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.
|
2.7%
1/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.4%
2/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/37 • 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.
|
2.7%
1/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/37 • 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.
|
2.7%
1/37 • 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.
|
0.00%
0/16 • 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.
|
0.00%
0/16 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/37 • 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.
|
0.00%
0/37 • 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.
|
0.00%
0/16 • 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.
|
6.2%
1/16 • 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.
|
Additional Information
Communication Center
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