Glucophage Extended Release (GXR) China Bioequivalence Study (Nantong - Darmstadt)

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03566810
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 4
• Actual Duration (Months): 1.6
• Patients Per Site Per Month: 34.2

Study Details

Study Description

Brief Summary

The study will assess the bioequivalence between single doses of GXR manufactured in Merck Nantong China (test drug) and GXR manufactured in Merck Darmstadt Germany (reference drug) under fed and fasted state in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Test GXR; Drug: Reference GXR	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Randomized, Open-label, 2-Way-Crossover Study Assessing the Bioequivalence Between Single Doses of 500 mg Glucophage Extended Release (GXR) Tablets (Merck/China Nantong-Manufactured) and 500 mg GXR Tablets (Merck/Germany Darmstadt-Manufactured) Under Fed and Fasted State in Two Groups of Healthy Volunteers
• Actual Study Start Date: Oct 11, 2018
• Actual Primary Completion Date: Nov 28, 2018
• Actual Study Completion Date: Nov 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Test GXR; Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride ; Drug: Reference GXR; Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride
Experimental: 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.	Drug: Test GXR; Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride ; Drug: Reference GXR; Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride
Experimental: 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.	Drug: Test GXR; Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride ; Drug: Reference GXR; Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride
Experimental: 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.	Drug: Test GXR; Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride ; Drug: Reference GXR; Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Other Names: Metformin hydrochloride

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin [Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10]

   Area under the plasma concentration 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.

2. Maximum Observed Plasma Concentration (Cmax) of Metformin [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]

   Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.

Secondary Outcome Measures

1. Time to Reach Maximum Plasma Concentration of Metformin [Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14 post-dose on Day 1 and Day 8; 24, 30, 36 hours post-dose on Day 2 and 9; 48 hours post-dose on Day 3 and 10]

   Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

2. Apparent Terminal Half-Life (t1/2) of Metformin [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]

   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.

3. Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Metformin [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]

   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.

4. Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin [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]

   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.

5. Elimination Rate Constant (Lambda z) of Metformin [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]

   Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

6. Total Body Clearance (CL/f) of Metformin [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]

   Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

7. Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin [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]

   Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.

8. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [Time from informed consent up to end of study (Day 15)]

   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.

9. Number of Participants With Clinically Significant Abnormalities in Vital Signs [Time from informed consent up to end of study (Day 15)]

   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.

10. Number of Participants With Clinically Significant Abnormalities in Laboratory Values [Time from informed consent up to end of study (Day 15)]

    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.

11. Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings [Time from informed consent up to end of study (Day 15)]

    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.

12. Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings [Time from informed consent up to end of study (Day 15)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy as determined by medical evaluation, including medical history and a physical examination

• Have a body weight within 50 to 90 kilogram (kg) and Body mass index (BMI) within the range 18 to 30 kg per meter square (kg/m^2) (inclusive)

• Chinese male and female (at least 1/4 of each gender per study group)

• A male participant must agree to use and to have their female partners use a highly effective contraception (that is, methods with a failure rate of less than 1 percent per year) for a period of at least 1 month before and after dosing

• A female is eligible if she is not pregnant (that is, after a confirmed menstrual period and a negative serum pregnancy test), not breastfeeding, and at least one of the following conditions applies

• Is not a woman of childbearing potential (WOCBP) OR

• Is a WOCBP who agrees to use a highly effective contraceptive method (that is, has a failure rate of less than 1 percent per year) for a period of at least 1 month before and after dosing

• Can give signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol

• Non-smoker (0 cigarettes, pipes, cigars, or others) since at least 3 months

• All values for biochemistry and hematology tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the Investigator

• Electrocardiogram recording (12 lead ECG) without signs of clinically relevant pathology as judged by the Investigator.

• Pulse, body temperature, and respiration in sitting position within the normal range or showing no clinically relevant deviation as judged by the Investigator. Blood pressure in sitting position within normal range: greater than or equals to (>=) 90 millimeter of mercury (mmHg) and less than or equal to (=<) 139 mmHg for systolic blood pressure; >= 60 mmHg and =< 90 mmHg for diastolic blood pressure

• Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, and methyl amphetamine) at screening and on admission

• Negative screen for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, and Treponema pallidum (TP) antibodies

Exclusion Criteria:

• Participation in a clinical trial within 90 days prior to first drug administration

• Blood donation (equal or more than 500 milliliter [mL]) or significant blood loss within 90 days prior to first drug administration

• Any surgical or medical condition, including findings in the medical history or in the pre-study assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the participant in the study or that could interfere with the study objectives, conduct or evaluation

• History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion

• History or presence of relevant liver diseases or hepatic dysfunction.

• Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study

• Receipt of any prescription or non-prescription medication within 2 weeks before the first Investigational medicinal product (IMP) administration, including multivitamins and herbal products (that is St John's Wort, or traditional Chinese medicines), except for the permitted medications

• Renal failure or renal dysfunction (creatinine clearance [Ccr] < 80 mL/minute) as assessed by using the estimated measure with the Cockcroft-Gault equation.

• Known lack of participant compliance or inability to communicate or cooperate with the Investigator (example, language problem, poor mental status)

• Non-acceptance of study high-fat breakfast (example, vegetarians, vegans and participants who follow special diets)

• Consumption of large quantities of methylxanthine-containing beverages (>5 cups of coffee/day or equivalent)

• Consumption of grapefruit, cranberry, or juices of these fruits, from 14 days prior to drug administration until collection of the last Pharmacokinetics sample in Period 2

• Any contraindication to Glucophage

• Abnormal and clinically significant chest X-ray finding at screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xuanwu Hospital Capital Medical University	Beijing		China

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck Pharmaceutical Manufacturing (Jiangsu) Co., Ltd., an affiliate of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Apr 19, 2018
• Statistical Analysis Plan - Dec 20, 2018

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT03566810
• Other Study ID Numbers: MS200084_0013
• First Posted: Jun 25, 2018
• Last Update Posted: Jan 9, 2020
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck KGaA, Darmstadt, Germany: Diabetes Mellitus; Glucophage Extended Release (GXR); Bioequivalence Study
• Additional relevant MeSH terms: Metformin

Study Results

Participant Flow

Arm/Group Title	First Test GXR (Fasting), Then Reference GXR (Fasting)	First Reference GXR (Fasting), Then Test GXR (Fasting)	First Test GXR (Fed), Then Reference GXR (Fed)	First Reference GXR (Fed), Then Test GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Period Title: Treatment Period 1 (Day 1-Day 3)
STARTED	19	19	8	8
Treated	19	18	8	8
COMPLETED	19	18	8	8
NOT COMPLETED	0	1	0	0
Period Title: Treatment Period 1 (Day 1-Day 3)
STARTED	19	18	8	8
COMPLETED	19	18	8	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	First Test GXR (Fasting), Then Reference GXR (Fasting)	First Reference GXR (Fasting), Then Test GXR (Fasting)	First Test GXR (Fed), Then Reference GXR (Fed)	First Reference GXR (Fed), Then Test GXR (Fed)	Total
Arm/Group Description	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.	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.	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.	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 of all reporting groups
Overall Participants	19	18	8	8	53
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.5 (8.00)	33.5 (8.79)	32.6 (7.13)	35.8 (11.15)	33.0 (8.55)
Sex: Female, Male (Count of Participants)
Female	6 31.6%	7 38.9%	3 37.5%	3 37.5%	19 35.8%
Male	13 68.4%	11 61.1%	5 62.5%	5 62.5%	34 64.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	19 100%	18 100%	8 100%	8 100%	53 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)]	3740 (31.5)	3780 (26.2)	5500 (17.1)	5540 (18.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fasting), Reference GXR (Fasting)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fasting conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric Least Square(LS)Mean%
	Estimated Value	98.69
	Confidence Interval	(2-Sided) 90%; 92.20 to 105.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fed), Reference GXR (Fed)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Mean Percentage
	Estimated Value	99.39
	Confidence Interval	(2-Sided) 90%; 93.15 to 106.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Metformin
Description	Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	572 (32.7)	578 (34.2)	519 (17.1)	536 (16.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fasting), Reference GXR (Fasting)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fasting conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Mean Percentage
	Estimated Value	98.92
	Confidence Interval	(2-Sided) 90%; 91.08 to 107.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fed), Reference GXR (Fed)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Mean Percentage
	Estimated Value	96.89
	Confidence Interval	(2-Sided) 90%; 89.87 to 104.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to Reach Maximum Plasma Concentration of Metformin
Description	Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Median (Full Range) [hours]	3.00	4.00	6.00	6.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fasting), Reference GXR (Fasting)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fasting conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median point estimate difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.50 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fed), Reference GXR (Fed)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median point estimate difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.50 to 0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Apparent Terminal Half-Life (t1/2) of Metformin
Description	Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	35	16	15
Geometric Mean (Geometric Coefficient of Variation) [hours]	5.80 (63.7)	5.56 (58.4)	5.34 (65.1)	5.37 (99.8)

5. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) of Metformin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	35	16	15
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	3890 (29.4)	3980 (25.0)	5630 (17.2)	5750 (19.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fasting), Reference GXR (Fasting)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fasting conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Mean Percentage
	Estimated Value	97.89
	Confidence Interval	(2-Sided) 90%; 91.38 to 104.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Test GXR (Fed), Reference GXR (Fed)
	Comments	Statistical Comparison of Test GXR Versus Reference GXR under Fed conditions.
	Type of Statistical Test	Equivalence
	Comments	Analysis was performed with Equivalence Acceptance Range for 90% Confidence Interval (CI) as 80.00% - 125.00%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Mean Percentage
	Estimated Value	98.08
	Confidence Interval	(2-Sided) 90%; 92.37 to 104.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	0	0	0	0

7. Secondary Outcome

Title	Elimination Rate Constant (Lambda z) of Metformin
Description	Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	0	0	0	0

8. Secondary Outcome

Title	Total Body Clearance (CL/f) of Metformin
Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	35	16	15
Geometric Mean (Geometric Coefficient of Variation) [liter per hour]	128 (29.4)	126 (25.0)	88.9 (17.2)	87.0 (19.2)

9. Secondary Outcome

Title	Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin
Description	Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Time Frame	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

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic analysis set. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	35	16	15
Geometric Mean (Geometric Coefficient of Variation) [liter]	1070 (75.6)	1010 (61.1)	684 (65.8)	674 (93.7)

10. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time Frame	Time from informed consent up to end of study (Day 15)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
TEAEs	10 52.6%	11 61.1%	3 37.5%	4 50%
Serious TEAEs	0 0%	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Vital Signs
Description	Vital sign assessment included blood pressure, pulse rate, body temperature and respiration (frequency per minute). Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator.
Time Frame	Time from informed consent up to end of study (Day 15)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Laboratory Values
Description	The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator.
Time Frame	Time from informed consent up to end of study (Day 15)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings
Description	Physical examination included assessments of the general appearance, skin and mucosa, superficial lymph nodes, head and neck, chest, abdomen, musculoskeletal, and neurological systems. Number of participants with clinically significant abnormalities in physical examination findings were reported. clinically significance was decided by investigator.
Time Frame	Time from informed consent up to end of study (Day 15)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Description	The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator.
Time Frame	Time from informed consent up to end of study (Day 15)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Test GXR (Fasting)	Reference GXR (Fasting)	Test GXR (Fed)	Reference GXR (Fed)
Arm/Group Description	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.	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.	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.	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.
Measure Participants	37	37	16	16
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Time from informed consent up to end of study (Day 15)
Adverse Event Reporting Description	The Safety Analysis Set included all participants who received at least 1 dose of study drug.
Arm/Group Title	Test GXR (Fasting)		Reference GXR (Fasting)		Test GXR (Fed)		Reference GXR (Fed)
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Test GXR (Fasting)		Reference GXR (Fasting)		Test GXR (Fed)		Reference GXR (Fed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Test GXR (Fasting)		Reference GXR (Fasting)		Test GXR (Fed)		Reference GXR (Fed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Test GXR (Fasting)		Reference GXR (Fasting)		Test GXR (Fed)		Reference GXR (Fed)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/37 (27%)		11/37 (29.7%)		3/16 (18.8%)		4/16 (25%)
Gastrointestinal disorders
Diarrhoea	8/37 (21.6%)		6/37 (16.2%)		1/16 (6.3%)		3/16 (18.8%)
Abdominal pain	2/37 (5.4%)		0/37 (0%)		1/16 (6.3%)		0/16 (0%)
Nausea	1/37 (2.7%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
Mouth ulceration	0/37 (0%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
Vomiting	0/37 (0%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
General disorders
Chest pain	0/37 (0%)		1/37 (2.7%)		0/16 (0%)		0/16 (0%)
Malaise	0/37 (0%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
Pyrexia	1/37 (2.7%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Infections and infestations
Upper respiratory tract infection	0/37 (0%)		3/37 (8.1%)		0/16 (0%)		0/16 (0%)
Furuncle	1/37 (2.7%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Oral herpes	0/37 (0%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
Investigations
White blood cell count decreased	1/37 (2.7%)		0/37 (0%)		1/16 (6.3%)		0/16 (0%)
Blood bilirubin increased	1/37 (2.7%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Electrocardiogram ST segment abnormal	0/37 (0%)		0/37 (0%)		1/16 (6.3%)		0/16 (0%)
Nervous system disorders
Dizziness	0/37 (0%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
Headache	1/37 (2.7%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Presyncope	0/37 (0%)		1/37 (2.7%)		0/16 (0%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/37 (0%)		1/37 (2.7%)		0/16 (0%)		0/16 (0%)
Hiccups	0/37 (0%)		0/37 (0%)		0/16 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Erythema	2/37 (5.4%)		0/37 (0%)		0/16 (0%)		0/16 (0%)
Rash	0/37 (0%)		1/37 (2.7%)		0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.