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CompletedNCT03393208Updated Jul 15, 2019Results posted

Glucophage Immediate Release (GIR) China Bioequivalence Study

A Phase 1 interventional study of Test GIR and Reference GIR in Healthy, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in China. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-15.

Sponsored by Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
44
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The study will assess the bioequivalence between single doses of glucophage immediate release (GIR) test tablets and GIR reference tablets under fed and fasted state in healthy subjects.

02

Conditions studied

  • Healthy

Keywords

  • Diabetes Mellitus
  • Glucophage Immediate Release (GIR)
  • Bioequivalence Study
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Participants had given written informed consent before any trial-related activities
  • Chinese male and female participants (at least 1/4 of each gender per trial group)
  • Aged between 18 and 55 years, inclusive
  • Weighed: 50 to 80 kilogram (kg); Body mass index (BMI): 18 to 30 kg per meter square
  • Nonsmoker since at least 3 months
  • Good physical and mental health status, determined on the basis of the medical history and a physical examination
  • All values for biochemistry and hematology tests of blood and urine within the normal range or showied no clinically relevant deviation as judged by the Investigator
  • Electrocardiogram recording (12-lead ECG) without signs of clinically relevant pathology was judged by the Investigator
  • Vital signs (blood pressure, pulse, body temperature, and respiration) in sitting position within the normal range or showing no clinically relevant deviation was judged by the Investigator
  • All women of childbearing potential (WOCBP) who were not nursing, were not pregnant, and were using highly effective methods of birth control
  • Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, and methyl amphetamine) were screened at 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

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 pretrial 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 trial or that could interfere with the trial objectives, conducted or evaluated
  • 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 considered affectted the outcome of the trial
  • Receipt of any prescription or nonprescription medication within 2 weeks before the first IMP administration, including multivitamins and herbal products (example, St John's Wort, or traditional Chinese medicines), except paracetamol
  • Renal failure or renal dysfunction (creatinine clearance \< 80 mL/minute) as assessed by using the estimated measure with the Modification of Diet in Renal Disease (MDRD) equation
  • Known lack of participant compliance or inability to communicate or cooperate with the Investigator (example, language problem and poor mental status)
  • Nonacceptance of trial high-fat breakfast (example, vegetarians, vegans, and participants followed special diets)
  • Consumption of large quantities of methyl xanthine-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 pharmacokinetic sample in Period 2
  • Any contraindication to Glucophage
  • Abnormal and clinically significant chest X-ray finding at screening
04

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
44 participants (actual)

Study arms

  • Experimental
    First Test GIR (Fasting), Then Reference GIR (Fasting)

    Participants received a single oral dose of 500 milligram (mg) of test Glucophage Immediate Release (GIR) tablet Sino-American Shanghai Squibb (SASS)/China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (Merck Santé in Semoy (MSS)/France) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.

    Drug: Test GIR · Drug: Reference GIR

  • Experimental
    First Reference GIR (Fasting), Then Test GIR (Fasting)

    Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fasting condition. There was a wash-out period of 7 days between each treatment period.

    Drug: Test GIR · Drug: Reference GIR

  • Experimental
    First Test GIR (Fed), Then Reference GIR (Fed)

    Participants received a single oral dose of 500 mg of test GIR tablet (SASS/ China) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GIR (MSS/France) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.

    Drug: Test GIR · Drug: Reference GIR

  • Experimental
    First Reference GIR (Fed), Then Test GIR (Fed)

    Participants received a single oral dose of 500 mg of reference GIR tablet (MSS/ France) on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GIR (SASS/China) on Day 8 in treatment period 2 under fed condition. There was a wash-out period of 7 days between each treatment period.

    Drug: Test GIR · Drug: Reference GIR

Interventions

  • DrugTest GIR

    Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).

    Also known as: Metformin

  • DrugReference GIR

    Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).

    Also known as: Metformin

05

What researchers measure

Primary outcomes

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)

    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  2. Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)

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

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

Secondary outcomes

  1. Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)

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

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  2. Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)

    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 λz.

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  3. Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)

    AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, 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 λz 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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  4. Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin (GIR Tablet Active Ingredient)

    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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  5. Elimination Rate Constant (λz) of Metformin (GIR Tablet Active Ingredient)

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

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  6. Total Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient)

    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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  7. Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient)

    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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  8. Apparent Volume of Distribution at Steady-State After Extravascular Administration (Vss/f) of Metformin

    Vss/F was derived from concentration versus time data for all participants.

    Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

  9. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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

    Time frame: Baseline up to Day 15

  10. Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-lead Electrocardiogram (ECG) Findings

    The laboratory measurements included hematology, blood chemistry and urinalysis. Vital sign assessment included blood pressure, pulse rate and body temperature. ECG parameters included heart rate, PR, QRS,QT, RR, QTcB and QTcF Here, we are reporting number of participants with clinically significant abnormalities in Vital signs, laboratory parameters, physical findings and ECG findings.

    Time frame: Baseline up to Day 15

06

Results

Posted Jul 15, 2019

Participant flow

Treatment Period 1 (Day 1-Day 3)
Participant flow — Treatment Period 1 (Day 1-Day 3)
MilestoneFirst Test GIR (Fasting), Then Reference GIR (Fasting)First Reference GIR (Fasting), Then Test GIR (Fasting)First Test GIR (Fed), Then Reference GIR (Fed)First Reference GIR (Fed), Then Test GIR (Fed)
Started131399
Completed131399
Not completed0000
Treatment Period 2 (Day 8- Day 10)
Participant flow — Treatment Period 2 (Day 8- Day 10)
MilestoneFirst Test GIR (Fasting), Then Reference GIR (Fasting)First Reference GIR (Fasting), Then Test GIR (Fasting)First Test GIR (Fed), Then Reference GIR (Fed)First Reference GIR (Fed), Then Test GIR (Fed)
Started131399
Completed131399
Not completed0000

Outcome measures

PrimaryArea Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Geometric mean · nanogram hour per milliliter (ng*h/mL)
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)
nanogram hour per milliliter (ng*h/mL)Treatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient)6260 ± 22.46280 ± 16.34950 ± 25.65020 ± 23.3
Statistical analysis
  • Treatment A: Test GIR (Fasting) vs Treatment B Reference GIR (Fasting) · Ratio of geometric leastsquare(ls) mean%: 99.76 · 90% CI 92.84 to 107.20
  • Treatment A: Test GIR (Fed) vs Treatment B: Reference GIR (Fed) · Ratio of geometric ls mean percentage: 98.67 · 90% CI 91.25 to 106.69
PrimaryMaximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)
ng/mLTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient)1110 ± 30.11110 ± 22.7711 ± 22.4700 ± 18.6
Statistical analysis
  • Treatment A: Test GIR (Fasting) vs Treatment B Reference GIR (Fasting) · Ratio of geometric ls mean percentage: 99.62 · 90% CI 92.69 to 106.77
  • Treatment A: Test GIR (Fed) vs Treatment B: Reference GIR (Fed) · Ratio of geometric ls mean percentage: 101.50 · 90% CI 93.72 to 109.92
SecondaryTime to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Median · hours
Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)
hoursTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient)2.00 (1.00 to 4.00)2.00 (1.00 to 4.00)2.75 (1.50 to 5.00)2.75 (1.00 to 4.00)
Statistical analysis
  • Treatment A: Test GIR (Fasting) vs Treatment B Reference GIR (Fasting) · Median difference: 0.00 · 90% CI -0.25 to 0.25
  • Treatment A: Test GIR (Fed) vs Treatment B: Reference GIR (Fed) · Median difference: 0.25 · 90% CI -0.25 to 0.50
SecondaryApparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)

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 λz.

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Geometric mean · hours
Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)
hoursTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient)4.38 ± 40.54.90 ± 47.44.23 ± 45.64.16 ± 67.3
SecondaryArea Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ λz, 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 λz 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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Geometric mean · ng*h/mL
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)
ng*h/mLTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient)6520 ± 20.26410 ± 16.05070 ± 25.05160 ± 21.2
Statistical analysis
  • Treatment A: Test GIR (Fasting) vs Treatment B Reference GIR (Fasting) · Ratio of geometric ls mean percentage: 101.26 · 90% CI 94.33 to 108.69
  • Treatment A: Test GIR (Fed) vs Treatment B: Reference GIR (Fed) · Ratio of geometric ls mean percentage: 98.17 · 90% CI 91.61 to 105.21
SecondaryArea Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin (GIR Tablet Active Ingredient)

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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

No measurements were reported for this outcome.

SecondaryElimination Rate Constant (λz) of Metformin (GIR Tablet Active Ingredient)

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

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

No measurements were reported for this outcome.

SecondaryTotal Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient)

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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Geometric mean · liter per hour
Total Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient)
liter per hourTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Total Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient)76.7 ± 20.278.0 ± 16.098.6 ± 25.096.8 ± 21.2
SecondaryApparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient)

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, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Reported as:
Geometric mean · liter
Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient)
literTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient)485 ± 46.6551 ± 52.5602 ± 34.3581 ± 73.1
SecondaryApparent Volume of Distribution at Steady-State After Extravascular Administration (Vss/f) of Metformin

Vss/F was derived from concentration versus time data for all participants.

Time frame:
Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3

No measurements were reported for this outcome.

SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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

Time frame:
Baseline up to Day 15
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
ParticipantsTreatment A: Test GIR (Fasting)Treatment B Reference GIR (FastingTreatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Any TEAE2223
Serious TEAE0000
SecondaryNumber of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-lead Electrocardiogram (ECG) Findings

The laboratory measurements included hematology, blood chemistry and urinalysis. Vital sign assessment included blood pressure, pulse rate and body temperature. ECG parameters included heart rate, PR, QRS,QT, RR, QTcB and QTcF Here, we are reporting number of participants with clinically significant abnormalities in Vital signs, laboratory parameters, physical findings and ECG findings.

Time frame:
Baseline up to Day 15
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-lead Electrocardiogram (ECG) Findings
ParticipantsTreatment A: Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
Vital Signs0000
Laboratory Parameters0000
Physical Examination0000
12-Lead Electrocardiogram (ECG)0000

Adverse events

Collected over Baseline up to Day 15. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment A Test GIR (Fasting)0/26 (0%)0/26 (0%)2/26 (7.7%)
Treatment B Reference GIR (Fasting)0/26 (0%)0/26 (0%)2/26 (7.7%)
Treatment A: Test GIR (Fed)0/18 (0%)0/18 (0%)2/18 (11.1%)
Treatment B: Reference GIR (Fed)0/18 (0%)0/18 (0%)3/18 (16.7%)
Most frequent other events
Most frequent other events
EventTreatment A Test GIR (Fasting)Treatment B Reference GIR (Fasting)Treatment A: Test GIR (Fed)Treatment B: Reference GIR (Fed)
DiarrheaGastrointestinal disorders1/262/261/182/18
Abdominal distensionGastrointestinal disorders0/260/262/181/18
Abdominal painGastrointestinal disorders0/260/261/181/18
Frequent bowel movementsGastrointestinal disorders0/260/260/181/18
AnemiaBlood and lymphatic system disorders1/260/260/180/18

Baseline characteristics

Age, Continuous
Age, Continuous(years)First Test GIR (Fasting), Then Reference GIR (Fasting)First Reference GIR (Fasting), Then Test GIR (Fasting)First Test GIR (Fed), Then Reference GIR (Fed)First Reference GIR (Fed), Then Test GIR (Fed)Total
Mean32.8 ± 7.9731.5 ± 7.3929.8 ± 9.0132.2 ± 7.0331.7 ± 7.65
Sex: Female, Male
Sex: Female, Male(Participants)First Test GIR (Fasting), Then Reference GIR (Fasting)First Reference GIR (Fasting), Then Test GIR (Fasting)First Test GIR (Fed), Then Reference GIR (Fed)First Reference GIR (Fed), Then Test GIR (Fed)Total
Female343414
Male1096530
Race (NIH/OMB)
Race (NIH/OMB)(Participants)First Test GIR (Fasting), Then Reference GIR (Fasting)First Reference GIR (Fasting), Then Test GIR (Fasting)First Test GIR (Fed), Then Reference GIR (Fed)First Reference GIR (Fed), Then Test GIR (Fed)Total
American Indian or Alaska Native00000
Asian13139944
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White00000
More than one race00000
Unknown or Not Reported00000
07

Study locations

1 site
  • Xuanwu Hospital
    Beijing, 100053, China
08

References and documents

Publications

  • Hu C, Gao D, Li D, Zhou D, Zhang L. Chinese- and French-Manufactured Immediate-Release Glucophage(R) Bioequivalence: A Randomized, Open-Label, Crossover Study. Drugs R D. 2022 Dec;22(4):301-309. doi: 10.1007/s40268-022-00405-3. Epub 2022 Oct 20. PubMed 36264446 ↗

Study documents

  • Study protocol · Nov 20, 2017
  • Statistical analysis plan · Jan 29, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03393208
Lead sponsor
Merck KGaA, Darmstadt, Germany
Responsible party
Sponsor
First posted
Jan 8, 2018
Start date
Jan 10, 2018
Primary completion
Jan 29, 2018
Completion
Jan 29, 2018
Results posted
Jul 15, 2019
Last update
Jul 15, 2019

Study contacts

Medical Responsible
study director · Merck KGaA, Darmstadt, Germany

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

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Merck KGaA, Darmstadt, Germany

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