Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants

Healthy Clinical Trial

Official title:

Randomized, Open Label, Single Dose, 4 Treatment, 4 Period, Crossover Design (4 x 4) Trial to Evaluate the Bioequivalence and Secondarily Drug - Drug Interaction of Fixed Combination of Metformin Tablets 1000 mg/Gliclazide 30 mg MR, Compared With the Co-administration of Individual Tablets and Individual Administration of Each Single Tablet (Metformin 1000 mg XR and Gliclazide 30 mg MR) in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03467945
• Other study ID #: EMR200763_003
• Status: Completed
• Phase: Phase 1
• Start date: February 16, 2018
• Est. completion date: April 29, 2018

Study information

• Verified date: April 2019
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study investigated the bioequivalence and drug-drug interaction of Metformin/Gliclazide fixed combination tablet compared to co-administration of individual tablets of Metformin and Gliclazide.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 29, 2018
• Est. primary completion date: April 29, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participants has given written informed consent before any study-related activities were carried out

• Ethnic origin: Mexicans

• Weight between 55 and 95 kilogram (kg)

• Body mass index between 18.5 and 27 kilogram per meter square (kg/m^2)

• Not smoking more than 5 cigarettes or 1 cigar or 1 pipe per day (or non smokers)

• Good physical and mental health status

• Vital signs (blood pressure and pulse) in supine position within the normal range or showing no clinically relevant deviation as judged by the Investigator

• Electrocardiogram recording (12-lead) without signs of clinically relevant pathology in particular QTc (Bazett) <450 milliseconds (ms)

• 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

• All women of childbearing potential (WOCBP) were not nursing, were not pregnant, and were using highly effective methods of birth control for a period of at least one month before and after dosing

• All women of childbearing potential must have negative tests for pregnancy at screening, and at day -1 for each treatment period and at end of trial (EOT)

• Negative screen for alcohol and drugs of abuse at Screening and on each admission

• Negative screen for Hepatitis B surface (HBs) antigens, Hepatitis C Virus (HCV) antibodies, Hepatitis A Virus (HAV) antibodies and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

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

• Participants who have donated more than 500 milliliter (mL) of blood or who have lost significantly (more than 450 mL) blood within 90 days prior to first drug of administration

• Any surgical or medical condition, 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

• Allergy

• Receipt of any prescription or non-prescription medication within 2 weeks before the first study drug administration

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

• Known lack of participant compliance or inability to communicate or cooperate with the Investigator

• Considerable diet deviations from normal nutritional patterns

• Consumption of large quantities of methylxanthine-containing beverages (more than 600 milligram [mg] caffeine / day: one cup [240 mL] of coffee contains approx. 100 mg of caffeine, one cup of tea approximately 30 mg and one glass of cola approximately 20 mg caffeine)

• Consumption of grapefruit, orange, cranberry or juices of these fruits, 14 days prior to drug administration and during the study

• Legal incapacity or limited legal capacity

• Participants kept in detention

• Other protocol defined exclusion criteria could apply

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Metformin/Gliclazide Fixed Combination
Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.
• Metformin
Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.
• Gliclazide
Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.

Locations

Country	Name	City	State
Germany	Please Contact the Merck KGaA Communication Center	Darmstadt

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Primary	Maximum Observed Plasma Concentration (Cmax) of Metformin		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Primary	Maximum Observed Plasma Concentration (Cmax) of Gliclazide		Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Primary	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin	AUC (0-inf) is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Primary	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide	AUC (0-inf) is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Apparent Volume of Distribution (Vz/f) of Metformin	Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Apparent Volume of Distribution (Vz/f) of Gliclazide	Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Elimination Half Life (t1/2) of Metformin	Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Elimination Half Life (t1/2) of Gliclazide	Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Apparent Total Body Clearance (CL/f) of Metformin	CL/f was defined as apparent total clearance of the drug from plasma after oral administration.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Apparent Total Body Clearance (CL/f) of Gliclazide	CL/f was defined as apparent total clearance of the drug from plasma after oral administration.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Median Residence Time (MRT) for Metformin	MRT is the average time that the molecules introduced into the body stays in the body.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Median Residence Time (MRT) for Gliclazide	MRT is the average time that the molecules introduced into the body stays in the body.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 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. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs included both Serious TEAEs and non-serious TEAEs.	Baseline up to Day 72