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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Metformin; Drug: Gliclazide; Drug: Metformin/Gliclazide Fixed Combination

Study type: Interventional

Funder types: Industry

Identifiers

NCT03467945

EMR200763_003

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

Treatment Sequence 1

Experimental group

Description:

Participants received single oral dose of metformin 1000 milligram (mg) and gliclazide 30 mg fixed combination tablet in treatment period 1 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg in treatment period 3 and then a single oral dose of gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Treatment:

Drug: Gliclazide

Drug: Metformin

Drug: Metformin/Gliclazide Fixed Combination

Treatment Sequence 2

Experimental group

Description:

Participants received concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 1 followed by single oral dose of gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 3 and then single oral dose of metformin 1000 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Treatment:

Drug: Gliclazide

Drug: Metformin

Drug: Metformin/Gliclazide Fixed Combination

Treatment Sequence 3

Experimental group

Description:

Participants received single oral dose of metformin 1000 mg in treatment period 1 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 2 followed by single oral dose of gliclazide 30 mg in treatment period 3 and then concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Treatment:

Drug: Gliclazide

Drug: Metformin

Drug: Metformin/Gliclazide Fixed Combination

Treatment Sequence 4

Experimental group

Description:

Participants received single oral dose of gliclazide 30 mg in treatment period 1 followed by single oral dose of metformin 1000 mg in treatment period 2 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 3 and then single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Treatment:

Drug: Gliclazide

Drug: Metformin

Drug: Metformin/Gliclazide Fixed Combination