Clinical trial NCT03467945: Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Metformin
Gliclazide
Bioequivalence
Drug-drug Interaction
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-03-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Metformin
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Gliclazide
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide
timeFrame: 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 outcomes:
measure: Apparent Volume of Distribution (Vz/f) of Metformin
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/f) of Gliclazide
timeFrame: 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
measure: Elimination Half Life (t1/2) of Metformin
timeFrame: 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
measure: Elimination Half Life (t1/2) of Gliclazide
timeFrame: 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
measure: Apparent Total Body Clearance (CL/f) of Metformin
timeFrame: 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
measure: Apparent Total Body Clearance (CL/f) of Gliclazide
timeFrame: 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
measure: Median Residence Time (MRT) for Metformin
timeFrame: 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
measure: Median Residence Time (MRT) for Gliclazide
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 72
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please Contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: