A Study to Assess the Food Effect on Bioavailability of Metformin/Gliclazide in Healthy Participants

A Randomized, Open-label, Single Dose, 2x2 Crossover Trial to Evaluate the Food Effect on the Bioavailability of a Metformin/Gliclazide Fixed Combination Tablet (1000 mg /30 mg MR) Given in Fasting and Fed Conditions to Healthy Volunteers

This study will assess the food effect on bioavailability of Metformin/Gliclazide fixed dose combination tablet in fed and fasted state.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Metformin/Gliclazide Fixed Combination

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico
    • CECYPE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ethnicity: Mexicans
• Weight between 55 and 95 kilogram (kg)
• Body mass index between 18 and 27 kilogram per meter square (kg/m^2)
• Nonsmokers or participants who do not smoke more than 5 cigarettes or 1 pipe a day
• Good physical and mental health based on the clinical history and physical examination
• All results from blood chemistry, hematology, and urinalysis should be within normal ranges or without clinically significant deviations as per Principal Investigator's judgment
• Hematology complete blood count [CBC]: hematocrit and hemoglobin must be above the lower limit; upper limit may range up to 15 percent (%)
• Liver Function Test range as defined in the protocol
• Electrocardiogram (12 leads) without clinically significant pathological signs
• 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)
• Vital signs (blood pressure and pulse) in supine position within normal ranges or with clinically significant abnormalities as per the Principal Investigator's judgment
• All women of childbearing potential who are not pregnant or breastfeeding and who are using a highly effective contraceptive method for at least one month before and following dosing
• Negative result for alcohol breath test and urine test for drugs of abuse at screening and at each day -1 of the 2 treatment periods
• Negative serology tests for human immunodeficiency virus (HIV1 and HIV2 antibodies), hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV) and venereal disease research laboratory (VDRL) test screening
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants who have received any investigational drug within 21 days prior to the study start
• Participants who have donated or lost 450 milliliter (mL) or more of blood within 21 days prior to the study start
• Participants with history of cardiovascular, renal, liver, metabolic, gastrointestinal, neurological, endocrine, or hematopoietic (any type of anemia) diseases; mental disease, surgery or other organic abnormalities which might affect the study of the investigational drug pharmacokinetics
• History of gastrointestinal tract surgery
• Participants with history of hypersensitivity to the study drug and/or any formulation's ingredient; history of drug induced anaphylaxis
• Participants who take any other drug 30 days before the study drug dose and for which at least seven elimination half-lives had not elapsed
• Renal failure or renal impairment assessed by using the Cockcroft-Gault formula
• Participant's disagreement or lack of capacity to communicate and cooperate with the Investigator, lack of legal capacity or limited legal capacity which prevent him/her from continuing in the study
• Refusal of the high-fat diet which is necessary to assess the food effect. Considerable deviations to the diet's normal nutritional patterns
• Participants who have smoked tobacco, having drunk alcohol, or xanthines containing beverages or food above 600 mg of caffeine a day those who have had grilled food within 24 h prior to the drug dosing
• Intake of grapefruit, orange, cranberries or their juices within 14 days prior to the drug's dosing and throughout the study
• Legal inability or limited legal capacity
• Incarcerated participants
• Participants who have been exposed to agents known as liver enzyme systems' inducers or inhibitors, or who have taken potentially toxic drugs within 30 days prior to the study
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin-Gliclazide (fasted), Then Metformin-Gliclazide (fed); Participants received single dose of Metformin 1000 milligram (mg) and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 2. Each treatment period was separated by a 14-day wash-out period.	Drug: Metformin/Gliclazide Fixed Combination; Participants will receive single oral dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting or fed state.
Experimental: Metformin-Gliclazide (fed), Then Metformin-Gliclazide (fasted); Participants received single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fed state in treatment period 1 followed by single dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting state in treatment period 2. Each treatment period will be separated by a 14-day wash-out period.	Drug: Metformin/Gliclazide Fixed Combination; Participants will receive single oral dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting or fed state.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and 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, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide	AUC (0-t) is defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)	Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide	Cmax is defined as the maximum observed plasma concentration.	Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide	Tmax is defined as the time to reach maximum plasma concentration.	Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
Elimination Half Life (t1/2) of Metformin and Gliclazide	Elimination Half Life (t1/2) is 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, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide	Vz/f is defined as apparent volume of distribution during terminal phase after non-intravenous administration	Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma	CL/f is defined as apparent total clearance of the drug from plasma after oral administration.	Pre-dose, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0, 16.0, 24.0, 28.0, 32.0, 48.0, 72.0, 96.0, 120.0, 144.0 and 168.0 hour post-dose
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Adverse event(AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.	Baseline up to Day 39

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2018
• Primary Completion (Actual): April 22, 2018
• Study Completion (Actual): April 22, 2018

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 12, 2018
• First Posted (Actual): March 16, 2018

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: April 18, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Metformin; Food effect; Bioavailability
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Gliclazide
• Other Study ID Numbers: EMR200763_004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No