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

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Metformin/Gliclazide Fixed Combination

Registration Number: NCT03467971

Lead Sponsor: Merck KGaA, Darmstadt, Germany

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Metformin-Gliclazide (fasted), Then Metformin-Gliclazide (fed)	Metformin/Gliclazide Fixed Combination	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.
Metformin-Gliclazide (fed), Then Metformin-Gliclazide (fasted)	Metformin/Gliclazide Fixed Combination	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.

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and Gliclazide	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	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).
Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide	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	Cmax is defined as the maximum observed plasma concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide	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	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)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Day 39	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.
Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide	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	Tmax is defined as the time to reach maximum plasma concentration.
Elimination Half Life (t1/2) of Metformin and Gliclazide	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) is defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide	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	Vz/f is defined as apparent volume of distribution during terminal phase after non-intravenous administration
Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma	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	CL/f is defined as apparent total clearance of the drug from plasma after oral administration.