Clinical trial NCT03467971: A Study to Assess the Food Effect on Bioavailability of Metformin/Gliclazide in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Metformin
Bioavailability
Food effect
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-03-16
Enrollment: 21
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 will assess the food effect on bioavailability of Metformin/Gliclazide fixed dose combination tablet in fed and fasted state.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin and Gliclazide
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin and Gliclazide
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Metformin and Gliclazide
timeFrame: 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 outcomes:
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Metformin and Gliclazide
timeFrame: 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
measure: Elimination Half Life (t1/2) of Metformin and Gliclazide
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/f) of Metformin and Gliclazide
timeFrame: 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
measure: Apparent Total Body Clearance (CL/f) of Metformin and Gliclazide From Plasma
timeFrame: 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
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 39
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: CECYPE
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: