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

NCT03467971 | Completed Phase 1 Results

• 1 other identifier: EMR200763_004
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Metformin; Bioavailability; Food effect; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

• 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

• 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

• 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

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to Day 39

Study Arms (2)

Metformin-Gliclazide (fasted), Then Metformin-Gliclazide (fed)

EXPERIMENTAL

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

Metformin-Gliclazide (fed), Then Metformin-Gliclazide (fasted)

EXPERIMENTAL

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

Interventions

Metformin/Gliclazide Fixed Combination DRUG

Participants will receive single oral dose of Metformin 1000 mg and Gliclazide 30 mg fixed combination tablet in fasting or fed state.

Metformin-Gliclazide (fasted), Then Metformin-Gliclazide (fed); Metformin-Gliclazide (fed), Then Metformin-Gliclazide (fasted)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

CECYPE

Mexico City, Mexico

Location

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 16, 2018
• Study Start: March 6, 2018
• Primary Completion: April 22, 2018
• Study Completion: April 22, 2018
• Last Updated: July 8, 2019
• Results First Posted: July 8, 2019

Record last verified: 2019-04

Locations

ME (1)