Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants

NCT03467945 | Completed Phase 1 Results

• 1 other identifier: EMR200763_003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Metformin; Gliclazide; Bioequivalence; Drug-drug Interaction; Pharmacokinetics

Outcome Measures

Primary Outcomes (6)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin

  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

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide

  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

• Maximum Observed Plasma Concentration (Cmax) of Metformin

  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

• Maximum Observed Plasma Concentration (Cmax) of Gliclazide

  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

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin

  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, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 28, 32, 48, 72, 96, 120, 144 and 168 hours post-dose

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of 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, 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 (9)

• Apparent Volume of Distribution (Vz/f) of Metformin

  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

• Apparent Volume of Distribution (Vz/f) of Gliclazide

  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

• Elimination Half Life (t1/2) of Metformin

  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

• Elimination Half Life (t1/2) of Gliclazide

  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

• Apparent Total Body Clearance (CL/f) of Metformin

  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

Study Arms (4)

Treatment Sequence 1

EXPERIMENTAL

Participants received single oral dose of metformin 1000 milligram (mg) and gliclazide 30 mg fixed combination tablet in treatment period 1 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg in treatment period 3 and then a single oral dose of gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Drug: Metformin/Gliclazide Fixed Combination; Drug: Metformin; Drug: Gliclazide

Treatment Sequence 2

EXPERIMENTAL

Participants received concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 1 followed by single oral dose of gliclazide 30 mg in treatment period 2 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 3 and then single oral dose of metformin 1000 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Drug: Metformin/Gliclazide Fixed Combination; Drug: Metformin; Drug: Gliclazide

Treatment Sequence 3

EXPERIMENTAL

Participants received single oral dose of metformin 1000 mg in treatment period 1 followed by single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 2 followed by single oral dose of gliclazide 30 mg in treatment period 3 and then concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Drug: Metformin/Gliclazide Fixed Combination; Drug: Metformin; Drug: Gliclazide

Treatment Sequence 4

EXPERIMENTAL

Participants received single oral dose of gliclazide 30 mg in treatment period 1 followed by single oral dose of metformin 1000 mg in treatment period 2 followed by concomitant oral dosing of metformin 1000 mg and gliclazide 30 mg in treatment period 3 and then single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet in treatment period 4. Each treatment period was separated by a 14-day wash-out period.

Drug: Metformin/Gliclazide Fixed Combination; Drug: Metformin; Drug: Gliclazide

Interventions

Metformin/Gliclazide Fixed Combination DRUG

Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Metformin DRUG

Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Gliclazide DRUG

Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Please Contact the Merck KGaA Communication Center

Darmstadt, 64293, Germany

Location

MeSH Terms

Interventions

Metformin; Gliclazide

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

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: February 16, 2018
• Primary Completion: April 29, 2018
• Study Completion: April 29, 2018
• Last Updated: July 16, 2019
• Results First Posted: July 16, 2019

Record last verified: 2019-04

Locations

DE (1)