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Phase 1 N=40 Randomized Other

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

Healthy

Enrolled (actual)
40
Serious AEs
0.0%
Results posted
Jul 2019
Primary outcome: Primary: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin — 5033.8718; 6142.2821; 6090.7932 nanogram*hour per milliliter (ng*h/ml)

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Metformin/Gliclazide Fixed Combination (Drug); Metformin (Drug); Gliclazide (Drug)
Age
Adult · 18+ yrs
Sex
All
Sponsor
Merck KGaA, Darmstadt, Germany
Primary completion
Apr 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
5033.8718; 6142.2821; 6090.7932
PRIMARY
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide
20707.7394; 20280.3103; 21205.2514
PRIMARY
Maximum Observed Plasma Concentration (Cmax) of Metformin
806.3895; 1011.3941; 977.2693
PRIMARY
Maximum Observed Plasma Concentration (Cmax) of Gliclazide
972.168; 892.6201; 836.7239
PRIMARY
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin
5313.3897; 6388.9849; 6341.5658
PRIMARY
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide
21495.2343; 21120.6761; 22136.9988
SECONDARY
Apparent Volume of Distribution (Vz/f) of Metformin
1893618.4672; 1414424.1926; 1489164.0229
SECONDARY
Apparent Volume of Distribution (Vz/f) of Gliclazide
31636.8920; 32601.0115; 31413.9679
SECONDARY
Elimination Half Life (t1/2) of Metformin
6.7151; 5.9796; 6.3048
SECONDARY
Elimination Half Life (t1/2) of Gliclazide
15.3086; 15.4587; 15.6222
SECONDARY
Apparent Total Body Clearance (CL/f) of Metformin
207132.8293; 170273.4024; 167260.5841
SECONDARY
Apparent Total Body Clearance (CL/f) of Gliclazide
1572.5246; 1606.8952; 1498.9932
SECONDARY
Median Residence Time (MRT) for Metformin
8.3952; 7.5836; 7.7636
SECONDARY
Median Residence Time (MRT) for Gliclazide
23.0593; 24.4927; 25.8590
SECONDARY
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
9; 6; 7; 8; 0; 0

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.

Eligibility Criteria

Inclusion Criteria

  • 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
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria

  • 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
  • Other protocol defined exclusion criteria could apply
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03467945). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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