Phase 1
N=40
Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT03467945 ↗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
| Outcome | Result | p-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
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.