Bioequivalence and Drug - Drug Interaction Study of Metformin/Gliclazide in Healthy Participants
Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT03467945
Collaborator
(none)
40
1
4
2.4
16.9
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Randomized, Open Label, Single Dose, 4 Treatment, 4 Period, Crossover Design (4 x 4) Trial to Evaluate the Bioequivalence and Secondarily Drug - Drug Interaction of Fixed Combination of Metformin Tablets 1000 mg/Gliclazide 30 mg MR, Compared With the Co-administration of Individual Tablets and Individual Administration of Each Single Tablet (Metformin 1000 mg XR and Gliclazide 30 mg MR) in Healthy Volunteers
Actual Study Start Date
:
Feb 16, 2018
Actual Primary Completion Date
:
Apr 29, 2018
Actual Study Completion Date
:
Apr 29, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Sequence 1 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
Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.
Drug: Metformin
Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.
Drug: Gliclazide
Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.
|
| Experimental: Treatment Sequence 2 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
Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.
Drug: Metformin
Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.
Drug: Gliclazide
Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.
|
| Experimental: Treatment Sequence 3 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
Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.
Drug: Metformin
Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.
Drug: Gliclazide
Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.
|
| Experimental: Treatment Sequence 4 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
Participants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.
Drug: Metformin
Participants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.
Drug: Gliclazide
Participants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.
|
Outcome Measures
Primary Outcome Measures
- 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 [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]
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).
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) 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]
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).
Secondary Outcome Measures
- 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]
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
- 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]
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
- 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) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
- 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]
Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
- 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]
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
- Apparent Total Body Clearance (CL/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]
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
- Median Residence Time (MRT) for 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]
MRT is the average time that the molecules introduced into the body stays in the body.
- Median Residence Time (MRT) for 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]
MRT is the average time that the molecules introduced into the body stays in the body.
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Baseline up to Day 72]
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs included both Serious TEAEs and non-serious TEAEs.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Please Contact the Merck KGaA Communication Center | Darmstadt | Germany | 64293 |
Sponsors and Collaborators
- Merck KGaA, Darmstadt, Germany
Investigators
- Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT03467945
Other Study ID Numbers:
- EMR200763_003
First Posted:
Mar 16, 2018
Last Update Posted:
Jul 16, 2019
Last Verified:
Apr 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Merck KGaA, Darmstadt, Germany
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment Sequence 1 | Treatment Sequence 2 | Treatment Sequence 3 | Treatment Sequence 4 |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Treatment Period 1 | ||||
| STARTED | 10 | 10 | 10 | 10 |
| COMPLETED | 10 | 10 | 10 | 10 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: Treatment Period 1 | ||||
| STARTED | 10 | 10 | 10 | 10 |
| COMPLETED | 10 | 9 | 10 | 10 |
| NOT COMPLETED | 0 | 1 | 0 | 0 |
| Period Title: Treatment Period 1 | ||||
| STARTED | 10 | 9 | 10 | 10 |
| COMPLETED | 9 | 9 | 8 | 9 |
| NOT COMPLETED | 1 | 0 | 2 | 1 |
| Period Title: Treatment Period 1 | ||||
| STARTED | 9 | 9 | 8 | 9 |
| COMPLETED | 9 | 9 | 8 | 9 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment Sequence 1 | Treatment Sequence 2 | Treatment Sequence 3 | Treatment Sequence 4 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 10 | 10 | 10 | 10 | 40 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
22.8
(9.8)
|
23.9
(3.7)
|
31.5
(8.3)
|
25.7
(5.2)
|
27.3
(7.5)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
6
60%
|
3
30%
|
3
30%
|
5
50%
|
17
42.5%
|
| Male |
4
40%
|
7
70%
|
7
70%
|
5
50%
|
23
57.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
10
100%
|
10
100%
|
10
100%
|
10
100%
|
40
100%
|
| Not Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic (PK) analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [nanogram*hour per milliliter (ng*h/ml)] |
5033.8718
(1475.3418)
|
6142.2821
(1848.4857)
|
6090.7932
(1543.6463)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin and Gliclazide Separately |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 81.4421 | |
| Confidence Interval |
(2-Sided) 90% 75.2805 to 88.1079 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Metformin and Gliclazide Separately, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 102.2930 | |
| Confidence Interval |
(2-Sided) 90% 97.8819 to 106.9028 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 81.0112 | |
| Confidence Interval |
(2-Sided) 90% 74.8823 to 87.6417 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [ng.h/ml] |
20707.7394
(8267.0653)
|
20280.3103
(8219.1520)
|
21205.2514
(7638.0877)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin and Gliclazide Separately |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 102.2930 | |
| Confidence Interval |
(2-Sided) 90% 97.8819 to 106.9028 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Metformin and Gliclazide Separately, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 105.7255 | |
| Confidence Interval |
(2-Sided) 90% 101.1665 to 110.4900 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 96.7533 | |
| Confidence Interval |
(2-Sided) 90% 92.5812 to 101.1135 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximum Observed Plasma Concentration (Cmax) of Metformin |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [nanogram per milliliter (ng/ml)] |
806.3895
(279.5063)
|
1011.3941
(309.8136)
|
977.2693
(262.4312)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin and Gliclazide Separately |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 77.6923 | |
| Confidence Interval |
(2-Sided) 90% 70.3830 to 85.7606 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Metformin and Gliclazide Separately, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 108.0819 | |
| Confidence Interval |
(2-Sided) 90% 102.2370 to 114.2609 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 79.4367 | |
| Confidence Interval |
(2-Sided) 90% 71.9633 to 87.6861 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximum Observed Plasma Concentration (Cmax) of Gliclazide |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [ng/ml] |
972.168
(312.7305)
|
892.6201
(259.7459)
|
836.7239
(251.6451)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin and Gliclazide Separately |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 108.0819 | |
| Confidence Interval |
(2-Sided) 90% 102.2370 to 114.2609 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Metformin and Gliclazide Separately, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 93.6828 | |
| Confidence Interval |
(2-Sided) 90% 88.6166 to 99.0386 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 115.3700 | |
| Confidence Interval |
(2-Sided) 90% 109.1310 to 121.9658 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin |
|---|---|
| Description | 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). |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [ng*h/ml] |
5313.3897
(1549.2688)
|
6388.9849
(1857.6205)
|
6341.5658
(1560.7170)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin and Gliclazide Separately |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 82.6022 | |
| Confidence Interval |
(2-Sided) 90% 76.5513 to 89.1314 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Metformin and Gliclazide Separately, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 101.8499 | |
| Confidence Interval |
(2-Sided) 90% 97.8819 to 106.9028 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 81.0112 | |
| Confidence Interval |
(2-Sided) 90% 74.8823 to 87.6417 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Gliclazide |
|---|---|
| Description | 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). |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [ng*h/ml] |
21495.2343
(8358.3373)
|
21120.6761
(8270.5092)
|
22136.9988
(7687.4829)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin and Gliclazide Separately |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 101.8499 | |
| Confidence Interval |
(2-Sided) 90% 97.5947 to 106.2906 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Metformin and Gliclazide Separately, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 105.9150 | |
| Confidence Interval |
(2-Sided) 90% 101.4900 to 110.5330 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Metformin-Gliclazide Combination, Metformin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Bioequivalence boundaries of 80.000% to 125.00% were used. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Squares Mean Ratio |
| Estimated Value | 96.1619 | |
| Confidence Interval |
(2-Sided) 90% 92.1443 to 100.3546 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Apparent Volume of Distribution (Vz/f) of Metformin |
|---|---|
| Description | Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Milliliter] |
1893618.4672
(1346880.1198)
|
1414424.1926
(643556.2088)
|
1489164.0229
(818767.0681)
|
| Title | Apparent Volume of Distribution (Vz/f) of Gliclazide |
|---|---|
| Description | Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Milliliter] |
31636.8920
(7584.1651)
|
32601.0115
(7057.8050)
|
31413.9679
(6422.4920)
|
| Title | Elimination Half Life (t1/2) of Metformin |
|---|---|
| Description | Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Hours] |
6.7151
(5.1372)
|
5.9796
(2.8442)
|
6.3048
(3.7114)
|
| Title | Elimination Half Life (t1/2) of Gliclazide |
|---|---|
| Description | Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Hours] |
15.3086
(6.0231)
|
15.4587
(5.6007)
|
15.6222
(5.2904)
|
| Title | Apparent Total Body Clearance (CL/f) of Metformin |
|---|---|
| Description | CL/f was defined as apparent total clearance of the drug from plasma after oral administration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Milliliter per Hour (mL/ h)] |
207132.8293
(70959.4296)
|
170273.4024
(51108.0288)
|
167260.5841
(39170.7306)
|
| Title | Apparent Total Body Clearance (CL/f) of Gliclazide |
|---|---|
| Description | CL/f was defined as apparent total clearance of the drug from plasma after oral administration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [mL/h] |
1572.5246
(516.3724)
|
1606.8952
(569.4811)
|
1498.9932
(463.2158)
|
| Title | Median Residence Time (MRT) for Metformin |
|---|---|
| Description | MRT is the average time that the molecules introduced into the body stays in the body. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Hours] |
8.3952
(3.0758)
|
7.5836
(1.6807)
|
7.7636
(2.0658)
|
| Title | Median Residence Time (MRT) for Gliclazide |
|---|---|
| Description | MRT is the average time that the molecules introduced into the body stays in the body. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who completed the trial with adequate trial medication compliance, without any relevant protocol violations with respect to factors likely to affect the comparability of PK results. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Gliclazide |
|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 |
| Mean (Standard Deviation) [Hours] |
23.0593
(7.8010)
|
24.4927
(7.7484)
|
25.8590
(7.5834)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. TEAEs included both Serious TEAEs and non-serious TEAEs. |
| Time Frame | Baseline up to Day 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all participants who received at least 1 dose of the trial treatment. |
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin | Gliclazide |
|---|---|---|---|---|
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. |
| Measure Participants | 35 | 35 | 35 | 35 |
| TEAEs |
9
90%
|
6
60%
|
7
70%
|
8
80%
|
| SAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Baseline up to Day 72 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The safety population included all participants who received at least 1 dose of the trial treatment. | |||||||
| Arm/Group Title | Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin | Gliclazide | ||||
| Arm/Group Description | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg fixed combination tablet either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg and gliclazide 30 mg separately either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of metformin 1000 mg either in treatment period 1, 2, 3 or 4. | Participants received single oral dose of gliclazide 30mg either in treatment period 1, 2, 3 or 4. | ||||
All Cause Mortality |
||||||||
| Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin | Gliclazide | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | ||||
Serious Adverse Events |
||||||||
| Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin | Gliclazide | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Metformin-Gliclazide Combination | Metformin and Gliclazide Separately | Metformin | Gliclazide | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/35 (25.7%) | 6/35 (17.1%) | 7/35 (20%) | 8/35 (22.9%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 5/35 (14.3%) | 2/35 (5.7%) | 5/35 (14.3%) | 7/35 (20%) | ||||
| Gastrointestinal disorders | ||||||||
| Odynophagia | 0/35 (0%) | 1/35 (2.9%) | 0/35 (0%) | 1/35 (2.9%) | ||||
| Diarrhea | 0/35 (0%) | 0/35 (0%) | 1/35 (2.9%) | 1/35 (2.9%) | ||||
| Infectious gastroenteritis | 1/35 (2.9%) | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | ||||
| Vomiting | 0/35 (0%) | 1/35 (2.9%) | 0/35 (0%) | 0/35 (0%) | ||||
| Nausea | 0/35 (0%) | 0/35 (0%) | 1/35 (2.9%) | 0/35 (0%) | ||||
| Abdominal pain | 0/35 (0%) | 0/35 (0%) | 1/35 (2.9%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| Urinary infection | 1/35 (2.9%) | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | ||||
| Urethritis | 1/35 (2.9%) | 2/35 (5.7%) | 0/35 (0%) | 0/35 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Wound in the left submaxillary region | 1/35 (2.9%) | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | ||||
| Investigations | ||||||||
| Elevated triglycerides | 1/35 (2.9%) | 3/35 (8.6%) | 2/35 (5.7%) | 0/35 (0%) | ||||
| High cholesterol | 0/35 (0%) | 0/35 (0%) | 1/35 (2.9%) | 0/35 (0%) | ||||
| Elevated alanine aminostrasferase | 1/35 (2.9%) | 0/35 (0%) | 4/35 (11.4%) | 1/35 (2.9%) | ||||
| Elevated aspartate aminotrasferase | 1/35 (2.9%) | 0/35 (0%) | 5/35 (14.3%) | 1/35 (2.9%) | ||||
| Nervous system disorders | ||||||||
| Vasovagal reaction | 0/35 (0%) | 1/35 (2.9%) | 0/35 (0%) | 0/35 (0%) | ||||
| Headache | 1/35 (2.9%) | 0/35 (0%) | 0/35 (0%) | 1/35 (2.9%) | ||||
| Dizziness | 0/35 (0%) | 0/35 (0%) | 0/35 (0%) | 1/35 (2.9%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Communication Center |
|---|---|
| Organization | Merck KGaA, Darmstadt, Germany |
| Phone | +49-6151-72-5200 |
| service@emdgroup.com |
Responsible Party:
Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier:
NCT03467945
Other Study ID Numbers:
- EMR200763_003
First Posted:
Mar 16, 2018
Last Update Posted:
Jul 16, 2019
Last Verified:
Apr 1, 2019