HealthyPhase 1NCT03467945

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

A Phase 1 study testing Metformin/Gliclazide Fixed Combination, Metformin and Gliclazide in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Metformin/Gliclazide Fixed Combination, Metformin and Gliclazide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteGermany
Study dates: 16 Feb 2018to 29 Apr 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

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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

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Please Contact the Merck KGaA Communication Center
Darmstadt, 64293

Other trials in Germany

About this study

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

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
Being tested: Metformin/Gliclazide Fixed Combination, Metformin, Gliclazide
Keywords: Metformin, Gliclazide, Bioequivalence, Drug-drug Interaction, Pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03467945
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Metformin/Gliclazide Fixed Combination; Drug: Metformin; Drug: Gliclazide

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
Measured: 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
Measured: 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
Measured: 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
Measured: 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).
Measured: 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).
Measured: 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
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
Measured: 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
Vz/f was defined as apparent volume of distribution during terminal phase after non-intravenous administration.
Measured: 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
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.
Measured: 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
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.
Measured: 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
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
Measured: 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 Gliclazide
CL/f was defined as apparent total clearance of the drug from plasma after oral administration.
Measured: 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
Median Residence Time (MRT) for Metformin
MRT is the average time that the molecules introduced into the body stays in the body.
Measured: 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
Median Residence Time (MRT) for Gliclazide
MRT is the average time that the molecules introduced into the body stays in the body.
Measured: 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
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Measured: Baseline up to Day 72

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Feb 201829 Apr 2018

First posted16 Mar 2018
Study start16 Feb 2018
Primary completion29 Apr 2018
Study completion29 Apr 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03467945
Sponsor's protocol ID: EMR200763_003
Status last verified: Apr 2019
First submitted: 12 Mar 2018
Last updated: 16 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 16 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03467945
Acronym / sponsor ID: EMR200763_003
Conditions: Healthy
Keywords: Metformin, Gliclazide, Bioequivalence, Drug-drug Interaction, Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 16 Feb 2018 (actual)
Primary completion: 29 Apr 2018 (actual)
Study completion: 29 Apr 2018 (actual)
First posted: 16 Mar 2018 (actual)
Results: Posted 16 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Treatment Sequence 1	Experimental	Drug: Metformin/Gliclazide Fixed Combination, Drug: Metformin, Drug: GliclazideParticipants 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.
Treatment Sequence 2	Experimental	Drug: Metformin/Gliclazide Fixed Combination, Drug: Metformin, Drug: GliclazideParticipants 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.
Treatment Sequence 3	Experimental	Drug: Metformin/Gliclazide Fixed Combination, Drug: Metformin, Drug: GliclazideParticipants 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.
Treatment Sequence 4	Experimental	Drug: Metformin/Gliclazide Fixed Combination, Drug: Metformin, Drug: GliclazideParticipants 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (14 listed)

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)

Key exclusion criteria (14 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Metformin/Gliclazide Fixed CombinationParticipants received single oral dose of Metformin and Gliclazide fixed combination tablet in treatment period 1, 2, 3 or 4.	Drug	Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4
MetforminParticipants received single oral dose of Metformin tablet in treatment period 1, 2, 3 or 4.	Drug	Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4
GliclazideParticipants received single oral dose of Gliclazide tablet in treatment period 1, 2, 3 or 4.	Drug	Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4

Primary outcome

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin
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
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Gliclazide
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
Maximum Observed Plasma Concentration (Cmax) of Metformin
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
Maximum Observed Plasma Concentration (Cmax) of Gliclazide
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
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Metformin
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
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
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
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).

9 secondary outcomes

Apparent Volume of Distribution (Vz/f) of Metformin
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
Apparent Volume of Distribution (Vz/f) of Gliclazide
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
Elimination Half Life (t1/2) of Metformin
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
Elimination Half Life (t1/2) of Gliclazide
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
Apparent Total Body Clearance (CL/f) of Metformin
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
Apparent Total Body Clearance (CL/f) of Gliclazide
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
Median Residence Time (MRT) for Metformin
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
Median Residence Time (MRT) for Gliclazide
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
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Day 72

Results and safety

Results posted to the registry on 16 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Sequence 1	10	10
Treatment Sequence 2	10	10
Treatment Sequence 3	10	10
Treatment Sequence 4	10	10

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

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. Mean (Standard Deviation). Unit: nanogram*hour per milliliter (ng*h/ml)

Measure	Metformin-Gliclazide Combination n = 35	Metformin and Gliclazide Separately n = 35	Metformin n = 35
Value	5033.8718 (1475.3418)	6142.2821 (1848.4857)	6090.7932 (1543.6463)

Metformin-Gliclazide Combination vs Metformin and Gliclazide Separately: Geometric Least Squares Mean Ratio: 81.4421 (90% CI 75.2805 to 88.1079)
Metformin and Gliclazide Separately vs Metformin: Geometric Least Squares Mean Ratio: 102.2930 (90% CI 97.8819 to 106.9028)
Metformin-Gliclazide Combination vs Metformin: Geometric Least Squares Mean Ratio: 81.0112 (90% CI 74.8823 to 87.6417)

Population analysed: 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.

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

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. Mean (Standard Deviation). Unit: ng.h/ml

Measure	Metformin-Gliclazide Combination n = 35	Metformin and Gliclazide Separately n = 35	Gliclazide n = 35
Value	20707.7394 (8267.0653)	20280.3103 (8219.1520)	21205.2514 (7638.0877)

Metformin-Gliclazide Combination vs Metformin and Gliclazide Separately: Geometric Least Squares Mean Ratio: 102.2930 (90% CI 97.8819 to 106.9028)
Metformin and Gliclazide Separately vs Gliclazide: Geometric Least Squares Mean Ratio: 105.7255 (90% CI 101.1665 to 110.4900)
Metformin-Gliclazide Combination vs Gliclazide: Geometric Least Squares Mean Ratio: 96.7533 (90% CI 92.5812 to 101.1135)

Population analysed: 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.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Metformin

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. Mean (Standard Deviation). Unit: nanogram per milliliter (ng/ml)

Measure	Metformin-Gliclazide Combination n = 35	Metformin and Gliclazide Separately n = 35	Metformin n = 35
Value	806.3895 (279.5063)	1011.3941 (309.8136)	977.2693 (262.4312)

Metformin-Gliclazide Combination vs Metformin and Gliclazide Separately: Geometric Least Squares Mean Ratio: 77.6923 (90% CI 70.3830 to 85.7606)
Metformin and Gliclazide Separately vs Metformin: Geometric Least Squares Mean Ratio: 108.0819 (90% CI 102.2370 to 114.2609)
Metformin-Gliclazide Combination vs Metformin: Geometric Least Squares Mean Ratio: 79.4367 (90% CI 71.9633 to 87.6861)

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Gliclazide

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. Mean (Standard Deviation). Unit: ng/ml

Measure	Metformin-Gliclazide Combination n = 35	Metformin and Gliclazide Separately n = 35	Gliclazide n = 35
Value	972.168 (312.7305)	892.6201 (259.7459)	836.7239 (251.6451)

Metformin-Gliclazide Combination vs Metformin and Gliclazide Separately: Geometric Least Squares Mean Ratio: 108.0819 (90% CI 102.2370 to 114.2609)
Metformin and Gliclazide Separately vs Gliclazide: Geometric Least Squares Mean Ratio: 93.6828 (90% CI 88.6166 to 99.0386)
Metformin-Gliclazide Combination vs Gliclazide: Geometric Least Squares Mean Ratio: 115.3700 (90% CI 109.1310 to 121.9658)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to Day 72. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Metformin-Gliclazide Combination	0 of 35 (0%)	9 of 35 (25.7%)	0 of 35
Metformin and Gliclazide Separately	0 of 35 (0%)	6 of 35 (17.1%)	0 of 35
Metformin	0 of 35 (0%)	7 of 35 (20%)	0 of 35
Gliclazide	0 of 35 (0%)	8 of 35 (22.9%)	0 of 35

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Metformin/Gliclazide Fixed Combination, Metformin and Gliclazide in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Metformin (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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03467945.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2019.