HealthyPhase 1InPedILD®NCT05083949

A Study in Healthy Humans to Assess the Relative Bioavailability of One Fixed-dose Combination Tablet Empagliflozin/Metformin Versus Jardiance® Tablet and Glifage® Tablet Administered Together

A Phase 1 study testing FDC 12.5mg empagliflozin/850mg metformin, Empagliflozin and Glifage® in people with Healthy, run by Boehringer Ingelheim at 1 site in Brazil.

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 trial is to establish bioequivalence of the fixed dose combination (FDC) tablets (containing 12.5 mg empagliflozin/850 mg metformin) (Test, T) compared with the single tablets (10 mg empagliflozin and Glifage® 850 mg tablets) (Reference, R). Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: FDC 12.5mg empagliflozin/850mg metformin, Empagliflozin and Glifage®
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteBrazil
Study dates: 23 Jul 2021to 9 Sep 2021
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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
Age of at least 18 (inclusive) to 50 years (inclusive)
Body mass index (BMI) of 18.5 to 29.9 weight divided by height squared (kg/m2) (inclusive)
Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
Male subjects, or female subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:
Use of adequate contraception, e.g. any of the following methods plus condom:

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implants, injectables, combined oral or vaginal contraceptives, intrauterine device
Sexually abstinent
A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
Surgically sterilised (including hysterectomy)

Who cannot join

Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
History of relevant orthostatic hypotension, fainting spells, or blackouts
Chronic or relevant acute infections

Show all 11Show fewer

Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause time from the start of the Q wave to the end of the T wave (QT) / corrected QT (QTc) interval prolongation)
Smoker (more than 5 cigarettes or 1 cigar or 1 pipe per day)
Detection or indeterminate / inconclusive result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Coronavirus ribonucleic acid (RNA) in the quantitative real-time polymerase chain reaction (RT-qPCR) exam performed on the day before the admission of each period;
The research participant presents symptoms of coronavirus disease 2019 (COVID-19) infection (even if the result is "undetected" in the RT-PCR exam for COVID-19)
Further exclusion criteria apply

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Instituto de Ciências Farmacêuticas de Estudos e Pesquisas - ICF
Goiânia, 74935-530

Other trials in Brazil

About this study

Official title: Relative Bioavailability of Empagliflozin/Metformin Fixed-dose Combination - Empagliflozin 12.5 mg + Metformin 850mg (Boehringer Ingelheim) Coated Tablet Versus Jardiance® 10mg (Reference 1: Boehringer Ingelheim) Coated Tablet and Glifage® 850mg (Reference 2: Merck S / A. ) Coated Tablet, Administered Together in Healthy Male and Female Subjects Under Fed Conditions: an Open-label, Randomised, Single-dose, Two-way Crossover Study

Conditions: Healthy
Being tested: FDC 12.5mg empagliflozin/850mg metformin, Empagliflozin, Glifage®

What participants receive

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

FDC 12.5mg empagliflozin/850mg metforminDrug
empagliflozin/metformin
EmpagliflozinDrug
empagliflozin 10mg (R1)
Glifage®Drug
Also called metformin
Glifage® 850mg (R2)

Study groups in NCT05083949
Study group	Role	What they receive
(A): empagliflozin 10mg (R1)+Glifage® 850mg (R2),then (B): FDC 12.5mg empagliflozin/850mg metformin	Experimental	On Day 1 of Period 1 subjects received treatment A: Single dose tablet of 10 milligram(mg) empagliflozin film-coated and a 850mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200 milliliter(mL) of water. On Day 1 of Period 2 subjects received treatment B: Fixed dose combination (FDC) tablet of 12.5mg empagliflozin/850 mg metformin HCl, orally with 200mL of water. A high-fat, high-calorie meal was served 30 minutes(min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days. Receives: Drug: FDC 12.5mg empagliflozin/850mg metformin; Drug: Empagliflozin; Drug: Glifage®
(B): FDC 12.5mg empagliflozin/850mg metformin,then (A): empagliflozin 10mg(R1) + Glifage® 850mg(R2)	Experimental	On Day 1 of Period 1 subjects received treatment B: Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. On Day 1 of Period 2 subjects received treatment A: Single dose tablet of 10mg empagliflozin and 850 mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200mL of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days. Receives: Drug: FDC 12.5mg empagliflozin/850mg metformin; Drug: Empagliflozin; Drug: Glifage®

What is being measured

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

Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) normalized to the actual administered dose is presented. The AUC0-tz was divided by the actual dose strength to get the normalized area under the concentration-time curve. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Unit of measure:(hour*nanogram/milliliter)/milligram.
Measured: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Dose-normalized Maximum Measured Concentration of Empagliflozin (Cmax)
Dose-normalized Maximum measured concentration of empagliflozin in plasma is presented. The maximum measured concentration was divided by the actual dose strength to get the dose-normalised Cmax. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. The unit of measure reported is: (nanogram/milliliter)/milligram.
Measured: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Maximum Measured Concentration of Metformin (Cmax)
Maximum measured concentration of metformin in plasma is presented. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.

Secondary outcomes (10)

Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ )
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity from the last quantifiable data point (AUC0-inf) normalized to the actual administered dose is presented. The AUC0-oo was divided by the actual dose strength to get the normalized area under the concentration-time curve. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Unit of measure: (hour*nanogram/milliliter)/milligram.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞ ) is presented. The statistical model used for the analysis was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Time From Last Dosing to the Maximum Measured Concentration of Empagliflozin in Plasma (Tmax)
Time from last dosing to the maximum measured concentration of empagliflozin in plasma (tmax) is presented.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Time From Last Dosing to the Maximum Measured Concentration of Metformin in Plasma (Tmax)
Time from last dosing to the maximum measured concentration of metformin in plasma (tmax) is presented.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Percentage (%) of the AUC of Empagliflozin That Has Been Derived After Extrapolation
The percentage (%) of the AUC of empagliflozin that has been derived after extrapolation is reported.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Percentage (%) of the AUC of Metformin That Has Been Derived After Extrapolation
The percentage (%) of the AUC of metformin that has been derived after extrapolation is reported.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Terminal Half-life of Empagliflozin in Plasma (t1/2)
The terminal half-life of empagliflozin in plasma (t1/2) is presented.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Terminal Half-life of Metformin in Plasma (t1/2)
The terminal half-life of metformin in plasma (t1/2) is presented.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Elimination Rate Constant (Kel) for Empagliflozin
The elimination rate constant (Kel) for empagliflozin is reported.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Elimination Rate Constant (Kel) for Metformin
The elimination rate constant (Kel) for metformin is reported.
Measured: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.

Timeline

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

23 Jul 20219 Sep 2021

First posted19 Oct 2021
Study start23 Jul 2021
Primary completion6 Aug 2021
Study completion9 Sep 2021

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.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
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: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05083949
Sponsor's protocol ID: 1276-0041
Acronym: InPedILD®
Status last verified: Sep 2022
First submitted: 6 Oct 2021
Last updated: 27 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to:https://www.mystudywindow.com/msw/datasharing

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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All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Relative Bioavailability of Empagliflozin/Metformin Fixed-dose Combination - Empagliflozin 12.5 mg + Metformin 850mg (Boehringer Ingelheim) Coated Tablet Versus Jardiance® 10mg (Reference 1: Boehringer Ingelheim) Coated Tablet and Glifage® 850mg (Reference 2: Merck S / A. ) Coated Tablet, Administered Together in Healthy Male and Female Subjects Under Fed Conditions: an Open-label, Randomised, Single-dose, Two-way Crossover Study
ClinicalTrials.gov ID: NCT05083949
Acronym / sponsor ID: InPedILD® / 1276-0041
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 23 Jul 2021 (actual)
Primary completion: 6 Aug 2021 (actual)
Study completion: 9 Sep 2021 (actual)
First posted: 19 Oct 2021 (actual)
Results: Posted 27 Jul 2023

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
(A): empagliflozin 10mg (R1)+Glifage® 850mg (R2),then (B): FDC 12.5mg empagliflozin/850mg metformin	Experimental	Drug: FDC 12.5mg empagliflozin/850mg metformin, Drug: Empagliflozin, Drug: Glifage®On Day 1 of Period 1 subjects received treatment A: Single dose tablet of 10 milligram(mg) empagliflozin film-coated and a 850mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200 milliliter(mL) of water. On Day 1 of Period 2 subjects received treatment B: Fixed dose combination (FDC) tablet of 12.5mg empagliflozin/850 mg metformin HCl, orally with 200mL of water. A high-fat, high-calorie meal was served 30 minutes(min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.
(B): FDC 12.5mg empagliflozin/850mg metformin,then (A): empagliflozin 10mg(R1) + Glifage® 850mg(R2)	Experimental	Drug: FDC 12.5mg empagliflozin/850mg metformin, Drug: Empagliflozin, Drug: Glifage®On Day 1 of Period 1 subjects received treatment B: Fixed dose combination (FDC) tablet containing 12.5 milligram (mg) empagliflozin/850 mg metformin HCl, orally with 200 milliliter (mL) of water. On Day 1 of Period 2 subjects received treatment A: Single dose tablet of 10mg empagliflozin and 850 mg of metformin hydrochloride (HCl) (Glifage®) tablet, orally with 200mL of water. A high-fat, high-calorie meal was served 30 minutes (min) before drug administration. The treatments were separated by a wash-out phase of at least 7 days.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
Age of at least 18 (inclusive) to 50 years (inclusive)
Body mass index (BMI) of 18.5 to 29.9 weight divided by height squared (kg/m2) (inclusive)
Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
Male subjects, or female subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:

Key exclusion criteria (11 listed)

Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
History of relevant orthostatic hypotension, fainting spells, or blackouts

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
FDC 12.5mg empagliflozin/850mg metforminempagliflozin/metformin	Drug	(A): empagliflozin 10mg (R1)+Glifage® 850mg (R2),then (B): FDC 12.5mg empagliflozin/850mg metformin, (B): FDC 12.5mg empagliflozin/850mg metformin,then (A): empagliflozin 10mg(R1) + Glifage® 850mg(R2)
Empagliflozinempagliflozin 10mg (R1)	Drug	(A): empagliflozin 10mg (R1)+Glifage® 850mg (R2),then (B): FDC 12.5mg empagliflozin/850mg metformin, (B): FDC 12.5mg empagliflozin/850mg metformin,then (A): empagliflozin 10mg(R1) + Glifage® 850mg(R2)
Glifage®Also: metforminGlifage® 850mg (R2)	Drug	(A): empagliflozin 10mg (R1)+Glifage® 850mg (R2),then (B): FDC 12.5mg empagliflozin/850mg metformin, (B): FDC 12.5mg empagliflozin/850mg metformin,then (A): empagliflozin 10mg(R1) + Glifage® 850mg(R2)

Primary outcome

Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time frame: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) normalized to the actual administered dose is presented. The AUC0-tz was divided by the actual dose strength to get the normalized area under the concentration-time curve. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Unit of measure:(hour*nanogram/milliliter)/milligram.
Dose-normalized Maximum Measured Concentration of Empagliflozin (Cmax)
Time frame: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Dose-normalized Maximum measured concentration of empagliflozin in plasma is presented. The maximum measured concentration was divided by the actual dose strength to get the dose-normalised Cmax. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. The unit of measure reported is: (nanogram/milliliter)/milligram.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.
Maximum Measured Concentration of Metformin (Cmax)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Maximum measured concentration of metformin in plasma is presented. The statistical model used for the analysis of the primary endpoints was an analysis of variance (ANOVA) on the logarithmic scale. That is, the PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period and treatment. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.

10 secondary outcomes

Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞ )
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Time From Last Dosing to the Maximum Measured Concentration of Empagliflozin in Plasma (Tmax)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Time From Last Dosing to the Maximum Measured Concentration of Metformin in Plasma (Tmax)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Percentage (%) of the AUC of Empagliflozin That Has Been Derived After Extrapolation
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Percentage (%) of the AUC of Metformin That Has Been Derived After Extrapolation
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Terminal Half-life of Empagliflozin in Plasma (t1/2)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Terminal Half-life of Metformin in Plasma (t1/2)
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Elimination Rate Constant (Kel) for Empagliflozin
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.
Elimination Rate Constant (Kel) for Metformin
Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.

Results and safety

Results posted to the registry on 27 Jul 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
(A): Empagliflozin 10mg (R1)+Glifage® 850mg (R2),Then (B): FDC 12.5mg Empagliflozin/850mg Metformin	16	13
(B): FDC 12.5mg Empagliflozin/850mg Metformin,Then (A): Empagliflozin 10mg(R1) + Glifage® 850mg(R2)	16	14

Primary outcome: Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

Time frame: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.. Geometric least squares mean (Standard Error). Unit: (h*ng/mL)/mg

Measure	(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) n = 24	(B): FDC 12.5mg Empagliflozin/850mg Metformin n = 24
Value	117.15 (NA)	116.65 (NA)

(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) vs (B): FDC 12.5mg Empagliflozin/850mg Metformin: Ratio of GLSM (%): 99.57 (90% CI 97.03 to 102.19), p = 0.7792, ANOVA

Population analysed: Pharmacokinetic (PK) parameter analysis set (PKS): This set included all subjects who provided all PK endpoints for all treatment periods that were defined as primary (Cmax and AUCo-tz) and was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability. Only subjects with non-missing values were included.

Primary outcome: Dose-normalized Maximum Measured Concentration of Empagliflozin (Cmax)

Measure	(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) n = 24	(B): FDC 12.5mg Empagliflozin/850mg Metformin n = 24
Value	13.42 (NA)	13.60 (NA)

(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) vs (B): FDC 12.5mg Empagliflozin/850mg Metformin: Ratio of GLSM (%): 101.36 (90% CI 96.39 to 106.59), p = 0.6493, ANOVA

Primary outcome: Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.. Geometric least squares mean (Standard Error). Unit: hour*nanogram/milliliter (h*ng/mL)

Measure	(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) n = 24	(B): FDC 12.5mg Empagliflozin/850mg Metformin n = 24
Value	10299.45 (NA)	10467.41 (NA)

(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) vs (B): FDC 12.5mg Empagliflozin/850mg Metformin: Ratio of GLSM (%): 101.63 (90% CI 97.85 to 105.55), p = 0.4710, ANOVA

Primary outcome: Maximum Measured Concentration of Metformin (Cmax)

Time frame: Within 5 minutes(min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.. Geometric least squares mean (Standard Error). Unit: nanogram/milliliter (ng/mL )

Measure	(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) n = 24	(B): FDC 12.5mg Empagliflozin/850mg Metformin n = 24
Value	1333.58 (NA)	1308.39 (NA)

(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2) vs (B): FDC 12.5mg Empagliflozin/850mg Metformin: Ratio of GLSM (%): 98.11 (90% CI 94.24 to 102.15), p = 0.4251, ANOVA

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days after the last treatment administration.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
(A): Empagliflozin 10mg (R1) + Metformin (Glifage®) 850mg (R2)	0 of 30 (0%)	5 of 30 (16.7%)	0 of 30
(B): FDC 12.5mg Empagliflozin/850mg Metformin	0 of 29 (0%)	2 of 29 (6.9%)	0 of 29

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to:https://www.mystudywindow.com/msw/datasharing

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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.

The record lists no contact. Use the official record to reach the sponsor.

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 FDC 12.5mg empagliflozin/850mg metformin, Empagliflozin and Glifage® in people with Healthy, run by Boehringer Ingelheim at 1 site in Brazil.

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 10 inclusion and 11 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 27 Jul 2023. 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 Brazil. 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 27 Jul 2023). 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?

Dose-normalized Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (time frame: Within 5 minutes (min) before and 15min, 30min, 45min, 1h, 1h15min, 1h30min, 1h45min, 2h, 2h20min, 2h40min, 3h, 3h30min, 4h, 4h30min, 5h, 5h30min, 6h, 7h, 8h, 10h, 12h, 24h, 48h, and 72h after treatment administration for both arms.). The study lists 4 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 NCT05083949.

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 27 Jul 2023.