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Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release Compared With Mono Compound Tablets in Healthy Subjects

Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Metformin Extended Release (25 mg/1000 mg) Compared With the Free Combination of Empagliflozin and Metformin Extended Release Tablets in Healthy Subjects Following a High-fat, High-caloric Meal (an Open-label, Randomised, Single Dose, Crossover Trial)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02230995
Enrollment
30
Registered
2014-09-03
Start date
2014-09-30
Completion date
2014-10-31
Last updated
2017-03-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

The purpose of this trial is to demonstrate bioequivalence of a newly developed fixed dose combination (FDC) tablet containing empagliflozin and metformin extended release compared to the free combination of empagliflozin and metformin extended release under fed conditions.

Interventions

DRUGmetformin

single dose of metformin given as tablets

DRUGempagliflozin/metformin

Single dose empagliflozin/metformin given as fixed-dose combination tablet

DRUGempagliflozin

single dose of empagliflozin given as tablet

Sponsors

Eli Lilly and Company
CollaboratorINDUSTRY
Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

\- Healthy male and female subjects

Exclusion criteria

\- Any relevant deviation from healthy condition.

Design outcomes

Primary

MeasureTime frameDescription
AUC0-tz of Empagliflozin in Plasma-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationArea under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)
AUC0-tz of Metformin in Plasma-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationArea under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration
Cmax of Empagliflozin in Plasma-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationMaximum measured concentration of empagliflozin in plasma (Cmax)
Cmax of Metformin in Plasma-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationMaximum measured concentration of the metformin in plasma

Secondary

MeasureTime frameDescription
AUC0-infinity of Empagliflozin in Plasma-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationArea under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity)
AUC0-infinity of Metformin in Plasma-1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administrationArea under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Countries

Germany

Participant flow

Pre-assignment details

This was an open-label, randomised, 2-way crossover trial with 2 treatments (T and R) and 2 treatment sequences (T\_R and R\_T). Trial drug administrations of the 2 single dose treatments were separated by a washout period of at least 7 days.

Participants by arm

ArmCount
Fed 25mg+1000mg FDC/Single
Subjects received in period 1 a single dose of 25 mg empagliflozin/1000 mg metformin HCl XR (1 FDC tablet) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal. 2 treatments separated by a wash-out period of at least 7 days.
15
Fed 25mg+1000mg Single/FDC
Subjects received in period 1 a single dose of 25 mg empagliflozin (1 tablet) together with 1000 mg metformin HCl XR (2 tablets) with 240 mL of water after intake of a high-fat, high-caloric meal, followed in period 2 with a single dose of 25 mg empagliflozin/1000 mg metformin HCl XR (1 FDC tablet) with 240 mL of water after intake of a high-fat, high-caloric meal. 2 treatments separated by a wash-out period of at least 7 days.
15
Total30

Baseline characteristics

CharacteristicFed 25mg+1000mg FDC/SingleFed 25mg+1000mg Single/FDCTotal
Age, Continuous36.60 Years
STANDARD_DEVIATION 9.3
32.00 Years
STANDARD_DEVIATION 9.8
34.30 Years
STANDARD_DEVIATION 9.7
Sex: Female, Male
Female
9 Participants6 Participants15 Participants
Sex: Female, Male
Male
6 Participants9 Participants15 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
5 / 305 / 30
serious
Total, serious adverse events
0 / 300 / 30

Outcome results

Primary

AUC0-tz of Empagliflozin in Plasma

Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz)

Time frame: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Population: PKS set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Fed 25mg+1000mg FDCAUC0-tz of Empagliflozin in Plasma5370 nmol·h/LGeometric Coefficient of Variation 14.9
Fed 25mg+1000mg SingleAUC0-tz of Empagliflozin in Plasma5470 nmol·h/LGeometric Coefficient of Variation 16
p-value: <0.0000190% CI: [96.11, 100.39]ANOVA
Primary

AUC0-tz of Metformin in Plasma

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration

Time frame: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Population: Pharmacokinetic Set (PKS): This analysis set included all treated subjects that provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of the pharmacokinetic endpoints.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Fed 25mg+1000mg FDCAUC0-tz of Metformin in Plasma11000 ng·h/mLGeometric Coefficient of Variation 21.5
Fed 25mg+1000mg SingleAUC0-tz of Metformin in Plasma10800 ng·h/mLGeometric Coefficient of Variation 22.8
p-value: <0.0000190% CI: [98.65, 105.76]ANOVA
Primary

Cmax of Empagliflozin in Plasma

Maximum measured concentration of empagliflozin in plasma (Cmax)

Time frame: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Population: PKS set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Fed 25mg+1000mg FDCCmax of Empagliflozin in Plasma590 nmol/LGeometric Coefficient of Variation 19.9
Fed 25mg+1000mg SingleCmax of Empagliflozin in Plasma597 nmol/LGeometric Coefficient of Variation 19.5
p-value: <0.0000190% CI: [93.51, 104.17]ANOVA
Primary

Cmax of Metformin in Plasma

Maximum measured concentration of the metformin in plasma

Time frame: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Population: PKS set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Fed 25mg+1000mg FDCCmax of Metformin in Plasma1120 ng/mLGeometric Coefficient of Variation 23
Fed 25mg+1000mg SingleCmax of Metformin in Plasma1060 ng/mLGeometric Coefficient of Variation 24.9
p-value: <0.0000190% CI: [100.78, 110.84]ANOVA
Secondary

AUC0-infinity of Empagliflozin in Plasma

Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity)

Time frame: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Population: PKS set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Fed 25mg+1000mg FDCAUC0-infinity of Empagliflozin in Plasma5460 nmol·h/LGeometric Coefficient of Variation 15.1
Fed 25mg+1000mg SingleAUC0-infinity of Empagliflozin in Plasma5550 nmol·h/LGeometric Coefficient of Variation 16.2
90% CI: [96.16, 100.53]ANOVA
Secondary

AUC0-infinity of Metformin in Plasma

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Time frame: -1:00 hour(h) before the drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 5:00h, 6:00h, 7:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h and 72:00h after drug administration

Population: PKS set

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Fed 25mg+1000mg FDCAUC0-infinity of Metformin in Plasma11500 ng*h/mLGeometric Coefficient of Variation 20.2
Fed 25mg+1000mg SingleAUC0-infinity of Metformin in Plasma11000 ng*h/mLGeometric Coefficient of Variation 22.7
90% CI: [101.36, 108.07]ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026