CompletedNCT02230995Updated Mar 9, 2017Results posted

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

A Phase 1 interventional study of metformin and empagliflozin/metformin in Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in Germany. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-03-09.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 30
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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.

Conditions studied

Healthy

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Healthy male and female subjects

Exclusion criteria

Exclusion criteria:

Any relevant deviation from healthy condition.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 30 participants (actual)

Study arms

Experimental
Fixed dose combination
Single dose empagliflozin/metformin
Drug: empagliflozin/metformin
Active comparator
Single tablets combination
single doses empagliflozin and metformin
Drug: metformin · Drug: empagliflozin

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

What researchers measure

Primary outcomes

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
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
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
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

Secondary outcomes

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
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

Results

Posted Mar 9, 2017

Participant flow

Period 1 + Washout

Participant flow — Period 1 + Washout
Milestone	Fed 25mg+1000mg FDC/Single	Fed 25mg+1000mg Single/FDC
Started	15	15
Completed	15	15
Not completed	0	0

Period 2 + Washout

Participant flow — Period 2 + Washout
Milestone	Fed 25mg+1000mg FDC/Single	Fed 25mg+1000mg Single/FDC
Started	15	15
Completed	15	15
Not completed	0	0

Outcome measures

PrimaryAUC0-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
Reported as:: Geometric mean · nmol·h/L

AUC0-tz of Empagliflozin in Plasma
nmol·h/L	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
AUC0-tz of Empagliflozin in Plasma	5370 ± 14.9	5470 ± 16.0

Statistical analysis

Fed 25mg+1000mg FDC vs Fed 25mg+1000mg Single · ANOVA · p = <0.00001 · Adjusted gmean ratio: 98.22 · 90% CI 96.11 to 100.39Relative bioavailability of empagliflozin was estimated by the ratios of the adjusted gMean of Fed 25mg+1000mg FDC divided by Fed 25mg+1000mg Single. Standard deviation is actually Intra individual geometric coefficient variation (gCV).

PrimaryAUC0-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
Reported as:: Geometric mean · ng·h/mL

AUC0-tz of Metformin in Plasma
ng·h/mL	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
AUC0-tz of Metformin in Plasma	11000 ± 21.5	10800 ± 22.8

Statistical analysis

Fed 25mg+1000mg FDC vs Fed 25mg+1000mg Single · ANOVA · p = <0.00001 · Adjusted gmean ratio: 102.14 · 90% CI 98.65 to 105.76Relative bioavailability of metformin was estimated by the ratios of the adjusted gMean of Fed 25mg+1000mg FDC divided by Fed 25mg+1000mg Single. Standard deviation is actually Intra individual geometric coefficient variation (gCV).

PrimaryCmax 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
Reported as:: Geometric mean · nmol/L

Cmax of Empagliflozin in Plasma
nmol/L	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
Cmax of Empagliflozin in Plasma	590 ± 19.9	597 ± 19.5

Statistical analysis

Fed 25mg+1000mg FDC vs Fed 25mg+1000mg Single · ANOVA · p = <0.00001 · Adjusted gmean ratio: 98.70 · 90% CI 93.51 to 104.17Relative bioavailability of empagliflozin was estimated by the ratios of the adjusted gMean of Fed 25mg+1000mg FDC divided by Fed 25mg+1000mg Single. Standard deviation is actually Intra individual geometric coefficient variation (gCV).

PrimaryCmax 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
Reported as:: Geometric mean · ng/mL

Cmax of Metformin in Plasma
ng/mL	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
Cmax of Metformin in Plasma	1120 ± 23.0	1060 ± 24.9

Statistical analysis

Fed 25mg+1000mg FDC vs Fed 25mg+1000mg Single · ANOVA · p = <0.00001 · Adjusted gmean ratio: 105.69 · 90% CI 100.78 to 110.84Relative bioavailability of metformin was estimated by the ratios of the adjusted gMean of Fed 25mg+1000mg FDC divided by Fed 25mg+1000mg Single. Standard deviation is actually Intra individual geometric coefficient variation (gCV).

SecondaryAUC0-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
Reported as:: Geometric mean · nmol·h/L

AUC0-infinity of Empagliflozin in Plasma
nmol·h/L	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
AUC0-infinity of Empagliflozin in Plasma	5460 ± 15.1	5550 ± 16.2

Statistical analysis

Fed 25mg+1000mg FDC vs Fed 25mg+1000mg Single · ANOVA · Adjusted gmean ratio: 98.32 · 90% CI 96.16 to 100.53Relative bioavailability of empagliflozin was estimated by ratios of adjusted geometric means (gMean) of Fed 25mg+1000mg FDC divided by Fed 25mg+1000mg Single. Standard deviation is actually Intra individual geometric coefficient variation (gCV).

SecondaryAUC0-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
Reported as:: Geometric mean · ng*h/mL

AUC0-infinity of Metformin in Plasma
ng*h/mL	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
AUC0-infinity of Metformin in Plasma	11500 ± 20.2	11000 ± 22.7

Statistical analysis

Fed 25mg+1000mg FDC vs Fed 25mg+1000mg Single · ANOVA · Adjusted gmean ratio: 104.66 · 90% CI 101.36 to 108.07Relative bioavailability of metformin was estimated by the ratios of the adjusted geometric means (gMean) of Fed 25mg+1000mg FDC divided by Fed 25mg+1000mg Single. Standard deviation is actually Intra individual geometric coefficient variation (gCV).

Adverse events

Collected over From first drug administration up to 13 days after last drug administration, ie., upto 20 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Fed 25mg+1000mg FDC	—	0/30 (0%)	5/30 (16.7%)
Fed 25mg+1000mg Single	—	0/30 (0%)	5/30 (16.7%)

Most frequent other events

Most frequent other events
Event	Fed 25mg+1000mg FDC	Fed 25mg+1000mg Single
HeadacheNervous system disorders	2/30	3/30
NasopharyngitisNervous system disorders	2/30	0/30
DiarrhoeaGastrointestinal disorders	1/30	2/30

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Fed 25mg+1000mg FDC/Single	Fed 25mg+1000mg Single/FDC	Total
Mean	36.60 ± 9.30	32.00 ± 9.80	34.30 ± 9.70

Sex: Female, Male
Sex: Female, Male(Participants)	Fed 25mg+1000mg FDC/Single	Fed 25mg+1000mg Single/FDC	Total
Female	9	6	15
Male	6	9	15

Study locations

1 site

Boehringer Ingelheim Investigational Site
Biberach an der Riss, Germany

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 9, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02230995
Lead sponsor: Boehringer Ingelheim
Collaborators: Eli Lilly and Company
Responsible party: Sponsor
First posted: Sep 3, 2014
Start date: Sep 2014
Primary completion: Oct 2014
Completion: Oct 2014
Results posted: Mar 9, 2017
Last update: Mar 9, 2017

Study contacts

Boehringer Ingelheim

study chair · Boehringer Ingelheim

View the source record on ClinicalTrials.gov ↗

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

Study summary

Conditions studied

In context

Lead sponsor

Who can participate

✓Inclusion criteria

✕Exclusion criteria

Study design

Study arms

Interventions

What researchers measure

Primary outcomes

Secondary outcomes

Results

Participant flow

Outcome measures

Adverse events

Baseline characteristics

Study locations

Updates

Registry details

Key details

Study contacts

Not currently enrolling

Follow this study

Discussion

Other studies from this sponsor

Inclusion criteria

Exclusion criteria