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CompletedNCT02084056Updated Aug 4, 2016Results posted

Bioequivalence of a FDC Tablet of Linagliptin/Metformin (2.5mg/1000mg) Extended Release in Healthy Subjects.

A Phase 1 interventional study of Linagliptin and 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 2016-08-04.

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

Phase
Phase 1
Study type
Interventional
Enrollment
74
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

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

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,297 studies on the registry; 56 are open to participants now.

Of its 166 completed or terminated interventional studies of FDA-regulated products, 121 (73%) have results posted.

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

04

Who can participate

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

- Healthy male or female subjects

Exclusion criteria

Exclusion criteria:

- Any relevant deviation from healthy condition

05

Study design

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

Study arms

  • Experimental
    FDC first, fasted

    Linagliptin/Metformin FDC followed by single tablets of linagliptin and metformin, fasted

    Drug: Linagliptin · Drug: Metformin · Drug: Linagliptin/Metformin FDC

  • Experimental
    Single tablets first, fasted

    single tablets of linagliptin and metformin followed by Linagliptin/Metformin FDC, fasted

    Drug: Linagliptin · Drug: Metformin · Drug: Linagliptin/Metformin FDC

  • Experimental
    FDC first, fed

    Linagliptin/Metformin FDC followed by single tablets of linagliptin and metformin, fed

    Drug: Linagliptin · Drug: Metformin · Drug: Linagliptin/Metformin FDC

  • Experimental
    Single tablets first, fed

    single tablets of linagliptin and metformin followed by Linagliptin/Metformin FDC, fed

    Drug: Linagliptin · Drug: Metformin · Drug: Linagliptin/Metformin FDC

Interventions

06

What researchers measure

Primary outcomes

  1. Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)

    AUC 0-72 (area under the concentration-time curve of Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

    Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

  2. Maximum Measured Concentration of Linagliptin in Plasma (Cmax)

    Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

    Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

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

    AUC 0-tz (Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

    Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

  4. Cmax of Metformin in Plasma

    Cmax (maximum measured concentration of Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

    Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

Secondary outcomes

  1. Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)

    AUC0-inf (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity) for Linagliptin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

    Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

  2. AUC0-inf of Metformin in Plasma

    AUC0-inf(area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity) for Metformin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

    Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

07

Results

Posted Aug 4, 2016

Participant flow

This study was conducted in two parts. Part 1: Fasting study Part 2: Fed Study

Treatment Period 1 (4 Days)
Participant flow — Treatment Period 1 (4 Days)
MilestoneFDC 2000 Fasted / L+M 2000 FastedL+M 2000 Fasted / FDC 2000 FastedFDC 2000 Fed / L+M 2000 FedL+M 2000 Fed / FDC 2000 Fed
Started283088
Completed273088
Not completed1000
Withdrew: Withdrawal by subject1000
Washout Period 1 (35 Days)
Participant flow — Washout Period 1 (35 Days)
MilestoneFDC 2000 Fasted / L+M 2000 FastedL+M 2000 Fasted / FDC 2000 FastedFDC 2000 Fed / L+M 2000 FedL+M 2000 Fed / FDC 2000 Fed
Started273088
Completed263088
Not completed1000
Withdrew: Withdrawal by subject1000
Treatment Period 2 (4 Days)
Participant flow — Treatment Period 2 (4 Days)
MilestoneFDC 2000 Fasted / L+M 2000 FastedL+M 2000 Fasted / FDC 2000 FastedFDC 2000 Fed / L+M 2000 FedL+M 2000 Fed / FDC 2000 Fed
Started263088
Completed263088
Not completed0000

Outcome measures

PrimaryArea Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)

AUC 0-72 (area under the concentration-time curve of Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

Time frame:
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Reported as:
Geometric mean · nmol*h/L
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)
nmol*h/LL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)278.460 ± 9.1288.709 ± 9.1264.509 ± 12.7268.814 ± 12.7
Statistical analysis
  • L+M 2000 Fasted vs FDC 2000 Fasted · ANOVA · p = <0.0001 · Adjusted geometric means ratio: 103.68 · 90% CI 100.703 to 106.747Ratio of (FDC 2000 fasted/ L+M 2000 fasted)
  • L+M 2000 Fed vs FDC 2000 Fed · ANOVA · p = 0.0003 · Adjusted geometric means ratio: 101.63 · 90% CI 93.721 to 110.202Ratio of (FDC 2000 fed/ L+M 2000 fed)
PrimaryMaximum Measured Concentration of Linagliptin in Plasma (Cmax)

Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

Time frame:
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Reported as:
Geometric mean · nmol/L
Maximum Measured Concentration of Linagliptin in Plasma (Cmax)
nmol/LL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
Maximum Measured Concentration of Linagliptin in Plasma (Cmax)8.274 ± 19.69.480 ± 19.66.729 ± 20.16.613 ± 20.1
Statistical analysis
  • L+M 2000 Fasted vs FDC 2000 Fasted · ANOVA · p = 0.0113 · Adjusted geometric means ratio: 114.58 · 90% CI 107.687 to 121.908Ratio of (FDC 2000 fasted/ L+M 2000 fasted)
  • L+M 2000 Fed vs FDC 2000 Fed · ANOVA · p = 0.0064 · Adjusted geometric means ratio: 98.28 · 90% CI 86.543 to 111.609Ratio of (FDC 2000 fed/ L+M 2000 fed)
PrimaryArea Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

AUC 0-tz (Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

Time frame:
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Reported as:
Geometric mean · ng*h/mL
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
ng*h/mLL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)12028.27 ± 17.611601.19 ± 17.620411.01 ± 11.719952.61 ± 11.7
Statistical analysis
  • L+M 2000 Fasted vs FDC 2000 Fasted · ANOVA · p = <0.0001 · Adjusted geometric means ratio: 96.45 · 90% CI 91.23 to 101.97Ratio of (FDC 2000 fasted/ L+M 2000 fasted)
  • L+M 2000 Fed vs FDC 2000 Fed · ANOVA · p = 0.0002 · Adjusted geometric means ratio: 97.75 · 90% CI 90.47 to 105.63Ratio of (FDC 2000 fed/ L+M 2000 fed)
PrimaryCmax of Metformin in Plasma

Cmax (maximum measured concentration of Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

Time frame:
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Reported as:
Geometric mean · ng/mL
Cmax of Metformin in Plasma
ng/mLL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
Cmax of Metformin in Plasma1516.558 ± 19.91485.642 ± 19.91571.040 ± 13.81662.954 ± 13.8
Statistical analysis
  • L+M 2000 Fasted vs FDC 2000 Fasted · ANOVA · p = <0.0001 · Adjusted geometric means ratio: 97.96 · 90% CI 92.046 to 104.257Ratio of (FDC 2000 fasted/ L+M 2000 fasted)
  • L+M 2000 Fed vs FDC 2000 Fed · ANOVA · p = 0.0030 · Adjusted geometric means ratio: 105.85 · 90% CI 96.705 to 115.861Ratio of (FDC 2000 fed/ L+M 2000 fed)
SecondaryArea Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)

AUC0-inf (area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity) for Linagliptin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

Time frame:
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Reported as:
Geometric mean · nmol*h/L
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
nmol*h/LL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)457.780 ± 15.8473.704 ± 15.8445.884 ± 16.7451.888 ± 16.7
Statistical analysis
  • L+M 2000 Fasted vs FDC 2000 Fasted · ANOVA · p = <0.0001 · Adjusted geometric means ratio: 103.48 · 90% CI 98.426 to 108.790Ratio of (FDC 2000 fasted/ L+M 2000 fasted)
  • L+M 2000 Fed vs FDC 2000 Fed · ANOVA · p = 0.0019 · Adjusted geometric means ratio: 101.35 · 90% CI 91.130 to 112.708Ratio of (FDC 2000 fed/ L+M 2000 fed)
SecondaryAUC0-inf of Metformin in Plasma

AUC0-inf(area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity) for Metformin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

Time frame:
1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Reported as:
Geometric mean · ng*h/mL
AUC0-inf of Metformin in Plasma
ng*h/mLL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
AUC0-inf of Metformin in Plasma12736.87 ± 19.712162.37 ± 19.720721.20 ± 11.920346.34 ± 11.9
Statistical analysis
  • L+M 2000 Fasted vs FDC 2000 Fasted · ANOVA · p = <0.0001 · Adjusted geometric means ratio: 95.49 · 90% CI 89.73 to 101.62Ratio of (FDC 2000 fasted/ L+M 2000 fasted)
  • L+M 2000 Fed vs FDC 2000 Fed · ANOVA · p = 0.0002 · Adjusted geometric means ratio: 98.19 · 90% CI 90.73 to 106.27Ratio of (FDC 2000 fed/ L+M 2000 fed)

Adverse events

Collected over From the first drug administration for at least 7 days after the last drug administration, up to 47 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
L+M 2000 Fasted—0/56 (0%)20/56 (35.7%)
FDC 2000 Fasted—0/58 (0%)24/58 (41.4%)
L+M 2000 Fed—0/16 (0%)8/16 (50%)
FDC 2000 Fed—0/16 (0%)5/16 (31.3%)
Most frequent other events
Showing 10 of 13
Most frequent other events
EventL+M 2000 FastedFDC 2000 FastedL+M 2000 FedFDC 2000 Fed
DiarrhoeaGastrointestinal disorders3/565/584/161/16
HeadacheNervous system disorders11/569/583/161/16
Abdominal painGastrointestinal disorders3/566/582/161/16
NauseaGastrointestinal disorders2/565/582/160/16
RetchingGastrointestinal disorders0/560/581/160/16
VomitingGastrointestinal disorders1/561/581/161/16
DiscomfortGeneral disorders0/560/580/161/16
Influenza like illnessGeneral disorders0/560/581/160/16
NasopharyngitisInfections and infestations1/562/581/160/16
Muscle tightnessMusculoskeletal and connective tissue disorders0/560/581/160/16

Baseline characteristics

Treated set: All randomised subjects who received 1 dose of trial medication were included in the treated set.

Age, Continuous
Age, Continuous(years)FDC 2000 Fasted or L+M 2000 FastedFDC 2000 Fed or L+M 2000 FedTotal
Mean33.1 ± 9.832.6 ± 8.233.0 ± 9.4
Sex: Female, Male
Sex: Female, Male(Participants)FDC 2000 Fasted or L+M 2000 FastedFDC 2000 Fed or L+M 2000 FedTotal
Female38745
Male20929
08

Study locations

1 site
  • 1288.11.1 Boehringer Ingelheim Investigational Site
    Biberach, Germany
09

References and documents

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 4, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02084056
Lead sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
Responsible party
Sponsor
First posted
Mar 11, 2014
Start date
Apr 2014
Primary completion
Jul 2014
Completion
Jul 2014
Results posted
Aug 4, 2016
Last update
Aug 4, 2016

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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