Rel. BA of Empagliflozin (BI 10773)/Linagliptin FDC Tbl, Comparison With Mono-components, With a Second FDC Tablet and Influence of Food

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01189201
First received: August 25, 2010
Last updated: March 10, 2015
Last verified: March 2015
  Purpose

The primary objective of the current study is to investigate the relative bioavailability of BI 10773 / linagliptin fixed dose combination tablet (formulation A1, Treatment A, Test) compared to BI 10773 given in free combination with linagliptin (Treatment B, Reference), both in the fasting state. All 42 subjects entered are planned to be included in this comparison.

The secondary objective is to investigate the relative bioavailability of BI 10773 / linagliptin fixed dose combination tablet after administration of a standardised high fat, high caloric meal (formulation A1, Treatment C, Test) compared to BI 10773 / linagliptin fixed dose combination in the fasting state (formulation A1,Treatment A, Reference). Of the 42 subjects entered 18 subjects are planned to be included in this comparison.

An additional objective is to investigate the relative bioavailability of a second formulation of the fixed dose combination tablet of BI 10773 / linagliptin (formulation A3,Treatment D, Test) compared to BI 10773 / linagliptin fixed dose combination tablet (formulation A1,Treatment A, Reference). Of the 42 subjects entered 24 subjects are planned to be included in this comparison.


Condition Intervention Phase
Healthy
Drug: BI 10773/linagliptin
Drug: BI 10773/linagliptin SID
Drug: BI 10773/linagliptin FDC
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Relative Bioavailability Investigations of a 25 mg BI 10773 / 5 mg Linagliptin Fixed Dose Combination (FDC) Tablet (Formulation A1) Including the Comparison With Its Mono-components, the Comparison With a Second FDC Tablet (Formulation A3), and the Investigation of Food (an Open-label, Randomised, Single Dose, Crossover, Phase I Trial in Healthy Male and Female Volunteers)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Empagliflozin: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin: Area Under the Curve 0 to 72 Hours (AUC0-72) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Maximum measured concentration of empagliflozin (empa) in plasma.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Maximum measured concentration of linagliptin in plasma.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin Fed vs Fasted: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Maximum measured concentration of empagliflozin (empa) in plasma, comparing fed with fasted.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin Fed vs Fasted: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin Fed vs Fasted: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Maximum measured concentration of linagliptin in plasma.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin Fed vs Fasted: Area Under the Curve 0 to 72 Hours (AUC0-72) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin Formulation Comparison: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Maximum measured concentration of empagliflozin (empa) in plasma.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin Formulation Comparison: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin Formulation Comparison: Maximum Measured Concentration (Cmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Maximum measured concentration of linagliptin in plasma.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin Formulation Comparison: Area Under the Curve 0 to 72 Hours (AUC0-72) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours.

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.



Secondary Outcome Measures:
  • Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]
    Time from last dosing to the maximum measured concentration of empagliflozin (empa) in plasma.

  • Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]
    Time from last dosing to the maximum measured concentration of linagliptin in plasma

  • Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Empagliflozin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: Yes ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Linagliptin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) [ Time Frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration ] [ Designated as safety issue: No ]

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

    In this endpoint, the "measured values" show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.


  • Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator [ Time Frame: Drug administration until next treatment period/end-of-study examination, up to 36 days ] [ Designated as safety issue: No ]
    Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Time frame for adverse event was until the end-of-study examination.


Enrollment: 42
Study Start Date: August 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 10773/linagliptin FDC SID
medium single dose ofBI 10773/linagliptin FDC (Formulation A1)
Drug: BI 10773/linagliptin
medium single dose of BI 10773/linagliptin FDC (Formulation A1)
Experimental: BI 10773/linagliptin SID
medium single dose of mono components BI 10773/linagliptin
Drug: BI 10773/linagliptin SID
medium single dose of mono components BI 10773/linagliptin
Experimental: BI 10773/linagliptin FDC
medium single dose of BI 10773/linagliptin FDC (Formulation A1) after high fat, high caloric meal
Drug: BI 10773/linagliptin FDC
medium single dose of BI 10773/linagliptin FDC (Formulation A1) after high fat, high caloric meal
Experimental: BI 10773/linagliptin
medium single dose of BI 10773/linagliptin FDC (Formulation A3)
Drug: BI 10773/linagliptin
medium single dose of BI 10773/linagliptin FDC (Formulation A3)

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

healthy male and female subjects

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01189201

Locations
Germany
1275.3.1 Boehringer Ingelheim Investigational Site
Biberach, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01189201     History of Changes
Other Study ID Numbers: 1275.3, 2010-019211-38
Study First Received: August 25, 2010
Results First Received: March 10, 2015
Last Updated: March 10, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Linagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on May 21, 2015