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

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:

Drug Information available for: Linagliptin Empagliflozin

U.S. FDA Resources

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 (Adult)
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:

Related Info This link exits the ClinicalTrials.gov site


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:


Empagliflozin Linagliptin Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones	Hormones, Hormone Substitutes, and Hormone Antagonists Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2016