ClinicalTrials.gov
ClinicalTrials.gov Menu

Empa/Lina FDC Food Effect Study (Japan)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02815644
Recruitment Status : Completed
First Posted : June 28, 2016
Results First Posted : August 16, 2018
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Intervention Drug: empagliflozin/linagliptin FDC
Enrollment 22
Recruitment Details  
Pre-assignment Details This is a Open-label, randomised, single-dose, two-sequence, crossover design
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 1: Fed-Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 2: Fasted-Fed)
Hide Arm/Group Description Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after a standard Japanese breakfast in period 1 and after an overnight fast in period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after an overnight fast in period 1 and after a standard Japanese breakfast in period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Period Title: Treatment Period 1 + Washout
Started 11 11
Completed 11 11
Not Completed 0 0
Period Title: Treatment Period 2
Started 11 11
Completed 11 11
Not Completed 0 0
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 1: Fed-Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 2: Fasted-Fed) Total
Hide Arm/Group Description Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after a standard Japanese breakfast in period 1 and after an overnight fast in period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after an overnight fast in period 1 and after a standard Japanese breakfast in period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days Total of all reporting groups
Overall Number of Baseline Participants 11 11 22
Hide Baseline Analysis Population Description
Treated Set (TS): This analysis set included all 22 randomised subjects who were documented to have taken at least 1 dose of trial medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 11 participants 22 participants
29.00  (8.83) 33.73  (9.55) 31.36  (9.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 11 participants 22 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
11
 100.0%
11
 100.0%
22
 100.0%
1.Primary Outcome
Title Cmax for Linagliptin
Hide Description Maximum measured concentration of the analyte in plasma (Cmax) for linagliptin
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Set (PKS): The PKS included all 22 randomised subjects who were documented to have taken at least 1 dose of trial medication under fed or fasted condition without having protocol deviation relevant to the evaluation of relative bioavailability and without experiencing emesis at or before 2 times median tmax.
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
15.1
(50.6%)
8.43
(30.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of linagliptin after food intake compared to while in the fasting state was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R ratio
Estimated Value 55.69
Confidence Interval (2-Sided) 90%
48.22 to 64.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.087
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean.
2.Primary Outcome
Title Cmax for Empagliflozin
Hide Description Maximum measured concentration of the analyte in plasma (Cmax) for empagliflozin
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
1010
(27.1%)
756
(27.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of empagliflozin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R ratio
Estimated Value 74.89
Confidence Interval (2-Sided) 90%
66.27 to 84.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.073
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean
3.Primary Outcome
Title AUC 0-tz for Linagliptin
Hide Description Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration (AUC 0-tz) for linagliptin
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol∙h/L
348
(15.4%)
286
(20.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of linagliptin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R ratio
Estimated Value 82.19
Confidence Interval (2-Sided) 90%
78.38 to 86.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.028
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean
4.Primary Outcome
Title AUC 0-tz for Empagliflozin
Hide Description Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration (AUC 0-tz) for empagliflozin
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol∙h/L
7210
(19.1%)
6200
(20.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of empagliflozin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R ratio
Estimated Value 85.99
Confidence Interval (2-Sided) 90%
83.38 to 88.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.018
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean
5.Secondary Outcome
Title AUC0-infinity for Linagliptin
Hide Description Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for linagliptin
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol∙h/L
597
(20.6%)
526
(33.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of linagliptin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R ratio
Estimated Value 88.13
Confidence Interval (2-Sided) 90%
80.89 to 96.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.051
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean
6.Secondary Outcome
Title AUC0-infinity for Empagliflozin
Hide Description Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for empagliflozin.
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol∙h/L
7270
(19.1%)
6280
(20.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of empagliflozin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R ratio
Estimated Value 86.33
Confidence Interval (2-Sided) 90%
83.61 to 89.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.019
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean
7.Secondary Outcome
Title AUC0-72 for Linagliptin
Hide Description Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours (AUC0-72) for linagliptin
Time Frame 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description:
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
Overall Number of Participants Analyzed 22 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol∙h/L
348
(15.4%)
286
(20.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted), Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Comments Relative bioavailability of linagliptin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: “sequence”, “subjects within sequences”, “period”, and “treatment” (i.e., feeding status). The effect “subjects within sequences” was considered as random, whereas the other effects were considered as fixed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 82.19
Confidence Interval (2-Sided) 90%
78.38 to 86.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.028
Estimation Comments Standard Error of the mean is actually geometric Standard Error of the mean
Time Frame From first drug administration until 7 days thereafter for each treatment arm, up to 8 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Hide Arm/Group Description Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after an overnight fast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after a standard Japanese breakfast in period 1 or period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
All-Cause Mortality
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/22 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)   0/22 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights
Results Point of Contact
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02815644     History of Changes
Other Study ID Numbers: 1275.17
First Submitted: June 24, 2016
First Posted: June 28, 2016
Results First Submitted: September 18, 2017
Results First Posted: August 16, 2018
Last Update Posted: August 16, 2018