Empa/Lina FDC Food Effect Study (Japan)
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT02815644
Collaborator
(none)
22
1
1
2.7
8.2
Study Details
Study Description
Brief Summary
The trial will be performed as an open-label, randomised, single-dose, two-sequence crossover design for the assessment of effect of food on bioavailability of empagliflozin / linagliptin fixed dose combination (FDC) tablet.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
22 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Investigation of the Effect of Food on the Bioavailability of Empagliflozin / Linagliptin Fixed Dose Combination Tablet in an Open, Randomised, Single Dose, Two Way Cross-over Study in Healthy Japanese Male Subjects
Actual Study Start Date
:
Jul 15, 2016
Actual Primary Completion Date
:
Oct 5, 2016
Actual Study Completion Date
:
Oct 5, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: empagliflozin/linagliptin FDC empagliflozin/linagliptin fixed-dose combination (FDC) film-coated tablet |
Drug: empagliflozin/linagliptin FDC
empagliflozin/linagliptin fixed-dose combination (FDC) film-coated tablet
|
Outcome Measures
Primary Outcome Measures
- Cmax for Linagliptin [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.]
Maximum measured concentration of the analyte in plasma (Cmax) for linagliptin
- Cmax for Empagliflozin [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.]
Maximum measured concentration of the analyte in plasma (Cmax) for empagliflozin
- AUC 0-tz for Linagliptin [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.]
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
- AUC 0-tz for Empagliflozin [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.]
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
Secondary Outcome Measures
- AUC0-infinity for Linagliptin [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.]
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for linagliptin
- AUC0-infinity for Empagliflozin [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.]
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for empagliflozin.
- AUC0-72 for Linagliptin [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.]
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours (AUC0-72) for linagliptin
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 45 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
-
Healthy male subjects age >=20 and <=45 years; body weight: >=50 kg and <=80 kg; body mass index: >=18.0 and <=25.0 kg/m2
-
Without any clinically significant findings and complications on the basis of a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature)
-
Signed and dated written informed consent prior to admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation
Exclusion criteria:
-
Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance
-
Further exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SOUSEIKAI Sumida Hospital | Tokyo, Sumida-ku | Japan | 133-0004 |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02815644
Other Study ID Numbers:
- 1275.17
First Posted:
Jun 28, 2016
Last Update Posted:
Aug 16, 2018
Last Verified:
Oct 1, 2017
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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) |
|---|---|---|
| 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 1 + Washout | ||
| STARTED | 11 | 11 |
| COMPLETED | 11 | 11 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 1: Fed-Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 2: Fasted-Fed) | Total |
|---|---|---|---|
| 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 Participants | 11 | 11 | 22 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
29.00
(8.83)
|
33.73
(9.55)
|
31.36
(9.30)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
11
100%
|
11
100%
|
22
100%
|
Outcome Measures
| Title | Cmax for Linagliptin |
|---|---|
| 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. |
Outcome Measure Data
| 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) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
15.1
(50.6)
|
8.43
(30.3)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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. | |
| Title | Cmax for Empagliflozin |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
1010
(27.1)
|
756
(27.3)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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 | |
| Title | AUC 0-tz for Linagliptin |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol∙h/L] |
348
(15.4)
|
286
(20.5)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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 | |
| Title | AUC 0-tz for Empagliflozin |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol∙h/L] |
7210
(19.1)
|
6200
(20.6)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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 | |
| Title | AUC0-infinity for Linagliptin |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol∙h/L] |
597
(20.6)
|
526
(33.4)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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 | |
| Title | AUC0-infinity for Empagliflozin |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol∙h/L] |
7270
(19.1)
|
6280
(20.4)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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 | |
| Title | AUC0-72 for Linagliptin |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS |
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) |
|---|---|---|
| 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 |
| Measure Participants | 22 | 22 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol∙h/L] |
348
(15.4)
|
286
(20.5)
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| 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 | |
Adverse Events
| Time Frame | From first drug administration until 7 days thereafter for each treatment arm, up to 8 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | 0/22 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted) | Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | 0/22 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02815644
Other Study ID Numbers:
- 1275.17
First Posted:
Jun 28, 2016
Last Update Posted:
Aug 16, 2018
Last Verified:
Oct 1, 2017