Equivalence of Resorption of Empagliflozin/Metformin Administered as Combination Tablet Compared With Empagliflozin/Metformin as Single Tablets Administered Together
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT01811953
Collaborator
(none)
48
1
6
2
24
Study Details
Study Description
Brief Summary
Bioequivalence of an empagliflozin/metformin (FDC) tablet compared with single tablets of two strength of empagliflozin and metformin (Part I) under fasted and under fed conditions and bioequivalence of empagliflozin/metformin (FDC) tablet compared with single tablets empagliflozin and metformin under fed conditions (Part II).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
48 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Bioequivalence of Empagliflozin/Metformin Fixed Dose Combination Tablets Compared to Single Tablets Administered Together in Healthy Male and Female Volunteers Under Fed and Fasted Conditions (an Open-label, Randomised, Single-dose, Crossover Study)
Study Start Date
:
Mar 1, 2013
Actual Primary Completion Date
:
May 1, 2013
Actual Study Completion Date
:
May 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Empagliflozin/Metformin (T) fixed-dose-combination tablet, oral with 240 ml water under fasted conditions |
Drug: Empagliflozin/Metformin
medium dose of Empagliflozin oral administration
|
| Experimental: 2 Empagliflozin/Metformin (T) fixed-dose-combination tablet, oral with 240 ml water under fed conditions |
Drug: Empagliflozin/Metformin
medium dose of Empagliflozin oral administration
|
| Experimental: 3 Empagliflozin + Metformin (R) tablets, oral with 240 ml water under fasted conditions |
Drug: Empagliflozin
medium dose oral administration
Drug: Metformin
oral administration
|
| Experimental: 4 Empagliflozin + Metformin (R) tablets, oral with 240 ml water under fed conditions |
Drug: Empagliflozin
medium dose oral administration
Drug: Metformin
oral administration
|
| Experimental: 5 Empagliflozin/Metformin (T) fixed-dose-combination tablet, oral with 240 ml water under fed conditions |
Drug: Empagliflozin/Metformin
low dose of Empagliflozin
|
| Experimental: 6 Empagliflozin + Metformin (R) tablets, oral with 240 ml water under fed conditions |
Drug: Empagliflozin
low dose of Empagliflozin oral administration
Drug: Metformin
oral administration
|
Outcome Measures
Primary Outcome Measures
- Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Empagliflozin [1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration]
AUC0-inf: area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for Empagliflozin
- Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Metformin [1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration]
AUC0-inf: area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for Metformin
- Maximum Measured Concentration of the Analyte in Plasma, Empagliflozin [1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration]
Cmax: maximum measured concentration of the analyte in plasma for Empagliflozin
- Maximum Measured Concentration of the Analyte in Plasma, Metformin [1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration]
Cmax: maximum measured concentration of the analyte in plasma for Metformin
Secondary Outcome Measures
- Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point, Empagliflozin [1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration]
AUC0-tz: area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point for Empagliflozin
- Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point, Metformin [1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration]
AUC0-tz: area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point for Metformin
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion criteria:
- Healthy male and female subjects
Exclusion criteria:
- Any relevant deviation from healthy conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1276.8.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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:
NCT01811953
Other Study ID Numbers:
- 1276.8
- 2012-005156-42
First Posted:
Mar 15, 2013
Last Update Posted:
Jul 27, 2015
Last Verified:
Jun 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Emp/Met Fasted / Emp+Met Fasted / Emp/Met Fed / Emp+Met Fed | Emp/Met Fed / Emp+Met Fed / Emp/Met Fasted / Emp+Met Fasted | Emp+Met Fasted / Emp/Met Fasted / Emp+Met Fed / Emp/Met Fed | Emp+Met Fed / Emp/Met Fed / Emp+Met Fasted / Emp/Met Fasted | Low Dose Emp: Emp/Met / Emp+Met | Low Dose Emp: Emp+Met / Emp/Met |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination (FDC) tablet under fasted conditions first; then free dose combination tablets under fasted conditions; then FDC tablet under fed conditions; then free dose combination tablets under fed conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | fixed-dose-combination (FDC) tablet under fed conditions first; then free dose combination tablets under fed conditions; then FDC tablet under fasted conditions; then free dose combination tablets under fasted conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | free dose combination tablets under fasted conditions first; then fixed-dose-combination (FDC) tablet under fasted conditions; then free dose combination tablets under fed conditions; then FDC tablet under fed conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | free dose combination tablets under fed conditions first; then FDC tablet under fed conditions; then free dose combination tablets under fasted conditions; then fixed-dose-combination (FDC) tablet under fasted conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | fixed-dose-combination tablet under fed conditions first; then free dose combination tablets under fed conditions Empagliflozin (Emp): 5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | free dose combination tablets under fed conditions first; then fixed-dose-combination tablet under fed conditions Empagliflozin (Emp): 5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) |
| Period Title: Overall Study | ||||||
| STARTED | 6 | 6 | 6 | 6 | 12 | 12 |
| COMPLETED | 6 | 6 | 6 | 5 | 11 | 11 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Emp/Met Fasted / Emp+Met Fasted / Emp/Met Fed / Emp+Met Fed | Emp/Met Fed / Emp+Met Fed / Emp/Met Fasted / Emp+Met Fasted | Emp+Met Fasted / Emp/Met Fasted / Emp+Met Fed / Emp/Met Fed | Emp+Met Fed / Emp/Met Fed / Emp+Met Fasted / Emp/Met Fasted | Low Dose Emp: Emp/Met / Emp+Met | Low Dose Emp: Emp+Met / Emp/Met | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination (FDC) tablet under fasted conditions first; then free dose combination tablets under fasted conditions; then FDC tablet under fed conditions; then free dose combination tablets under fed conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | fixed-dose-combination (FDC) tablet under fed conditions first; then free dose combination tablets under fed conditions; then FDC tablet under fasted conditions; then free dose combination tablets under fasted conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | free dose combination tablets under fasted conditions first; then fixed-dose-combination (FDC) tablet under fasted conditions; then free dose combination tablets under fed conditions; then FDC tablet under fed conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | free dose combination tablets under fed conditions first; then FDC tablet under fed conditions; then free dose combination tablets under fasted conditions; then fixed-dose-combination (FDC) tablet under fasted conditions Empagliflozin (Emp): 12.5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | fixed-dose-combination tablet under fed conditions first; then free dose combination tablets under fed conditions Empagliflozin (Emp): 5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | free dose combination tablets under fed conditions first; then fixed-dose-combination tablet under fed conditions Empagliflozin (Emp): 5 mg; Metformin (Met): 1000 mg (oral with 240 ml water) | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 12 | 12 | 48 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
33.5
(6.7)
|
26.5
(9.7)
|
28.5
(9.5)
|
33.2
(7.1)
|
32.8
(9.8)
|
32.3
(9.6)
|
31.5
(8.9)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
3
50%
|
3
50%
|
1
16.7%
|
4
66.7%
|
7
58.3%
|
7
58.3%
|
25
52.1%
|
| Male |
3
50%
|
3
50%
|
5
83.3%
|
2
33.3%
|
5
41.7%
|
5
41.7%
|
23
47.9%
|
Outcome Measures
| Title | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Empagliflozin |
|---|---|
| Description | AUC0-inf: area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for Empagliflozin |
| Time Frame | 1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic set (PKS): included all subjects of the TS who provided at least one observation for at least one primary PK endpoint and who did not have a protocol violation relevant to the evaluation of Pharmacokinetics. |
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration |
| Measure Participants | 23 | 24 | 24 | 22 | 22 | 23 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
2810
(19.3)
|
2580
(20.4)
|
2760
(20.0)
|
2570
(20.7)
|
988
(16.2)
|
927
(18.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Empagliflozin/Metformin (T), 3 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 102.55 | |
| Confidence Interval |
(2-Sided) 90% 99.531 to 105.653 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.017 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '1 Empagliflozin/Metformin (T)' divided by the geometric mean of '3 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Empagliflozin/Metformin (T), 4 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 98.88 | |
| Confidence Interval |
(2-Sided) 90% 94.879 to 103.059 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.024 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '2 Empagliflozin/Metformin (T)' divided by the geometric mean of '4 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 5 Empagliflozin/Metformin (T), 6 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 106.00 | |
| Confidence Interval |
(2-Sided) 90% 102.728 to 109.386 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.018 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '5 Empagliflozin/Metformin (T)' divided by the geometric mean of '6 Empagliflozin + Metformin (R)'. | |
| Title | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity, Metformin |
|---|---|
| Description | AUC0-inf: area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for Metformin |
| Time Frame | 1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS: included all subjects of the TS who provided at least one observation for at least one primary PK endpoint and who did not have a protocol violation relevant to the evaluation of Pharmacokinetics. |
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration |
| Measure Participants | 23 | 24 | 24 | 22 | 21 | 23 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
10400
(23.0)
|
9220
(26.4)
|
11000
(26.8)
|
9140
(22.9)
|
9080
(32.7)
|
9060
(26.7)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Empagliflozin/Metformin (T), 3 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 96.13 | |
| Confidence Interval |
(2-Sided) 90% 91.25 to 101.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '1 Empagliflozin/Metformin (T)' divided by the geometric mean of '3 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Empagliflozin/Metformin (T), 4 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 99.34 | |
| Confidence Interval |
(2-Sided) 90% 92.56 to 106.62 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.04 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '2 Empagliflozin/Metformin (T)' divided by the geometric mean of '4 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 5 Empagliflozin/Metformin (T), 6 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean difference |
| Estimated Value | 100.81 | |
| Confidence Interval |
(2-Sided) 90% 95.74 to 106.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '5 Empagliflozin/Metformin (T)' divided by the geometric mean of '6 Empagliflozin + Metformin (R)'. | |
| Title | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point, Empagliflozin |
|---|---|
| Description | AUC0-tz: area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point for Empagliflozin |
| Time Frame | 1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS: included all subjects of the TS who provided at least one observation for at least one primary PK endpoint and who did not have a protocol violation relevant to the evaluation of Pharmacokinetics. |
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration |
| Measure Participants | 23 | 24 | 24 | 22 | 22 | 23 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol*h/L] |
2770
(19.2)
|
2530
(20.1)
|
2720
(20.0)
|
2510
(20.2)
|
962
(16.3)
|
903
(18.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Empagliflozin/Metformin (T), 3 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 102.33 | |
| Confidence Interval |
(2-Sided) 90% 99.315 to 105.430 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.017 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '1 Empagliflozin/Metformin (T)' divided by the geometric mean of '3 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Empagliflozin/Metformin (T), 4 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 98.82 | |
| Confidence Interval |
(2-Sided) 90% 94.784 to 103.037 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.024 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '2 Empagliflozin/Metformin (T)' divided by the geometric mean of '4 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 5 Empagliflozin/Metformin (T), 6 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 105.98 | |
| Confidence Interval |
(2-Sided) 90% 102.730 to 109.329 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.018 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '5 Empagliflozin/Metformin (T)' divided by the geometric mean of '6 Empagliflozin + Metformin (R)'. | |
| Title | Maximum Measured Concentration of the Analyte in Plasma, Empagliflozin |
|---|---|
| Description | Cmax: maximum measured concentration of the analyte in plasma for Empagliflozin |
| Time Frame | 1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS: included all subjects of the TS who provided at least one observation for at least one primary PK endpoint and who did not have a protocol violation relevant to the evaluation of Pharmacokinetics. |
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration |
| Measure Participants | 23 | 24 | 24 | 22 | 22 | 23 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
379
(23.7)
|
276
(24.8)
|
375
(27.3)
|
258
(28.5)
|
108
(16.9)
|
103
(14.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Empagliflozin/Metformin (T), 3 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 102.12 | |
| Confidence Interval |
(2-Sided) 90% 96.255 to 108.351 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.035 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '1 Empagliflozin/Metformin (T)' divided by the geometric mean of '3 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Empagliflozin/Metformin (T), 4 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | 0.0082 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 106.52 | |
| Confidence Interval |
(2-Sided) 90% 95.863 to 118.353 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.063 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '2 Empagliflozin/Metformin (T)' divided by the geometric mean of '4 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 5 Empagliflozin/Metformin (T), 6 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 104.352 | |
| Confidence Interval |
(2-Sided) 90% 99.152 to 110.224 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.031 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '5 Empagliflozin/Metformin (T)' divided by the geometric mean of '6 Empagliflozin + Metformin (R)'. | |
| Title | Maximum Measured Concentration of the Analyte in Plasma, Metformin |
|---|---|
| Description | Cmax: maximum measured concentration of the analyte in plasma for Metformin |
| Time Frame | 1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS: included all subjects of the TS who provided at least one observation for at least one primary PK endpoint and who did not have a protocol violation relevant to the evaluation of Pharmacokinetics. |
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration |
| Measure Participants | 23 | 24 | 24 | 22 | 21 | 23 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
1580
(26.9)
|
1160
(17.8)
|
1680
(25.8)
|
1180
(21.2)
|
1180
(23.8)
|
1150
(24.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Empagliflozin/Metformin (T), 3 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 94.87 | |
| Confidence Interval |
(2-Sided) 90% 88.931 to 101.210 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.038 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '1 Empagliflozin/Metformin (T)' divided by the geometric mean of '3 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Empagliflozin/Metformin (T), 4 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 97.97 | |
| Confidence Interval |
(2-Sided) 90% 92.339 to 103.935 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.035 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '2 Empagliflozin/Metformin (T)' divided by the geometric mean of '4 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 5 Empagliflozin/Metformin (T), 6 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 102.95 | |
| Confidence Interval |
(2-Sided) 90% 97.166 to 109.082 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.034 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '5 Empagliflozin/Metformin (T)' divided by the geometric mean of '6 Empagliflozin + Metformin (R)'. | |
| Title | Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point, Metformin |
|---|---|
| Description | AUC0-tz: area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point for Metformin |
| Time Frame | 1 hour (h) before first drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30 min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
Outcome Measure Data
| Analysis Population Description |
|---|
| PKS: included all subjects of the TS who provided at least one observation for at least one primary PK endpoint and who did not have a protocol violation relevant to the evaluation of Pharmacokinetics. |
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) |
|---|---|---|---|---|---|---|
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration |
| Measure Participants | 23 | 24 | 24 | 22 | 21 | 23 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
10100
(21.3)
|
8960
(24.5)
|
10700
(24.1)
|
8930
(22.5)
|
8870
(30.8)
|
8850
(26.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 Empagliflozin/Metformin (T), 3 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 94.89 | |
| Confidence Interval |
(2-Sided) 90% 89.80 to 100.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '1 Empagliflozin/Metformin (T)' divided by the geometric mean of '3 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 2 Empagliflozin/Metformin (T), 4 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 99.31 | |
| Confidence Interval |
(2-Sided) 90% 92.14 to 107.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.04 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '2 Empagliflozin/Metformin (T)' divided by the geometric mean of '4 Empagliflozin + Metformin (R)'. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 5 Empagliflozin/Metformin (T), 6 Empagliflozin + Metformin (R) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | The assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMean), test/reference, for the primary endpoints using an acceptance range of 80.00 to 125.00%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 100.74 | |
| Confidence Interval |
(2-Sided) 90% 95.77 to 105.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | The geometric mean ratio was calculated as the geometric mean of '5 Empagliflozin/Metformin (T)' divided by the geometric mean of '6 Empagliflozin + Metformin (R)'. | |
Adverse Events
| Time Frame | From first trial medication intake until next intake or the end-of-trial visit, 10 days | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Evens were reported for all patients who received the specific treatment. | |||||||||||
| Arm/Group Title | 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) | ||||||
| Arm/Group Description | fixed-dose-combination tablet, oral with 240 ml water under fasted conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: medium dose of Empagliflozin oral administration | tablets, oral with 240 ml water under fasted conditions Empagliflozin: medium dose oral administration Metformin: oral administration | tablets, oral with 240 ml water under fed conditions Empagliflozin: medium dose oral administration Metformin: oral administration | fixed-dose-combination tablet, oral with 240 ml water under fed conditions Empagliflozin/Metformin: low dose of Empagliflozin | tablets, oral with 240 ml water under fed conditions Empagliflozin: low dose of Empagliflozin oral administration Metformin: oral administration | ||||||
All Cause Mortality |
||||||||||||
| 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 0/24 (0%) | 0/24 (0%) | 0/24 (0%) | 0/23 (0%) | 0/23 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| 1 Empagliflozin/Metformin (T) | 2 Empagliflozin/Metformin (T) | 3 Empagliflozin + Metformin (R) | 4 Empagliflozin + Metformin (R) | 5 Empagliflozin/Metformin (T) | 6 Empagliflozin + Metformin (R) | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/23 (26.1%) | 6/24 (25%) | 4/24 (16.7%) | 6/24 (25%) | 9/23 (39.1%) | 10/23 (43.5%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Diarrhoea | 2/23 (8.7%) | 3/24 (12.5%) | 1/24 (4.2%) | 4/24 (16.7%) | 4/23 (17.4%) | 6/23 (26.1%) | ||||||
| Nausea | 1/23 (4.3%) | 0/24 (0%) | 1/24 (4.2%) | 0/24 (0%) | 3/23 (13%) | 1/23 (4.3%) | ||||||
| Vomiting | 1/23 (4.3%) | 1/24 (4.2%) | 0/24 (0%) | 1/24 (4.2%) | 2/23 (8.7%) | 0/23 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Nasopharyngitis | 1/23 (4.3%) | 2/24 (8.3%) | 0/24 (0%) | 1/24 (4.2%) | 0/23 (0%) | 0/23 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Headache | 4/23 (17.4%) | 0/24 (0%) | 2/24 (8.3%) | 1/24 (4.2%) | 3/23 (13%) | 4/23 (17.4%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT 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.
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:
NCT01811953
Other Study ID Numbers:
- 1276.8
- 2012-005156-42
First Posted:
Mar 15, 2013
Last Update Posted:
Jul 27, 2015
Last Verified:
Jun 1, 2015