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Investigation of the Effect of Food on the Bioavailability of a 25 mg Empagliflozin Tablet as Well as Assessment of Dose Proportionality Between 10 mg and 25 mg Empagliflozin Tablets Under Fasting Conditions.

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ClinicalTrials.gov Identifier: NCT01451775
Recruitment Status : Completed
First Posted : October 14, 2011
Results First Posted : June 27, 2014
Last Update Posted : June 27, 2014
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
Enrollment 18
Recruitment Details  
Pre-assignment Details This was a randomised 3 period crossover trial. 18 patients were randomised to one of six treatment sequences and treated. The trial was open label with washout periods of at least 7 days between treatments.
Arm/Group Title Empa 25mg Fasted / Empa 25mg Fed / Empa 10mg Fasted Empa 25mg Fasted / Empa 10mg Fasted / Empa 25mg Fed Empa 25mg Fed / Empa 25mg Fasted / Empa 10mg Fasted Empa 25mg Fed / Empa 10mg Fasted / Empa 25mg Fasted Empa 10mg Fasted / Empa 25mg Fasted / Empa 25mg Fed Empa 10mg Fasted / Empa 25mg Fed / Empa 25mg Fasted
Hide Arm/Group Description

Patients were administered three treatments in the following order:

  • A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
  • A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast
  • A single dose of 10 mg empa after an overnight fast of at least 10 hours.

Patients were administered three treatments in the following order:

  • A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
  • A single dose of 10 mg empa after an overnight fast of at least 10 hours.
  • A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast

Patients were administered three treatments in the following order:

  • A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast
  • A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
  • A single dose of 10 mg empa after an overnight fast of at least 10 hours.

Patients were administered three treatments in the following order:

  • A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast
  • A single dose of 10 mg empa after an overnight fast of at least 10 hours.
  • A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.

Patients were administered three treatments in the following order:

  • A single dose of 10 mg empa after an overnight fast of at least 10 hours.
  • A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
  • A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast

Patients were administered three treatments in the following order:

  • A single dose of 10 mg empa after an overnight fast of at least 10 hours.
  • A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast
  • A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Period Title: Overall Study
Started 3 3 3 3 3 3
Completed 3 3 3 3 3 3
Not Completed 0 0 0 0 0 0
Arm/Group Title Study Overall
Hide Arm/Group Description Total number of patients randomised and treated in the study. This was a randomised 3 period crossover trial. 18 patients were randomised to one of six treatment sequences and treated. The trial was open label with washout periods of at least 7 days between treatments.
Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants
36.1  (7.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
9
  50.0%
Male
9
  50.0%
1.Primary Outcome
Title Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 hours extrapolated to infinity (AUC0-∞).

The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities.
Time Frame 1 hour (h) before study drug and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
All treated subjects who provided at least one observation in the relevant treatment periods for at least one primary pharmacokinetic (PK) endpoint without a relevant protocol deviation and who had not experienced emesis before or at 2 times median tmax in at least one of the two relevant treatment periods.
Arm/Group Title Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Hide Arm/Group Description:
A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.
A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Overall Number of Participants Analyzed 18 17 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
5380
(26.0%)
4520
(24.8%)
2280
(27.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 25 mg Fasted, Empa 25 mg Fed
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability study with standard bioequivalence range of 80% to 125%. Ratio calculated as empa 25mg fed divided by empa 25mg fasted.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 84.04
Confidence Interval (2-Sided) 90%
80.856 to 87.344
Parameter Dispersion
Type: Standard Deviation
Value: 6.4
Estimation Comments Standard deviation is actually the geometric coefficient of variation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 25 mg Fasted, Empa 10 mg Fasted
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments This is an analysis of dose proportionality
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Does proportionality would be assumed if the 95% confidence interval includes one.
Method ANCOVA
Comments ANCOVA with logarithm of the dose fitted as a continuous covariate and sequence, subjects within sequence, period included as categorical variables.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.9367
Confidence Interval (2-Sided) 95%
0.8988 to 0.9746
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.0178
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Measured Concentration (Cmax)
Hide Description

Maximum measured concentration of empagloflozin (empa) in plasma, per period.

The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities.
Time Frame 1 hour (h) before study drug and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
All treated subjects who provided at least one observation in the relevant treatment periods for at least one primary pharmacokinetic (PK) endpoint without a relevant protocol deviation and who had not experienced emesis before or at 2 times median tmax in at least one of the two relevant treatment periods.
Arm/Group Title Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Hide Arm/Group Description:
A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.
A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Overall Number of Participants Analyzed 18 17 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
837
(27.8%)
523
(27.7%)
365
(27.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa 25 mg Fasted, Empa 25 mg Fed
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability study with standard bioequivalence range of 80% to 125%. Ratio calculated as empa 25mg fed divided by empa 25mg fasted.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with terms for sequence, subjects within sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 63.22
Confidence Interval (2-Sided) 90%
56.736 to 70.439
Parameter Dispersion
Type: Standard Deviation
Value: 18.1
Estimation Comments Standard deviation is actually the geometric coefficient of variation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa 25 mg Fasted, Empa 10 mg Fasted
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments This is an analysis of dose proportionality
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Does proportionality would be assumed if the 95% confidence interval includes one.
Method ANCOVA
Comments ANCOVA with logarithm of the dose fitted as a continuous covariate and sequence, subjects within sequence, period included as categorical variables.
Method of Estimation Estimation Parameter Slope
Estimated Value 0.9065
Confidence Interval (2-Sided) 95%
0.8011 to 1.0120
Parameter Dispersion
Type: Standard Deviation
Value: 0.0495
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator.
Hide Description Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry, haematology, urinanalysis and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events (AEs). Time frame for AE reporting includes the period of first drug administration until end of study. A more detailed definition of the used time frame and MedDRA Version can be found in the AE section.
Time Frame Screening until end of trial, average of 45 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set(TS): TS includes all subjects who have taken at least 1 dose of trial medication
Arm/Group Title Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Hide Arm/Group Description:
A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.
A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Overall Number of Participants Analyzed 18 18 18
Measure Type: Number
Unit of Measure: participants
0 0 0
Time Frame Drug administration until beginning of next sequence/end of trial, average of 24 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Hide Arm/Group Description A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours. A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast. A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
All-Cause Mortality
Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/18 (0.00%)   0/18 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Empa 25 mg Fasted Empa 25 mg Fed Empa 10 mg Fasted
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/18 (11.11%)   2/18 (11.11%)   4/18 (22.22%) 
Ear and labyrinth disorders       
Vertigo † 1  0/18 (0.00%)  1/18 (5.56%)  0/18 (0.00%) 
Gastrointestinal disorders       
Abdominal pain † 1  0/18 (0.00%)  1/18 (5.56%)  0/18 (0.00%) 
Nausea † 1  0/18 (0.00%)  1/18 (5.56%)  0/18 (0.00%) 
Vomiting † 1  1/18 (5.56%)  1/18 (5.56%)  0/18 (0.00%) 
Infections and infestations       
Rhinitis † 1  0/18 (0.00%)  0/18 (0.00%)  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders       
Myosclerosis † 1  0/18 (0.00%)  0/18 (0.00%)  1/18 (5.56%) 
Nervous system disorders       
Headache † 1  0/18 (0.00%)  1/18 (5.56%)  2/18 (11.11%) 
Migraine † 1  0/18 (0.00%)  0/18 (0.00%)  1/18 (5.56%) 
Presyncope † 1  0/18 (0.00%)  1/18 (5.56%)  0/18 (0.00%) 
Skin and subcutaneous tissue disorders       
Neurodermatitis † 1  1/18 (5.56%)  0/18 (0.00%)  0/18 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.0
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01451775     History of Changes
Other Study ID Numbers: 1245.79
2011-002836-13 ( EudraCT Number: EudraCT )
First Submitted: October 11, 2011
First Posted: October 14, 2011
Results First Submitted: May 16, 2014
Results First Posted: June 27, 2014
Last Update Posted: June 27, 2014