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Trial record 27 of 187 for:    BI10773

DDI Between BI Empagliflozin (10773) and Verapamil

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ClinicalTrials.gov Identifier: NCT01276301
Recruitment Status : Completed
First Posted : January 13, 2011
Results First Posted : June 17, 2014
Last Update Posted : June 17, 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
Interventions Drug: Verapamil
Drug: BI 10773
Enrollment 16
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Empa / Empa Plus Verapamil Empa Plus Verapamil / Empa
Hide Arm/Group Description A single dose of empagliflozin (empa) 25 mg, followed by a washout period of at least 7 days, followed by a single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil. A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil, followed by a washout period of at least 7 days, followed by a single dose of empagliflozin (empa) 25 mg.
Period Title: First Intervention
Started 8 8
Completed 8 8
Not Completed 0 0
Period Title: Washout Period of 7 Days
Started 8 8
Completed 8 8
Not Completed 0 0
Period Title: Second Intervention
Started 8 8
Completed 8 8
Not Completed 0 0
Arm/Group Title Entire Study Population
Hide Arm/Group Description

An open label, randomised, two-period crossover trial. The two treatments administered were

  • A single dose of empagliflozin (empa) 25 mg
  • A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil

The two treatment periods were separated by a washout period of at least 7 days.

Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
34.3  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
8
  50.0%
Male
8
  50.0%
1.Primary Outcome
Title Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity.
Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
5190
(25.0%)
5340
(25.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa, Empa Plus Verapamil
Comments Ratio calculated as empa plus verapamil divided by empa
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed terms for sequence, period, treatment and random term for subject within sequence.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 102.95
Confidence Interval (2-Sided) 90%
98.87 to 107.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.5
Estimation Comments Standard error of the mean is actually the Intra-Individual geometric coefficient of variation (gCV).
2.Primary Outcome
Title Maximum Measured Concentration (Cmax)
Hide Description Maximum measured concentration of empagliflozin (empa) in plasma.
Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol
785
(31.5%)
725
(29.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa, Empa Plus Verapamil
Comments Ratio calculated as empa plus verapamil divided by empa
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed terms for sequence, period, treatment and random term for subject within sequence.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 92.39
Confidence Interval (2-Sided) 90%
85.38 to 99.97
Parameter Dispersion
Type: Standard Error of the mean
Value: 12.7
Estimation Comments Standard error of the mean is actually the Intra-Individual geometric coefficient of variation (gCV).
3.Secondary Outcome
Title Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
Hide Description Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to time of last quantifiable data point.
Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
5140
(25.0%)
5280
(25.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa, Empa Plus Verapamil
Comments Ratio calculated as empa plus verapamil divided by empa
Type of Statistical Test Non-Inferiority or Equivalence
Comments No formal testing, investigation of relative bioavailability
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed terms for sequence, period, treatment and random term for subject within sequence.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 102.77
Confidence Interval (2-Sided) 90%
98.87 to 106.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.2
Estimation Comments Standard error of the mean is actually the Intra-Individual geometric coefficient of variation (gCV).
4.Secondary Outcome
Title Time From 0 to Maximum Plasma Concentration (Tmax)
Hide Description Time from last dosing to the maximum plasma concentration
Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Median (Full Range)
Unit of Measure: h
1.50
(1.00 to 2.50)
1.75
(0.68 to 3.00)
5.Secondary Outcome
Title Terminal Elimination Rate Constant (λz)
Hide Description

Terminal elimination rate constant in plasma.

Note: The numbers provide below for standard deviation are of Coefficient of Variation.

Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 1/h
0.0573
(29.2%)
0.0531
(30.2%)
6.Secondary Outcome
Title Terminal Half-life in Plasma (t1/2)
Hide Description

Terminal half-life of empagliflozin in plasma.

Note: The numbers provide below for standard deviation are of Coefficient of Variation.

Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
12.1
(29.2%)
13.1
(30.2%)
7.Secondary Outcome
Title Mean Residence Time in the Body After Administration (MRTpo)
Hide Description

Mean residence time of empagliflozin (empa) in the body after oral administration.

Note: The numbers provide below for standard deviation are of Coefficient of Variation.

Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
9.47
(12.0%)
9.95
(13.8%)
8.Secondary Outcome
Title Apparent Clearance in Plasma After Extravascular Administration (CL/F)
Hide Description

Apparent clearance of empagliflozin (empa) in plasma after extravascular administration.

Note: The numbers provide below for standard deviation are of Coefficient of Variation.

Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/min
178
(25.0%)
173
(25.5%)
9.Secondary Outcome
Title Apparent Volume of Distribution Following an Extravascular Dose (Vz/F)
Hide Description

Apparent volume of distribution during the terminal phase following an extravascular dose.

Note: The numbers provide below for standard deviation are of Coefficient of Variation.

Time Frame 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: All subjects who had taken at least one dose of trial medication, who had provided at least one observation for at least one primary PK endpoint without an important protocol violation with respect to the PK evaluation
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
186
(31.8%)
195
(28.8%)
10.Secondary Outcome
Title Clinically Relevant Abnormalities for Physical Examination, Vital Signs, Blood Chemistry and Electrocardiogram (ECG).
Hide Description Clinically relevant abnormalities for physical examination, vital signs , blood chemistry and Electrocardiogram (ECG). New or abnormal findings were reported as adverse events.
Time Frame Day1 to Day 11
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set (TS) included all subjects who had taken at least one dose of trial medication.
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Measure Type: Number
Unit of Measure: participants
0 0
11.Secondary Outcome
Title Assessment of Tolerability by Investigator
Hide Description Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory , bad and not assessable.
Time Frame Within Day 15 to Day 25
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg.
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16 16
Measure Type: Number
Unit of Measure: percentage of participants
Good 100.0 87.5
Satisfactory 0.0 6.3
Not Satisfactory 0.0 6.3
Bad 0.0 0.0
Not assessable 0.0 0.0
12.Other Pre-specified Outcome
Title Verapamil Plasma Concentration
Hide Description

Verapamil plasma concentration were measured in order to confirm exposure.

Note: No descriptive statistics was calculated for predose, 49.0 (h) and 73.0 (h), as most of the values were below the limit of quantification (BLQ).

Time Frame Predose and 1 hour (h), 25h, 49h and 73h after verapamil administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated set (TS) included all subjects who had taken at least one dose of trial medication.
Arm/Group Title Empa Plus Verapamil
Hide Arm/Group Description:
A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
Overall Number of Participants Analyzed 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Planned time: 1.0 (h)
94.5
(76.3%)
Planned time: 25.0(h) (included 11 participants)
2.69
(82.2%)
Time Frame Day1 to Day 11
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empa Empa Plus Verapamil
Hide Arm/Group Description A single dose of empagliflozin (empa) 25 mg. A single dose of empagliflozin (empa) 25 mg one hour after administration of a single dose of 120mg verapamil.
All-Cause Mortality
Empa Empa Plus Verapamil
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empa Empa Plus Verapamil
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/16 (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 Empa Plus Verapamil
Affected / at Risk (%) Affected / at Risk (%)
Total   8/16 (50.00%)   9/16 (56.25%) 
Gastrointestinal disorders     
Constipation  1  0/16 (0.00%)  1/16 (6.25%) 
Diarrhoea  1  0/16 (0.00%)  1/16 (6.25%) 
Nausea  1  0/16 (0.00%)  1/16 (6.25%) 
General disorders     
Induration  1  1/16 (6.25%)  0/16 (0.00%) 
Infections and infestations     
Oral herpes  1  1/16 (6.25%)  2/16 (12.50%) 
Injury, poisoning and procedural complications     
Arthropod bite  1  0/16 (0.00%)  1/16 (6.25%) 
Skeletal injury  1  1/16 (6.25%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/16 (6.25%)  0/16 (0.00%) 
Pain in extremity  1  1/16 (6.25%)  1/16 (6.25%) 
Nervous system disorders     
Dizziness  1  0/16 (0.00%)  1/16 (6.25%) 
Headache  1  3/16 (18.75%)  4/16 (25.00%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  1/16 (6.25%)  0/16 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/16 (6.25%)  0/16 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 13.1
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01276301     History of Changes
Other Study ID Numbers: 1245.43
2010-023059-27 ( EudraCT Number: EudraCT )
First Submitted: January 12, 2011
First Posted: January 13, 2011
Results First Submitted: May 16, 2014
Results First Posted: June 17, 2014
Last Update Posted: June 17, 2014