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Trial record 29 of 3084 for:    Area Under Curve AND Healthy

Drug-interaction Trial in Healthy Subjects With Oral Administration of Empagliflozin (BI 10773), Rifampicin and Probenecid

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ClinicalTrials.gov Identifier: NCT01634100
Recruitment Status : Completed
First Posted : July 6, 2012
Results First Posted : July 3, 2014
Last Update Posted : July 3, 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: Probenecid
Drug: Rifampicin
Drug: Empagliflozin
Drug: Empagliflozin (BI 10773)
Enrollment 18
Recruitment Details  
Pre-assignment Details This was a randomised, 3-way crossover trial. 18 patients were randomised to one of six treatment sequences and treated. It was an open label trial in which each treatment period lasted 4 days with a washout period of at least 7 days between each.
Arm/Group Title Empa Alone / Empa + Rifampicin / Empa + Probenecid Empa Alone / Empa + Probenecid / Empa + Rifampicin Empa + Rifampicin / Empa Alone / Empa + Probenecid Empa + Rifampicin / Empa + Probenecid / Empa Alone Empa + Probenecid / Empa Alone / Empa + Rifampicin Empa + Probenecid / Empa + Rifampicin / Empa Alone
Hide Arm/Group Description

Patients were administered three treatments in the following order:

  • Empa Alone (A single dose of 10mg of empagliflozin (empa))
  • Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
  • Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)

Patients were administered three treatments in the following order:

  • Empa Alone (A single dose of 10mg of empagliflozin (empa))
  • Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
  • Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)

Patients were administered three treatments in the following order:

  • Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
  • Empa Alone (A single dose of 10mg of empagliflozin (empa))
  • Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)

Patients were administered three treatments in the following order:

  • Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
  • Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
  • Empa Alone (A single dose of 10mg of empagliflozin (empa))

Patients were administered three treatments in the following order:

  • Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
  • Empa Alone (A single dose of 10mg of empagliflozin (empa))
  • Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)

Patients were administered three treatments in the following order:

  • Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
  • Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
  • Empa Alone (A single dose of 10mg of empagliflozin (empa))
Period Title: Overall Study
Started 3 3 3 3 3 3
Received Empa Alone 3 3 3 3 3 3
Received Empa + Rifampicin 3 3 3 3 3 3
Received Empa + Probenecid 2 3 2 3 3 3
Completed 2 3 2 3 3 3
Not Completed 1 0 1 0 0 0
Reason Not Completed
Withdrawal by Subject             1             0             1             0             0             0
Arm/Group Title Study Overall
Hide Arm/Group Description This was a randomised, 3-way crossover trial. 18 patients were randomised to one of six treatment sequences and treated. It was an open label trial in which each treatment period lasted 4 days with a washout period of at least 7 days between each.
Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
Treated Set. Total number of patients randomised and treated in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants
32.7  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
8
  44.4%
Male
10
  55.6%
1.Primary Outcome
Title Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.
Time Frame 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
Arm/Group Title Empa Alone Empa + Rifampicin Empa + Probenecid
Hide Arm/Group Description:
A single dose of 10mg of empagliflozin (empa).
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
Overall Number of Participants Analyzed 18 18 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
2240
(28.1%)
3020
(28.2%)
3400
(28.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa Alone, Empa + Rifampicin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as empa and rifampicin divided by empa
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 135.20
Confidence Interval (2-Sided) 90%
129.58 to 141.06
Parameter Dispersion
Type: Standard Deviation
Value: 7.3
Estimation Comments Standard deviation is actually the intra-subject coefficient of variation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa Alone, Empa + Probenecid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as empa plus probenecid divided by empa
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 153.47
Confidence Interval (2-Sided) 90%
146.41 to 160.88
Parameter Dispersion
Type: Standard Deviation
Value: 7.4
Estimation Comments Standard deviation is actually the intra-subject coefficient of variation.
2.Primary Outcome
Title Total Empa: Maximum Measured Concentration (Cmax)
Hide Description Maximum measured concentration of total empa in plasma, per period.
Time Frame 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
Arm/Group Title Empa Alone Empa + Rifampicin Empa + Probenecid
Hide Arm/Group Description:
A single dose of 10mg of empagliflozin (empa).
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
Overall Number of Participants Analyzed 18 18 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
301
(31.6%)
527
(27.5%)
373
(30.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa Alone, Empa + Rifampicin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as empa and rifampicin divided by empa
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 175.14
Confidence Interval (2-Sided) 90%
160.14 to 191.56
Parameter Dispersion
Type: Standard Deviation
Value: 15.4
Estimation Comments Standard deviation is actually the intra-subject coefficient of variation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa Alone, Empa + Probenecid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as empa plus probenecid divided by empa
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 125.60
Confidence Interval (2-Sided) 90%
113.67 to 138.78
Parameter Dispersion
Type: Standard Deviation
Value: 15.9
Estimation Comments Standard deviation is actually the intra-subject coefficient of variation.
3.Secondary Outcome
Title Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
Hide Description Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to the time of last the quantifiable data point.
Time Frame 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
Arm/Group Title Empa Alone Empa + Rifampicin Empa + Probenecid
Hide Arm/Group Description:
A single dose of 10mg of empagliflozin (empa).
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
Overall Number of Participants Analyzed 18 18 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
2200
(28.6%)
3000
(28.4%)
3350
(29.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Empa Alone, Empa + Rifampicin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as empa and rifampicin divided by empa
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 136.42
Confidence Interval (2-Sided) 90%
130.61 to 142.48
Parameter Dispersion
Type: Standard Deviation
Value: 7.5
Estimation Comments Standard deviation is actually the intra-subject coefficient of variation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Empa Alone, Empa + Probenecid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as empa plus probenecid divided by empa
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment.
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 153.61
Confidence Interval (2-Sided) 90%
146.50 to 161.06
Parameter Dispersion
Type: Standard Deviation
Value: 7.5
Estimation Comments Standard deviation is actually the intra-subject coefficient of variation.
Time Frame Treatment period until end of washout period/end of study examination, up to 29 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Empa Alone Empa + Rifampicin Empa + Probenecid
Hide Arm/Group Description A single dose of 10mg of empagliflozin (empa). A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin. A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
All-Cause Mortality
Empa Alone Empa + Rifampicin Empa + Probenecid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Empa Alone Empa + Rifampicin Empa + Probenecid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/18 (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 Alone Empa + Rifampicin Empa + Probenecid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/18 (38.89%)   9/18 (50.00%)   6/16 (37.50%) 
Gastrointestinal disorders       
Diarrhoea  1  1/18 (5.56%)  0/18 (0.00%)  0/16 (0.00%) 
Nausea  1  2/18 (11.11%)  3/18 (16.67%)  2/16 (12.50%) 
Vomiting  1  2/18 (11.11%)  3/18 (16.67%)  1/16 (6.25%) 
Injury, poisoning and procedural complications       
Muscle strain  1  0/18 (0.00%)  0/18 (0.00%)  1/16 (6.25%) 
Nervous system disorders       
Dizziness  1  0/18 (0.00%)  2/18 (11.11%)  0/16 (0.00%) 
Headache  1  3/18 (16.67%)  5/18 (27.78%)  3/16 (18.75%) 
Presyncope  1  1/18 (5.56%)  0/18 (0.00%)  0/16 (0.00%) 
Sciatica  1  0/18 (0.00%)  1/18 (5.56%)  0/16 (0.00%) 
Vascular disorders       
Haematoma  1  1/18 (5.56%)  0/18 (0.00%)  0/16 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
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: NCT01634100     History of Changes
Other Study ID Numbers: 1245.83
2012-000971-17 ( EudraCT Number: EudraCT )
First Submitted: July 3, 2012
First Posted: July 6, 2012
Results First Submitted: May 16, 2014
Results First Posted: July 3, 2014
Last Update Posted: July 3, 2014