Trial Outcomes & Findings for Drug-drug Interaction of Empagliflozin (BI 10773) and Microgynon (NCT NCT01328184)
NCT ID: NCT01328184
Last Updated: 2014-06-18
Results Overview
Area under the concentration-time curve of ethinylestradiol in plasma at steady state over the uniform dosing interval τ.
COMPLETED
PHASE1
18 participants
Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.
2014-06-18
Participant Flow
Participant milestones
| Measure |
Study Overall
A open label, two-period, fixed sequence trial. Patients received one tablet of Microgynon once daily for 14 days, immediately followed by one tablet of Microgynon once daily plus 25mg empa once daily for 7 days.
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Drug-drug Interaction of Empagliflozin (BI 10773) and Microgynon
Baseline characteristics by cohort
| Measure |
Study Overall
n=18 Participants
A open label, two-period, fixed sequence trial. Patients received one tablet of Microgynon once daily for 14 days, immediately followed by one tablet of Microgynon once daily plus 25mg empa once daily for 7 days.
|
|---|---|
|
Age, Continuous
|
27.2 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Area under the concentration-time curve of ethinylestradiol in plasma at steady state over the uniform dosing interval τ.
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Area Under the Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)
|
907 pg*h/mL
Geometric Coefficient of Variation 24.4
|
932 pg*h/mL
Geometric Coefficient of Variation 22.8
|
PRIMARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Area under the concentration-time curve of levonorgestrel in plasma at steady state over the uniform dosing interval τ.
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Area Under the Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)
|
94.0 ng*h/mL
Geometric Coefficient of Variation 34.4
|
95.9 ng*h/mL
Geometric Coefficient of Variation 36.6
|
PRIMARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Maximum measured concentration of ethinylestradiol in plasma at steady state over the uniform dosing interval τ.
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Maximum Measured Concentration (Cmax,ss)
|
97.6 pg/mL
Geometric Coefficient of Variation 17.6
|
96.8 pg/mL
Geometric Coefficient of Variation 21.8
|
PRIMARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Maximum measured concentration of levonorgestrel in plasma at steady state over the uniform dosing interval τ.
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Maximum Measured Concentration (Cmax,ss)
|
7.98 ng/mL
Geometric Coefficient of Variation 26.1
|
8.44 ng/mL
Geometric Coefficient of Variation 25.8
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Time from last dosing to the maximum measured concentration of ethinylestradiol in plasma at steady state
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Time From Last Dosing to Maximum Measured Concentration (Tmax,ss)
|
1.26 hours(h)
Full Range 39.5 • Interval 1.0 to 3.05
|
1.50 hours(h)
Full Range 34.2 • Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Time from last dosing to the maximum measured concentration of levonorgestrel in plasma at steady state
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Time From Last Dosing to Maximum Measured Concentration (Tmax,ss)
|
1.00 hours(h)
Full Range 28.1 • Interval 0.5 to 1.52
|
1.00 hours(h)
Full Range 25.5 • Interval 0.5 to 1.5
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Apparent clearance of ethinylestradiol in the plasma at steady state after oral administration
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Apparent Clearance at Steady State (CL/Fss)
|
552 mL/min
Geometric Coefficient of Variation 24.4
|
536 mL/min
Geometric Coefficient of Variation 22.8
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Apparent clearance of levonorgestrel in the plasma at steady state after oral administration
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Apparent Clearance at Steady State (CL/Fss)
|
26.6 mL/min
Geometric Coefficient of Variation 34.4
|
26.1 mL/min
Geometric Coefficient of Variation 36.6
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Apparent volume of distribution during the terminal phase at steady state after oral administration
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Apparent Volume of Distribution During the Terminal Phase at Steady State (Vz/Fss)
|
729 L
Geometric Coefficient of Variation 35.1
|
757 L
Geometric Coefficient of Variation 30.3
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Apparent volume of distribution during the terminal phase at steady state after oral administration
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Apparent Volume of Distribution During the Terminal Phase at Steady State (Vz/Fss)
|
84.6 L
Geometric Coefficient of Variation 41.1
|
85.0 L
Geometric Coefficient of Variation 38.8
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Terminal half-life of ethinylestradiol in plasma at steady state
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Terminal Half-life at Steady State (t1/2,ss)
|
15.3 hours(h)
Geometric Coefficient of Variation 28.8
|
16.3 hours(h)
Geometric Coefficient of Variation 21.8
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Terminal half-life of levonorgestrel in plasma at steady state
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Terminal Half-life at Steady State (t1/2,ss)
|
36.7 hours(h)
Geometric Coefficient of Variation 32.4
|
37.6 hours(h)
Geometric Coefficient of Variation 40.7
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Terminal rate constant of ethinylestradiol in plasma at steady state
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Terminal Rate Constant at Steady State (λz,ss)
|
0.0454 1/h
Geometric Coefficient of Variation 28.8
|
0.0425 1/h
Geometric Coefficient of Variation 21.8
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Terminal rate constant of levonorgestrel in plasma at steady state
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Terminal Rate Constant at Steady State (λz,ss)
|
0.0189 1/h
Geometric Coefficient of Variation 32.4
|
0.0184 1/h
Geometric Coefficient of Variation 40.7
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Mean residence time of ethinylestradiol in the body at steady state after oral administration
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Ethinylestradiol: Mean Residence Time at Steady State (MRTpo,ss)
|
18.6 hours(h)
Geometric Coefficient of Variation 28.1
|
19.5 hours(h)
Geometric Coefficient of Variation 20.5
|
SECONDARY outcome
Timeframe: Pre-dose, 30 min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, and 24h after administration of Microgynon on Days 14 and 21. In addition, pre-dose samples were collected on Days 12, 13, 19, and 20.Population: Pharmacokinetic (PK) set: Included all subjects who took at least one dose of study medication, who provided evaluable data for at least one primary PK endpoint without important protocol violations.
Mean residence time of levonorgestrel in the body at steady state after oral administration
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Levonorgestrel: Mean Residence Time at Steady State (MRTpo,ss)
|
48.8 hours(h)
Geometric Coefficient of Variation 33.1
|
49.6 hours(h)
Geometric Coefficient of Variation 41.2
|
SECONDARY outcome
Timeframe: Day 1 to day 17Population: Treated set (TS) included all subjects who took at least one dose of study medication.
Number of participants with clinically relevant abnormalities in physical examination, vital signs and clinical laboratory tests. Relevant findings or worsenings of baseline conditions were reported as adverse events.
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Number of Participants With Clinically Relevant Abnormalities in Physical Examination, Vital Signs, ECG and Clinical Laboratory Tests.
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Within Day 24 to Day 31Population: Treated set (TS) included all subjects who took at least one dose of study medication.
Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory, bad and not assessable.
Outcome measures
| Measure |
Microgynon
n=18 Participants
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 Participants
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Assessment of Tolerability
Good
|
94.4 percentage of participants
|
94.4 percentage of participants
|
|
Assessment of Tolerability
Satisfactory
|
5.6 percentage of participants
|
5.6 percentage of participants
|
|
Assessment of Tolerability
Not satisfactory
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Assessment of Tolerability
Bad
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Assessment of Tolerability
Not assessable
|
0.0 percentage of participants
|
0.0 percentage of participants
|
Adverse Events
Microgynon
Microgynon Plus Empa
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Microgynon
n=18 participants at risk
One tablet of Microgynon once daily for 14 days.
|
Microgynon Plus Empa
n=18 participants at risk
One tablet of Microgynon once daily plus empa 25mg once daily for seven days
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Gastrointestinal disorders
Nausea
|
5.6%
1/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
General disorders
Fatigue
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
General disorders
Thirst
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Infections and infestations
Rhinitis
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Injury, poisoning and procedural complications
Sunburn
|
5.6%
1/18 • day1 to day17
|
0.00%
0/18 • day1 to day17
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
2/18 • day1 to day17
|
0.00%
0/18 • day1 to day17
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
5.6%
1/18 • day1 to day17
|
0.00%
0/18 • day1 to day17
|
|
Nervous system disorders
Dizziness
|
11.1%
2/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Nervous system disorders
Headache
|
16.7%
3/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/18 • day1 to day17
|
11.1%
2/18 • day1 to day17
|
|
Vascular disorders
Haematoma
|
0.00%
0/18 • day1 to day17
|
5.6%
1/18 • day1 to day17
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place