Drug-drug Interaction of Empagliflozin (BI 10773) and Microgynon

Study Overview
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Brief Summary
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The objective of this study is to investigate the possible effect of multiple oral doses of 25 mg BI 10773 on the steady state pharmacokinetics of ethinylestradiol (EE) and levonogestrel (LNG) (Microgynon®).

Official Title
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An Open-label, Two-period, Fixed-sequence Trial to Evaluate the Effect of Multiple Doses of BI 10773 on the Multiple-dose Pharmacokinetics of a Combination of Ethinylestradiol and Levonorgestrel in Healthy Premenopausal Female Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: levonorgestrel
* Drug: levonorgestrel
* Drug: Ethinylestradiol
* Drug: Microgynon + BI 10773
* Drug: Ethinylestradiol


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. Healthy female subjects Exclusion criteria: 1. Any relevant deviation from healthy conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reference<br>multiple doses of Microgynon | Drug: levonorgestrel<br>* multiple doses<br>Drug: Ethinylestradiol<br>* multiple doses<br>|
| Active Comparator: Test<br>multiple doses of Microgynon + BI 10773 | Drug: levonorgestrel<br>* multiple doses<br>Drug: Ethinylestradiol<br>* multiple doses<br>Drug: Microgynon + BI 10773<br>* multiple doses BI 10773<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ethinylestradiol: Area Under the Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | Area under the concentration-time curve of ethinylestradiol in plasma at steady state over the uniform dosing interval τ. | 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. | 
| Levonorgestrel: Area Under the Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | Area under the concentration-time curve of levonorgestrel in plasma at steady state over the uniform dosing interval τ. | 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. | 
| Ethinylestradiol: Maximum Measured Concentration (Cmax,ss) | Maximum measured concentration of ethinylestradiol in plasma at steady state over the uniform dosing interval τ. | 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. | 
| Levonorgestrel: Maximum Measured Concentration (Cmax,ss) | Maximum measured concentration of levonorgestrel in plasma at steady state over the uniform dosing interval τ. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ethinylestradiol: Time From Last Dosing to Maximum Measured Concentration (Tmax,ss) | Time from last dosing to the maximum measured concentration of ethinylestradiol in plasma at steady state | 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. | 
| Levonorgestrel: Time From Last Dosing to Maximum Measured Concentration (Tmax,ss) | Time from last dosing to the maximum measured concentration of levonorgestrel in plasma at steady state | 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. | 
| Ethinylestradiol: Apparent Clearance at Steady State (CL/Fss) | Apparent clearance of ethinylestradiol in the plasma at steady state after oral administration | 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. | 
| Levonorgestrel: Apparent Clearance at Steady State (CL/Fss) | Apparent clearance of levonorgestrel in the plasma at steady state after oral administration | 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. | 
| Ethinylestradiol: Apparent Volume of Distribution During the Terminal Phase at Steady State (Vz/Fss) | Apparent volume of distribution during the terminal phase at steady state after oral administration | 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. | 
| Levonorgestrel: Apparent Volume of Distribution During the Terminal Phase at Steady State (Vz/Fss) | Apparent volume of distribution during the terminal phase at steady state after oral administration | 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. | 
| Ethinylestradiol: Terminal Half-life at Steady State (t1/2,ss) | Terminal half-life of ethinylestradiol in plasma at steady state | 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. | 
| Levonorgestrel: Terminal Half-life at Steady State (t1/2,ss) | Terminal half-life of levonorgestrel in plasma at steady state | 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. | 
| Ethinylestradiol: Terminal Rate Constant at Steady State (λz,ss) | Terminal rate constant of ethinylestradiol in plasma at steady state | 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. | 
| Levonorgestrel: Terminal Rate Constant at Steady State (λz,ss) | Terminal rate constant of levonorgestrel in plasma at steady state | 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. | 
| Ethinylestradiol: Mean Residence Time at Steady State (MRTpo,ss) | Mean residence time of ethinylestradiol in the body at steady state after oral administration | 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. | 
| Levonorgestrel: Mean Residence Time at Steady State (MRTpo,ss) | Mean residence time of levonorgestrel in the body at steady state after oral administration | 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. | 
| Number of Participants With Clinically Relevant Abnormalities in Physical Examination, Vital Signs, ECG and Clinical Laboratory Tests. | 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. | Day 1 to day 17 | 
| Assessment of Tolerability | Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory, bad and not assessable. | Within Day 24 to Day 31 |