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

• ClinicalTrials.gov Identifier: NCT01328184
• Recruitment Status: Completed
• First Posted: April 4, 2011
• Results First Posted: June 18, 2014
• Last Update Posted: June 18, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

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®).

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: levonorgestrel; Drug: Ethinylestradiol; Drug: Microgynon + BI 10773	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2011
• Actual Primary Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Reference; multiple doses of Microgynon	Drug: levonorgestrel; multiple doses; Drug: Ethinylestradiol; multiple doses
Active Comparator: Test; multiple doses of Microgynon + BI 10773	Drug: levonorgestrel; multiple doses; Drug: Ethinylestradiol; multiple doses; Drug: Microgynon + BI 10773; multiple doses BI 10773

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 39 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

1. Healthy female subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Contacts and Locations

Locations

Germany

1245.41.1 Boehringer Ingelheim Investigational Site

Biberach, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Macha S, Mattheus M, Pinnetti S, Woerle HJ, Broedl UC. Effect of empagliflozin on the steady-state pharmacokinetics of ethinylestradiol and levonorgestrel in healthy female volunteers. Clin Drug Investig. 2013 May;33(5):351-7. doi: 10.1007/s40261-013-0068-y.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01328184
• Other Study ID Numbers: 1245.41; 2010-023432-16 ( EudraCT Number: EudraCT )
• First Posted: April 4, 2011
• Results First Posted: June 18, 2014
• Last Update Posted: June 18, 2014
• Last Verified: May 2014

Additional relevant MeSH terms:

Empagliflozin; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Ethinyl Estradiol-Norgestrel Combination; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Contraceptives, Oral, Hormonal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Contraceptives, Oral, Combined; Contraceptives, Postcoital, Hormonal; Contraceptives, Postcoital; Contraceptives, Postcoital, Synthetic