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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01328184
First received: April 1, 2011
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Healthy
Drug: levonorgestrel
Drug: Ethinylestradiol
Drug: Microgynon + BI 10773
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    Area under the concentration-time curve of ethinylestradiol in plasma at steady state over the uniform dosing interval τ.

  • 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. ] [ Designated as safety issue: No ]
    Area under the concentration-time curve of levonorgestrel in plasma at steady state over the uniform dosing interval τ.

  • 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. ] [ Designated as safety issue: No ]
    Maximum measured concentration of ethinylestradiol in plasma at steady state over the uniform dosing interval τ.

  • 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. ] [ Designated as safety issue: No ]
    Maximum measured concentration of levonorgestrel in plasma at steady state over the uniform dosing interval τ.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    Time from last dosing to the maximum measured concentration of ethinylestradiol in plasma at steady state

  • 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. ] [ Designated as safety issue: No ]
    Time from last dosing to the maximum measured concentration of levonorgestrel in plasma at steady state

  • 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. ] [ Designated as safety issue: No ]
    Apparent clearance of ethinylestradiol in the plasma at steady state after oral administration

  • 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. ] [ Designated as safety issue: No ]
    Apparent clearance of levonorgestrel in the plasma at steady state after oral administration

  • 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. ] [ Designated as safety issue: No ]
    Apparent volume of distribution during the terminal phase at steady state after oral administration

  • 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. ] [ Designated as safety issue: No ]
    Apparent volume of distribution during the terminal phase at steady state after oral administration

  • 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. ] [ Designated as safety issue: No ]
    Terminal half-life of ethinylestradiol in plasma at steady state

  • 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. ] [ Designated as safety issue: No ]
    Terminal half-life of levonorgestrel in plasma at steady state

  • 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. ] [ Designated as safety issue: No ]
    Terminal rate constant of ethinylestradiol in plasma at steady state

  • 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. ] [ Designated as safety issue: No ]
    Terminal rate constant of levonorgestrel in plasma at steady state

  • 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. ] [ Designated as safety issue: No ]
    Mean residence time of ethinylestradiol in the body at steady state after oral administration

  • 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. ] [ Designated as safety issue: No ]
    Mean residence time of levonorgestrel in the body at steady state after oral administration

  • Number of Participants With Clinically Relevant Abnormalities in Physical Examination, Vital Signs, ECG and Clinical Laboratory Tests. [ Time Frame: Day 1 to day 17 ] [ Designated as safety issue: No ]
    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.

  • Assessment of Tolerability [ Time Frame: Within Day 24 to Day 31 ] [ Designated as safety issue: No ]
    Tolerability will be assessed by the investigator according to the categories good, satisfactory, not satisfactory, bad and not assessable.


Enrollment: 18
Study Start Date: April 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 39 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01328184

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:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01328184     History of Changes
Other Study ID Numbers: 1245.41, 2010-023432-16
Study First Received: April 1, 2011
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Ethinyl Estradiol
Levonorgestrel
Ethinyl Estradiol-Norgestrel Combination
Ethinyl estradiol, levonorgestrel drug combination
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptives, Oral, Combined
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital

ClinicalTrials.gov processed this record on August 28, 2014