This Study Tests in Healthy Korean Women Which Effects BI 409306 and a Birth-control Pill Have on Each Other

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Microgynon® 30; Drug: BI 409306

• Registration Number: NCT03193307
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The primary objective of this trial is to investigate the effect of multiple doses of ethinylestradiol / levonorgestrel (Microgynon®) on single dose pharmacokinetics of BI 409306 and the effect of single dose of BI 409306 on multiple dose pharmacokinetics of ethinylestradiol / levonorgestrel (Microgynon®)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-20
• Study Start: 2017-06-29
• Primary Completion: 2017-12-01
• Study Completion: 2017-12-01
• Status Verified: 2023-08
• Results First Submitted: 2023-08-10
• Results First Submitted QC: 2023-08-10
• Last Update Submitted: 2023-08-10
• Results First Posted: 2024-03-13
• Last Update Posted: 2024-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 16

Inclusion Criteria

• Healthy CYP2C19 PM genotyped premenopausal female subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests.

• Korean ethnicity according to the following criteria

  ;be a current Korean passport or national identification card holder, and have parents and grandparents who were all born in Korea

• Age of 19 to 40 years (incl.)

• Body Mass Index (BMI) of 18.5 to 25.0 kg/m2 (incl.)

• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

• Female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion:

  • Use of adequate contraception, e.g. non-hormonal intrauterine device plus condom
  • Sexually abstinent
  • A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
  • Surgically sterilised (including hysterectomy)

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Exclusion Criteria

• Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minutes (bpm)
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, oncologic or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• Use of drugs within 30 days prior to administration of trial medication that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
• Participation in another trial (including bioequivalence trial) where an investigational drug has been administered within 3 months prior to planned administration of trial medication
• Current smoker or ex-smoker who quit smoking less than 30 days prior to screening
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 20 g per day)
• Drug abuse or positive drug screening
• Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
• Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
• Inability to comply with dietary regimen of trial site
• Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study.
• Any relevant finding of the gynaecological examination
• Thrombotic predisposition according to thrombophilic testing
• Existing or history of arterial thrombotic or embolic processes, conditions which predispose to them e.g. disorders of the clotting processes, valvular heart disease and atrial fibrillation
• Existing or history of confirmed venous thromboembolism, family history of venous thromboembolism, and other known risk factors for venous thromboembolism.
• Relevant varicosis
• Use of hormone-containing intrauterine device, depot injection or contraceptive implants
• Any history of relevant liver diseases (for instance, disturbances of liver function, jaundice or persistent itching during a previous pregnancy, Dubin-Johnson syndrome, Rotor syndrome, or previous or existing liver tumours)
• Any history of migraine with focal neurological symptoms

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Microgynon® 30 +BI 409306 then BI 409306 alone	Microgynon® 30	Run in period: Microgynon alone Treatment period: Microgynon® 30 +BI 409306 then BI 409306 alone
Microgynon® 30 +BI 409306 then BI 409306 alone	BI 409306	Run in period: Microgynon alone Treatment period: Microgynon® 30 +BI 409306 then BI 409306 alone

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of Levonorgestrel in Plasma Over the Time Interval From 0 to 24 Hour at Steady State (AUC0-24,ss)	PK samples were collected 10 min pre-dose and up to 24 h after administration of Microgynon® 30 (Day 17) and up to 24 h after administration of Microgynon® 30 together with BI 409306 (Day 18).	AUC0-24,ss, area under the concentration-time curve of the levonorgestrel in plasma over the time interval from 0 to 24 hour at steady state.; Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.5, 1, 1.5, 2, 4, 8, 14 and 24 hours (h) after single oral administration of 1 tablet Microgynon® 30 (Day 17) and after single administration of 1 tablet Microgynon® 30 together with one tablet of 25 mg BI 409306 (Day 18).
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	PK samples were collected 10 min pre-dose and up to 72 h after administration of BI 409306 together with Microgynon® 30 (Day 18) and up to 72 h after administration of BI 409306 alone (Day 29).	AUC0-tz , area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 to the last quantifiable concentration is presented.; Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 14, 24, 36, 48 and 72 hours (h) after single oral administration of 1 tablet of 25 mg BI 409306 together with 1 tablet of Microgynon® 30 (Day 18) and after single administration of one tablet of 25 mg BI 409306 alone (Day 29).
Maximum Measured Concentration of BI 409306 in Plasma (Cmax)	PK samples were collected 10 min pre-dose and up to 72 h after administration of BI 409306 together with Microgynon® 30 (Day 18) and up to 72 h after administration of BI 409306 alone (Day 29).	Cmax, maximum measured concentration of BI 409306 in plasma is presented. Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 14, 24, 36, 48 and 72 hours (h) after single oral administration of 1 tablet of 25 mg BI 409306 together with 1 tablet of Microgynon® 30 (Day 18) and after single administration of one tablet of 25 mg BI 409306 alone (Day 29).
Area Under the Concentration-time Curve of Ethinylestradiol in Plasma Over the Time Interval From 0 to 24 Hour at Steady State (AUC0-24,ss)	PK samples were collected 10 min pre-dose and up to 24 h after administration of Microgynon® 30 (Day 17) and up to 24 h after administration of Microgynon® 30 together with BI 409306 (Day 18).	AUC0-24,ss, area under the concentration-time curve of the ethinylestradiol in plasma over the time interval from 0 to 24 hour at steady state.; Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.5, 1, 1.5, 2, 4, 8, 14 and 24 hours (h) after single oral administration of 1 tablet Microgynon® 30 (Day 17) and after single administration of 1 tablet Microgynon® 30 together with one tablet of 25 mg BI 409306 (Day 18).
Maximum Measured Concentration of Ethinylestradiol in Plasma at Steady State (Cmax,ss)	PK samples were collected 10 min pre-dose and up to 24 h after administration of Microgynon® 30 (Day 17) and up to 24 h after administration of Microgynon® 30 together with BI 409306 (Day 18).	Cmax,ss, maximum measured concentration of ethinylestradiol in plasma at steady state is presented.; Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.5, 1, 1.5, 2, 4, 8, 14 and 24 hours (h) after single oral administration of 1 tablet Microgynon® 30 (Day 17) and after single administration of 1 tablet Microgynon® 30 together with one tablet of 25 mg BI409306 (Day 18).
Maximum Measured Concentration of Levonorgestrel in Plasma at Steady State (Cmax,ss)	PK samples were collected 10 min pre-dose and up to 24 h after administration of Microgynon® 30 (Day 17) and up to 24 h after administration of Microgynon® 30 together with BI 409306 (Day 18).	Cmax,ss, maximum measured concentration of levonorgestrel in plasma at steady state is presented.; Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.5, 1, 1.5, 2, 4, 8, 14 and 24 hours (h) after single oral administration of 1 tablet Microgynon® 30 (Day 17) and after single administration of 1 tablet Microgynon® 30 together with one tablet of 25 mg BI409306 (Day 18).

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)	PK samples were collected 10 min pre-dose and up to 72h after administration of BI 409306 together with Microgynon® 30 (Day 18) and up to 72 h after administration of BI 409306 alone (Day 29).	AUC0-infinity, area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 extrapolated to infinity is presented.; Geometric Least Squares Mean and adjusted geometric standard error were derived from an Analysis of variance (ANOVA) model which included random effect for 'subject' and fixed effect for 'treatment'.; Pharmacokinetics samples were collected 10 minutes (min) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 14, 24, 36, 48 and 72 hours (h) after single oral administration of 1 tablet of 25 mg BI 409306 together with 1 tablet of Microgynon® 30 (Day 18) and after single administration of 1 tablet of 25 mg BI 409306 alone (Day 29).

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of