Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the possible effect of multiple oral doses of BI 425809 on the steady state pharmacokinetics of ethinylestradiol (EE) and levonogestrel (LNG) (administered as the combined oral contraceptive Microgynon®).
Interventions
DRUGMicrogynon®
ethinylestradiol (EE) and levonorgestrel (LNG)
DRUGIclepertin
Iclepertin
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Fixed sequence: Run in period-Reference-Treatment
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy premenopausal female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure(BP), Pulse rate (PR)), 12-lead Electrocardiogram (12-lead ECG), and clinical laboratory tests without any clinically significant abnormalities. * Age of 18 to 35 years (inclusive). * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive). * Signed and dated written informed consent in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial. * Female subjects who meet any of the following criteria starting from at least 30 days before the first administration of BI 425809 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).
Exclusion criteria
Subjects will not be allowed to participate, if any of the following general criteria apply: * Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator. * Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre(s) of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm). * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance. * Any evidence of a concomitant disease assessed as clinically relevant by the investigator. * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders. * Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or 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. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Measured Concentration of Ethinylestradiol (EE) in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss ) | From within 10 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the administration of Microgynon® with and without Iclepertin on day 21. | This outcome measured the minimum measured concentration of ethinylestradiol (EE), an active ingredient of Microgynon®, in plasma at steady state over a uniform dosing interval, following the administration of Microgynon® with and without Iclepertin. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model including effects on the sources of variation: treatment. The effect 'subjects within sequences' will be considered as random, whereas the other effects will be considered as fixed. |
| Minimum Measured Concentration of Levonorgestrel (LNG) in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss ) | From within 10 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the administration of Microgynon® with and without Iclepertin on day 21. | This outcome measured the minimum measured concentration of Levonorgestrel (LNG), an active ingredient of Microgynon®, in plasma at steady state over a uniform dosing interval, following the administration of Microgynon® with and without Iclepertin. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model including effects on the sources of variation: treatment. The effect 'subjects within sequences' will be considered as random, whereas the other effects will be considered as fixed. |
| Area Under the Concentration-time Curve of Ethinylestradiol (EE) in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | From within 10 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the administration of Microgynon® with and without Iclepertin on day 21. | This outcome measured the area under the concentration-time curve of ethinylestradiol (EE), an active ingredient of Microgynon®, in plasma at steady state over a uniform dosing interval, following the administration of Microgynon® with and without Iclepertin. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model including effects on the sources of variation: treatment. The effect 'subjects within sequences' will be considered as random, whereas the other effects will be considered as fixed. |
| Area Under the Concentration-time Curve of Levonogestrel (LNG) in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | From within 10 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the administration of Microgynon® with and without Iclepertin on day 21. | This outcome measured the area under the concentration-time curve of levonogestrel (LNG), an active ingredient of Microgynon®, in plasma at steady state over a uniform dosing interval, following the administration of Microgynon® with and without Iclepertin. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model including effects on the sources of variation: treatment. The effect 'subjects within sequences' will be considered as random, whereas the other effects will be considered as fixed. |
| Maximum Measured Concentration of Ethinylestradiol (EE) in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | From within 10 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the administration of Microgynon® with and without Iclepertin on day 21. | This outcome measured the maximum measured concentration of ethinylestradiol (EE), an active ingredient of Microgynon®, in plasma at steady state over a uniform dosing interval, following the administration of Microgynon® with and without Iclepertin. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model including effects on the sources of variation: treatment. The effect 'subjects within sequences' will be considered as random, whereas the other effects will be considered as fixed. |
| Maximum Measured Concentration of Levonorgestrel (LNG) in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | From within 10 minutes before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the administration of Microgynon® with and without Iclepertin on day 21. | This outcome measured the maximum measured concentration of levonorgestrel (LNG), an active ingredient of Microgynon®, in plasma at steady state over a uniform dosing interval, following the administration of Microgynon® with and without Iclepertin. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model including effects on the sources of variation: treatment. The effect 'subjects within sequences' will be considered as random, whereas the other effects will be considered as fixed. |
Countries
Germany
Participant flow
Recruitment details
This was a non-randomised, open-label, 2-period, fixed sequence trial with a run-in period and without a wash-out period between the treatments to test whether Iclepertin (BI 425809) influences the amount of a contraceptive (Microgynon®) in the blood. Participants underwent a run-in period of at least 28 days before the Period 1 of the trial to exclude any possible interactions with preceding oral contraceptive regime (OC) and to minimize the influence of adaptation to a newly administered OC.
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. Participants were not to be allocated to a treatment group if any of the entry criteria were violated. Nineteen participants enrolled in the trial but only 17 were treated according to the clinical trial protocol: one participant was not treated due to an adverse event (AE) prior to the run-in period, and one other participant was treated with OC but did not start Period 1 and 2 due to an AE.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 27.1 Years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 12 / 18 | 13 / 17 | 15 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 17 |
Outcome results
None listed