Healthy
Conditions
Brief summary
This study aims to investigate the effect of multiple doses of BI 1358894 on pharmacokinetics of ethinylestradiol (EE) and drospirenone (DRSP) (Yasmin®)
Interventions
DRUGYasmin®
Ethinylestradiol (EE) and Drospirenone (DRSP)
DRUGBI 1358894
BI 1358894
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy premenopausal female subjects according to the assessment of the investigator, as based on a complete medical history including a physical and gynaecological examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests 2. Age of 18 to 35 years (inclusive) 3. Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive) 4. Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial 5. Female subject who meet any of the following criteria for a highly effective contraception from at least 30 days before the first administration of trial medication until 30 days after trial completion: * Use of an oral hormonal contraception method in combination with a barrier contraception method and willing to stop the hormonal method and to continue using the barrier method plus Yasmin® for the duration of the trial * Use of non-hormonal intrauterine device (IUD) * Sexually abstinent * Female subject who underwent tubal ligation * A vasectomised sexual partner who received medical assessment of the surgical success (documented absence of sperm) and provided that partner is the sole sexual partner of the trial participant
Exclusion criteria
1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator (e.g. pronounced varicosis, thrombophlebitis, and evidence of peripheral circulatory disturbances) 2. 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 50 to 90 beats per minute (bpm) 3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator 5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair) 7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders 8. History of relevant orthostatic hypotension, fainting spells, or blackouts Further
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Concentration-time Curve of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h) |
| Maximum Measured Concentration of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (Cmax,ss) | Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h) |
Secondary
| Measure | Time frame |
|---|---|
| Minimum Measured Concentration of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (Cmin,ss) | Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h) |
Countries
Germany
Participant flow
Recruitment details
This was a non-randomized, open-label, two-period, fixed-sequence trial involving a run-in phase. The study treated 28 healthy female participants with Yasmin® in the run-in period and aimed to compare Yasmin® (reference treatment) with the combination of Yasmin® and BI 1358894 (test treatment).
Pre-assignment details
29 female participants of child-bearing potential who met all inclusion and no exclusion criteria entered the study, 28 were treated with Yasmin® , 1 was not treated, and 1 withdrew. 27 participants completed the run-in period. No female participant received an investigational medicinal treatment in Period 1 (Yasmin® alone) or Period 2 (Yasmin® and BI 1358894). The study was prematurely discontinued as per protocol in the run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Yasmin® (Reference Treatment) Followed by BI 1358894 and Yasmin® (Test Treatment) All female participants were treated with 1 daily tablet of the contraceptive Yasmin® (ethinylestradiol and drospirenone) during the run-in period (Day-56 to Day-8).
The study was discontinued as per protocol in the run-in period, and thus none of the participants received the planned treatments for period 1 (reference treatment (R)) and for period 2 (test treatment (T)).
Period 1: The planned reference treatment was to administer one tablet of Yasmin® daily after a continental breakfast on Days 1-21 of period 1 (not administered).
Period 2: The planned test treatment consisted of one tablet of Yasmin®, one tablet of BI 1358894 25 milligram (mg) and two tablets of BI 1358894 50 mg (for a total dose of BI 1358894 = 125mg) each administered daily after a continental breakfast on Days 1-21 in period 2 (not administered). | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Run-in Period | Not treated | 1 |
| Run-in Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Yasmin® (Reference Treatment) Followed by BI 1358894 and Yasmin® (Test Treatment) |
|---|---|
| Age, Customized | 30 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 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 | 25 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 9 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Area Under the Concentration-time Curve of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)
Time frame: Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h)
Population: The study was prematurely discontinued as per protocol after run-in period. No pharmacokinetic (PK) parameter values were collected. Therefore, the PK parameter analysis set as defined in the protocol was not applicable.
Primary
Maximum Measured Concentration of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (Cmax,ss)
Time frame: Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h)
Population: The study was prematurely discontinued as per protocol after run-in period. No pharmacokinetic (PK) parameter values were collected. Therefore, the PK parameter analysis set as defined in the protocol was not applicable.
Secondary
Minimum Measured Concentration of Ethinylestradiol and Drospirenone in Plasma at Steady State Over the Uniform Dosing Interval τ (Cmin,ss)
Time frame: Planned: pre-dose within 10 minutes before 1st drug administration, and then in period 1 and period 2 post-dose : 480:30, 481:00, 481:30, 482:00, 482:30, 483:00, 483:30, 484:00, 485:00, 486:00, 488:00, 490:00, 492:00, 504:00 hours (h)
Population: The study was prematurely discontinued as per protocol after run-in period. No pharmacokinetic (PK) parameter values were collected. Therefore, the PK parameter analysis set as defined in the protocol was not applicable.