Contraception
Conditions
Brief summary
Investigation of pharmacological effects, drug blood levels and safety of an intrauterine system releasing the study drug BAY1007626 in comparison to Mirena and Jaydess in healthy young women treated for 90 days to determine the drug dose for further development
Interventions
DRUGBAY1007626
Intrauterine device with 4 different in vitro release rates (low, low to medium, medium, high)
DRUGJaydess
Jaydess: Intrauterine device with a nominal in vitro release of 12 µg levonorgestrel/day
DRUGMirena
Mirena: Intrauterine device with a nominal in vitro release of 20 µg levonorgestrel/day
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy female subject. * Willingness to use non-hormonal methods of contraception during the study. * This applies during the cycle preceding the pre-treatment cycle until the end of follow-up. * Age at screening: 18-40 years inclusive. * Body mass index (BMI) at screening: ≥ 18 and ≤ 32 kg/m². * History of regular cyclic menstrual periods. * No clinically relevant abnormal findings in the pre-treatment endometrial biopsy.
Exclusion criteria
* Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal. * Any presence or history of known or suspected malignant tumors, especially any known or suspected breast cancer or other progestin-sensitive cancer. * Any presence or history of known or suspected benign tumors of the liver or of the pituitary or adrenal gland. * Amenorrhea (with unknown reason, not amenorrhea due to hormonal treatment) for more than 3 months within the 6 months before the first screening examination. * Use of short-acting preparations containing sex hormones during the cycle preceding the pre-treatment cycle (oral, transdermal, intravaginal, IUS). * Use of long-acting preparations containing sex hormones within the 40 weeks before the first screening examination (any long-acting injectable or implant). Clinically relevant findings in the physical examination (e.g. pronounced varicosis, thrombophlebitis, and evidence of peripheral circulatory disturbances). Menstrual disorders with suspicion of ovarian failure (e.g., oligomenorrhea, amenorrhea, hypomenorrhea). * Known bleeding irregularities * Current or recurrent pelvic inflammatory disease, including pelvic inflammatory disease within 6 month prior to the insertion of the IUS and any active sexually transmitted disease. * Anovulatory pre-treatment cycle (ovulation has to be observed by day 27 at the latest). * Positive result of urine pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of bleeding and spotting days | Daily recorded during 90 days treatment period | — |
| Progestin effects on endometrial histology | Data derived from biopsies taken in the pre-treatment cycle, under treatment (between day 42 and day 90 of treatment) and during follow-up (within max. 40 days after IUS removal). | Endometrail histology will be evaluated according to standardized criteria, derived from Blaustein's standard pathology textbook and criteria for secretory-type effects caused by exogenous progestins after intrauterine application. |
| Ovulation(Yes/no) | Treatment period 90 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endometrial thickness | pre-treatment cycle days 6, 9, 12, 15, 18, 21, 24, 27, 30, treatment period days 1, 13, 27, 41, 44, 48, 51, 55, 58, 62, 65, 69, 72, 76, 79, 83, 86, 90 | — |
| Bleeding characterization (Intensity, pattern) | For 90 day treatment period | Classified using a 5-step scale from none to heavy |
| Serum levels of estradiol | Repeatedly under 90 day treatment | — |
| Serum levels of progesterone | Repeatedly under 90 day treatment | — |
| Serum levels of luteinizing hormone | Repeatedly under 90 day treatment | — |
| Serum levels of follicle-stimulating hormone | Repeatedly under 90 day treatment | — |
| Cervix function (Insler score) | cycle day 6,9,12,15,18,23,24,27,40, treatment period days 41,44,48,51,55,58,62,65,69,76,79,80,83,90 | The cervix function is classified using the 4-step Insler Score |
| Number of participants with adverse events as a measure of safety and tolerability. | up to 5 months | — |
| Cmax of BAY1007626 | treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93, | — |
| AUC of BAY1007626 | treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95 | — |
| T1/2 of BAY1007626 | treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95 | — |
Countries
Germany, Netherlands, United Kingdom
Outcome results
None listed