Clinical trial NCT02490774: To Investigate the 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
Official title: Multi-center, Randomized, Comparator-controlled, Single-blind, Parallel-group Study to Investigate the Pharmacodynamics, Pharmacokinetics and Safety of an Intrauterine System Releasing BAY 1007626, as Compared With Mirena and Jaydess, in a Combined Proof-of-concept and Dose-finding Study in Healthy Pre Menopausal Women Treated for 90 Days
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Contraception
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-07-07
Enrollment: 174
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of bleeding and spotting days
timeFrame: Daily recorded during 90 days treatment period
measure: Progestin effects on endometrial histology
timeFrame: 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).
measure: Ovulation(Yes/no)
timeFrame: Treatment period 90 days
Secondary outcomes:
measure: Endometrial thickness
timeFrame: 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
measure: Bleeding characterization (Intensity, pattern)
timeFrame: For 90 day treatment period
measure: Serum levels of estradiol
timeFrame: Repeatedly under 90 day treatment
measure: Serum levels of progesterone
timeFrame: Repeatedly under 90 day treatment
measure: Serum levels of luteinizing hormone
timeFrame: Repeatedly under 90 day treatment
measure: Serum levels of follicle-stimulating hormone
timeFrame: Repeatedly under 90 day treatment
measure: Cervix function (Insler score)
timeFrame: 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
measure: Number of participants with adverse events as a measure of safety and tolerability.
timeFrame: up to 5 months
measure: Cmax of BAY1007626
timeFrame: treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,
measure: AUC of BAY1007626
timeFrame: treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95
measure: T1/2 of BAY1007626
timeFrame: treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95
Other outcomes:
Locations:
city: Hannover
country: Germany
state: Niedersachsen
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Groningen
country: Netherlands
city: Belfast
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: