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

Phase 2

Terminated

• Conditions: Contraception
• Interventions: Drug: BAY1007626; Drug: Jaydess; Drug: Mirena

• Registration Number: NCT02490774
• Lead Sponsor: Bayer

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-02
• Study Start: 2015-06-22
• Study First Submitted QC: 2015-07-02
• Study First Posted: 2015-07-07
• Primary Completion: 2016-05-26
• Study Completion: 2016-07-22
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-02
• Last Update Posted: 2019-06-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 174

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: BAY1007626, low relase	BAY1007626	Intrauterine device with a low in vitro release rate
Arm 2: BAY1007626, low to medium release	BAY1007626	Intrauterine device with a low to medium in vitro release rate
Arm 3: BAY1007626, medium release	BAY1007626	Intrauterine device with a medium in vitro release rate
Arm 4: BAY 1007626, high release	BAY1007626	Intrauterine device with a high in vitro release rate
Arm 5: Levonorgestrel, Jaydess	Jaydess	Intrauterine device releasing levonorgestrel (Jaydess)
Arm 6: Levonorgestrel, Mirena	Mirena	Intrauterine device releasing levonorgestrel (Mirena)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Serum levels of follicle-stimulating hormone	Repeatedly under 90 day treatment
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
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