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

• ClinicalTrials.gov Identifier: NCT02490774
• Recruitment Status: Terminated
• First Posted: July 7, 2015
• Last Update Posted: June 4, 2019
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

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

Condition or disease	Intervention/treatment	Phase
Contraception	Drug: BAY1007626; Drug: Jaydess; Drug: Mirena	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 174 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 22, 2015
• Actual Primary Completion Date: May 26, 2016
• Actual Study Completion Date: July 22, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: BAY1007626, low relase; Intrauterine device with a low in vitro release rate	Drug: BAY1007626; Intrauterine device with 4 different in vitro release rates (low, low to medium, medium, high)
Experimental: Arm 2: BAY1007626, low to medium release; Intrauterine device with a low to medium in vitro release rate	Drug: BAY1007626; Intrauterine device with 4 different in vitro release rates (low, low to medium, medium, high)
Experimental: Arm 3: BAY1007626, medium release; Intrauterine device with a medium in vitro release rate	Drug: BAY1007626; Intrauterine device with 4 different in vitro release rates (low, low to medium, medium, high)
Experimental: Arm 4: BAY 1007626, high release; Intrauterine device with a high in vitro release rate	Drug: BAY1007626; Intrauterine device with 4 different in vitro release rates (low, low to medium, medium, high)
Active Comparator: Arm 5: Levonorgestrel, Jaydess; Intrauterine device releasing levonorgestrel (Jaydess)	Drug: Jaydess; Jaydess: Intrauterine device with a nominal in vitro release of 12 µg levonorgestrel/day
Active Comparator: Arm 6: Levonorgestrel, Mirena; Intrauterine device releasing levonorgestrel (Mirena)	Drug: Mirena; Mirena: Intrauterine device with a nominal in vitro release of 20 µg levonorgestrel/day

Outcome Measures

Primary Outcome Measures :

1. Number of bleeding and spotting days [ Time Frame: Daily recorded during 90 days treatment period ]
2. Progestin effects on endometrial histology [ Time Frame: 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.
3. Ovulation(Yes/no) [ Time Frame: Treatment period 90 days ]

Secondary Outcome Measures :

1. Endometrial thickness [ Time Frame: 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 ]
2. Bleeding characterization (Intensity, pattern) [ Time Frame: For 90 day treatment period ]
   Classified using a 5-step scale from "none" to "heavy"
3. Serum levels of estradiol [ Time Frame: Repeatedly under 90 day treatment ]
4. Serum levels of progesterone [ Time Frame: Repeatedly under 90 day treatment ]
5. Serum levels of luteinizing hormone [ Time Frame: Repeatedly under 90 day treatment ]
6. Serum levels of follicle-stimulating hormone [ Time Frame: Repeatedly under 90 day treatment ]
7. Cervix function (Insler score) [ Time Frame: 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
8. Number of participants with adverse events as a measure of safety and tolerability. [ Time Frame: up to 5 months ]
9. Cmax of BAY1007626 [ Time Frame: treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93, ]
10. AUC of BAY1007626 [ Time Frame: treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95 ]
11. T1/2 of BAY1007626 [ Time Frame: treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

Germany

Hannover, Niedersachsen, Germany, 30459

Berlin, Germany, 10115

Berlin, Germany, 13353

Hamburg, Germany, 22159

Hamburg, Germany, 22351

Netherlands

Groningen, Netherlands, 9713GZ

United Kingdom

Belfast, United Kingdom, BT2 7BA

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02490774
• Other Study ID Numbers: 15731; 2013-003980-74 ( EudraCT Number )
• First Posted: July 7, 2015
• Last Update Posted: June 4, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Levonorgestrel; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral