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

• Sponsor: Bayer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02490774
• Collaborator: (none)
• Enrollment: 174
• Locations: 7
• Arms: 6
• Actual Duration (Months): 13
• Patients Per Site: 24.9
• Patients Per Site Per Month: 1.9

Study Details

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
• 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: Jun 22, 2015
• Actual Primary Completion Date: May 26, 2016
• Actual Study Completion Date: Jul 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 [Daily recorded during 90 days treatment period]

2. 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.

3. Ovulation(Yes/no) [Treatment period 90 days]

Secondary Outcome Measures

1. 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]

2. Bleeding characterization (Intensity, pattern) [For 90 day treatment period]

   Classified using a 5-step scale from "none" to "heavy"

3. Serum levels of estradiol [Repeatedly under 90 day treatment]

4. Serum levels of progesterone [Repeatedly under 90 day treatment]

5. Serum levels of luteinizing hormone [Repeatedly under 90 day treatment]

6. Serum levels of follicle-stimulating hormone [Repeatedly under 90 day treatment]

7. 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

8. Number of participants with adverse events as a measure of safety and tolerability. [up to 5 months]

9. Cmax of BAY1007626 [treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,]

10. AUC of BAY1007626 [treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95]

11. T1/2 of BAY1007626 [treatment period days 13,20,30,41,55,62,72, 90, 91, 92,93,95]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hannover	Niedersachsen	Germany	30459
2		Berlin		Germany	10115
3		Berlin		Germany	13353
4		Hamburg		Germany	22159
5		Hamburg		Germany	22351
6		Groningen		Netherlands	9713GZ
7		Belfast		United Kingdom	BT2 7BA

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02490774
• Other Study ID Numbers: 15731; 2013-003980-74
• First Posted: Jul 7, 2015
• Last Update Posted: Jun 4, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Levonorgestrel

Study Results

No Results Posted as of Jun 4, 2019