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

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

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

Study Overview

• Status: Terminated
• Conditions: Contraception
• Intervention / Treatment: Drug: BAY1007626; Drug: Jaydess; Drug: Mirena

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
  • Berlin, Germany, 10115
  • Hamburg, Germany, 22159
  • Hamburg, Germany, 22351
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30459
• Netherlands
  • Groningen, Netherlands, 9713GZ
• United Kingdom
  • Belfast, United Kingdom, BT2 7BA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of bleeding and spotting days		Daily recorded during 90 days treatment period
Progestin effects on endometrial histology	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.	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).
Ovulation(Yes/no)		Treatment period 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Classified using a 5-step scale from "none" to "heavy"	For 90 day treatment period
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)	The cervix function is classified using the 4-step 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
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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2015
• Primary Completion (Actual): May 26, 2016
• Study Completion (Actual): July 22, 2016

Study Registration Dates

• First Submitted: June 2, 2015
• First Submitted That Met QC Criteria: July 2, 2015
• First Posted (Estimate): July 7, 2015

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 2, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: 15731; 2013-003980-74 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No