A Study to Compare 3 Doses of a Hormonal Intra-uterine Device Containing Levonorgestrel and Indomethacin With a Hormonal Intra-uterine Device Containing Only Levonorgestrel to Assess the Effect and Safety of the Combined Components

NCT ID: NCT03562624

Last Updated: 2019-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-22
• Study Completion Date: 2019-08-01

Brief Summary

This study is the first study investigating the combined intrauterine administration of LNG (levonorgestrel) and IND (indomethacin). It is a combined proof-of-concept (PoC) and dose finding (DF) study in pre-menopausal women. It is designed to investigate the pharmacodynamics (PD) of BAY 987443 (i.e. IUS (intrauterine system) releasing LNG and IND), as well as pharmacokinetics (PK) of both active substances, safety and tolerability. In this study, Jaydess, as an LNG-only IUS, will be used as a comparator.

Conditions

Contraception

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

BAY98-7443 (low IND dose)

Combi IUS Treatment, LNG (Levonorgestrel) with lowest dose of IND (indomethacin)

Group Type: EXPERIMENTAL

BAY98-7443

Intervention Type: DRUG

Active ingredient content (in mg IND/LNG):

low dose 6.5 / 13.5; middle dose 12.5 / 13.5; high dose 15.4 / 13.5

BAY98-7443 (middle IND dose)

Combi IUS Treatment, LNG with medium dose of IND

Group Type: EXPERIMENTAL

BAY98-7443

Intervention Type: DRUG

Active ingredient content (in mg IND/LNG):

low dose 6.5 / 13.5; middle dose 12.5 / 13.5; high dose 15.4 / 13.5

BAY98-7443 (high IND dose)

Combi IUS Treatment, LNG with highest dose of IND

Group Type: EXPERIMENTAL

BAY98-7443

Intervention Type: DRUG

Active ingredient content (in mg IND/LNG):

low dose 6.5 / 13.5; middle dose 12.5 / 13.5; high dose 15.4 / 13.5

Marketed comparator

Marketed comparator IUS

Group Type: ACTIVE_COMPARATOR

Levonogestrel (Skyla, BAY86-5028)

Intervention Type: DRUG

Comparative LNG dose

Interventions

BAY98-7443

Active ingredient content (in mg IND/LNG):

low dose 6.5 / 13.5; middle dose 12.5 / 13.5; high dose 15.4 / 13.5

Intervention Type: DRUG

Levonogestrel (Skyla, BAY86-5028)

Comparative LNG dose

Intervention Type: DRUG

Other Intervention Names

Jaydess

Eligibility Criteria

Inclusion Criteria

• Agreement to use an acceptable non-hormonal method of contraception (i.e. male or female condom with or without spermicide; cap, diaphragm or sponge with spermicide) when sexually active. This applies during the pre-treatment cycle and directly following the treatment period until the end of the follow-up period. This is not required if safe contraception is achieved by a permanent method, such as bilateral fallopian tube blockage of the subject or vasectomy of the partner(s).
• Age at screening: 18-45 years inclusive
• Body mass index (BMI) at screening: ≥ 18 and ≤ 32 kg/m²
• No clinically relevant abnormal findings in the pre-treatment endometrial biopsy
• Adequate venous access (for frequent blood sampling)

Exclusion Criteria

• Menstrual disorders with unknown reason (not e.g. oligomenorrhea, hypomenorrhea amenorrhea due to hormonal treatment; not irregularities occurring during menarche). In case it is suspected that the woman is peri-menopausal, she should be excluded.
• Use of short-acting hormonal contraceptives/preparations containing sex hormones (oral, transdermal, intravaginal, IUS) during the pretreatment cycle
• Use of long-acting preparations containing sex hormones within the 40 weeks before the first screening examination (any long-acting injectable or implant)
• History of known or presence of suspected or known malignant tumors, especially any breast cancer, cervical carcinoma in situ or other progestin-sensitive cancer
• History of skin reactions, or other allergic-type reactions or known hypersensitivity reactions after taking aspirin, IND or other NSAIDs or to LNG, or any excipients of the IUSs
• Regular use of corticosteroids, irrespective of route of administration
• Known asthma bronchiale and aspirin-sensitive asthma
• Current or recurrent pelvic inflammatory disease
• Abnormal cervical smear within the last 6 month prior to screening
• Acute genital infection
• Known current thyroid disorders which require treatment (subjects with an euthyroid struma who do not need any treatment can participate)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Nuvisan GmbH

Neu-Ulm, Bavaria, Germany

Frauenarztpraxis Dr. Wetzel

Blankenburg, Saxony-Anhalt, Germany

Dinox GmbH Berlin

Berlin, , Germany

CRS Clinical Research Services Berlin GmbH

Berlin, , Germany

CTC North GmbH & Co. KG

Hamburg, , Germany

Praxis Hr. Dr. K. Peters

Hamburg, , Germany

PAREXEL International Early Phase Clinical Unit (London)

Harrow, , United Kingdom

Countries

Germany; United Kingdom

References

Hofmann BM, Ahola M, Fels LM, Klein S, Lindenthal B, Pihlaja J. Development of an Intrauterine Device Releasing Both Indomethacin and Levonorgestrel During the First Months of Use: Pharmacokinetic Characterization in Healthy Women. Clin Pharmacokinet. 2023 Jan;62(1):113-126. doi: 10.1007/s40262-022-01201-7. Epub 2023 Jan 17.

Reference Type: DERIVED

PMID: 36648744 (View on PubMed)

Other Identifiers

2018-000128-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17700

Identifier Type: -

Identifier Source: org_study_id