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

NCT03562624 | Completed Phase 2

• 2 other identifiers: 177002018-000128-33
• Study Type: interventional
• Target: 177
• Locations: 2 countries
• Sites: 7

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

Outcome Measures

Primary Outcomes (1)

• Number of uterine bleeding/spotting (B/S) days during treatment

  Recorded by participants with electronic diary

  90 days after start of treatment

Secondary Outcomes (2)

• Number of subjects showing endometrial histology typical for intrauterine LNG application in biopsies taken at the end of treatment

  On day 90 after start of treatment

• Frequency of treatment emergent adverse events

  90 days after start of treatment

Study Arms (4)

BAY98-7443 (low IND dose)

EXPERIMENTAL

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

Drug: BAY98-7443

BAY98-7443 (middle IND dose)

EXPERIMENTAL

Combi IUS Treatment, LNG with medium dose of IND

Drug: BAY98-7443

BAY98-7443 (high IND dose)

EXPERIMENTAL

Combi IUS Treatment, LNG with highest dose of IND

Drug: BAY98-7443

Marketed comparator

ACTIVE COMPARATOR

Marketed comparator IUS

Drug: Levonogestrel (Skyla, BAY86-5028)

Interventions

BAY98-7443 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); BAY98-7443 (low IND dose); BAY98-7443 (middle IND dose)

Levonogestrel (Skyla, BAY86-5028) DRUG

Comparative LNG dose

Also known as: Jaydess

Marketed comparator

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bayer: lead

Study Sites (7)

Nuvisan GmbH

Neu-Ulm, Bavaria, 89231, Germany

Location

Frauenarztpraxis Dr. Wetzel

Blankenburg, Saxony-Anhalt, 38889, Germany

Location

Dinox GmbH Berlin

Berlin, 10115, Germany

Location

CRS Clinical Research Services Berlin GmbH

Berlin, 13353, Germany

Location

CTC North GmbH & Co. KG

Hamburg, 20251, Germany

Location

Praxis Hr. Dr. K. Peters

Hamburg, 22159, Germany

Location

PAREXEL International Early Phase Clinical Unit (London)

Harrow, HA1 3UJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36648744 DERIVED

MeSH Terms

Interventions

Levonorgestrel

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: June 19, 2018
• Study Start: June 22, 2018
• Primary Completion: May 16, 2019
• Study Completion: August 1, 2019
• Last Updated: August 12, 2019

Record last verified: 2019-08

Locations

DE (6); GB (1)