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 (INDessa)

• ClinicalTrials.gov Identifier: NCT03562624
• Recruitment Status: Completed
• First Posted: June 19, 2018
• Last Update Posted: August 12, 2019
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Contraception	Drug: BAY98-7443; Drug: Levonogestrel (Skyla, BAY86-5028)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 177 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 (BAY987443) With Three Different Release Rates of Indomethacin and One Release Rate of Levonorgestrel, as Compared With 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, 2018
• Actual Primary Completion Date: May 16, 2019
• Actual Study Completion Date: August 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: BAY98-7443 (low IND dose); Combi IUS Treatment, LNG (Levonorgestrel) with lowest dose of IND (indomethacin)	Drug: 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
Experimental: BAY98-7443 (middle IND dose); Combi IUS Treatment, LNG with medium dose of IND	Drug: 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
Experimental: BAY98-7443 (high IND dose); Combi IUS Treatment, LNG with highest dose of IND	Drug: 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
Active Comparator: Marketed comparator; Marketed comparator IUS	Drug: Levonogestrel (Skyla, BAY86-5028); Comparative LNG dose; Other Name: Jaydess

Outcome Measures

Primary Outcome Measures :

1. Number of uterine bleeding/spotting (B/S) days during treatment [ Time Frame: 90 days after start of treatment ]
   Recorded by participants with electronic diary

Secondary Outcome Measures :

1. Number of subjects showing endometrial histology typical for intrauterine LNG application in biopsies taken at the end of treatment [ Time Frame: On day 90 after start of treatment ]
2. Frequency of treatment emergent adverse events [ Time Frame: 90 days after start of treatment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

Germany

Nuvisan GmbH

Neu-Ulm, Bayern, Germany, 89231

Frauenarztpraxis Dr. Wetzel

Blankenburg, Sachsen-Anhalt, Germany, 38889

Dinox GmbH Berlin

Berlin, Germany, 10115

CRS Clinical Research Services Berlin GmbH

Berlin, Germany, 13353

CTC North GmbH & Co. KG

Hamburg, Germany, 20251

Praxis Hr. Dr. K. Peters

Hamburg, Germany, 22159

United Kingdom

PAREXEL International Early Phase Clinical Unit (London)

Harrow, United Kingdom, HA1 3UJ

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03562624
• Other Study ID Numbers: 17700; 2018-000128-33 ( EudraCT Number )
• First Posted: June 19, 2018
• Last Update Posted: August 12, 2019
• Last Verified: August 2019

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