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)

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

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: BAY98-7443; Drug: Levonogestrel (Skyla, BAY86-5028)

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • CRS Clinical Research Services Berlin GmbH
  • Berlin, Germany, 10115
    • Dinox GmbH Berlin
  • Hamburg, Germany, 20251
    • CTC North GmbH & Co. KG
  • Hamburg, Germany, 22159
    • Praxis Hr. Dr. K. Peters
  • Bayern
    • Neu-Ulm, Bayern, Germany, 89231
      • Nuvisan GmBH
  • Sachsen-Anhalt
    • Blankenburg, Sachsen-Anhalt, Germany, 38889
      • Frauenarztpraxis Dr. Wetzel
• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • PAREXEL International Early Phase Clinical Unit (London)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: Jaydess

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of uterine bleeding/spotting (B/S) days during treatment	Recorded by participants with electronic diary	90 days after start of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2018
• Primary Completion (Actual): May 16, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: June 8, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 17700; 2018-000128-33 (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