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)

Bayer

Status and phase: Completed; Phase 2

Conditions: Contraception

Treatments: Drug: Levonogestrel (Skyla, BAY86-5028); Drug: BAY98-7443

Study type: Interventional

Funder types: Industry

Identifiers

NCT03562624

17700

2018-000128-33 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 177 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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177 participants in 4 patient groups

BAY98-7443 (low IND dose)

Experimental group

Description:

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

Treatment:

Drug: BAY98-7443

BAY98-7443 (middle IND dose)

Experimental group

Description:

Combi IUS Treatment, LNG with medium dose of IND

Treatment:

Drug: BAY98-7443

BAY98-7443 (high IND dose)

Experimental group

Description:

Combi IUS Treatment, LNG with highest dose of IND

Treatment:

Drug: BAY98-7443

Marketed comparator

Active Comparator group

Description:

Marketed comparator IUS

Treatment:

Drug: Levonogestrel (Skyla, BAY86-5028)