Study to Investigate Safety, Tolerability, Pharmacokinetics, and Drug-drug Interaction of Multiple Oral Doses of BAY1830839 in Healthy Male Participants

Study Overview
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Brief Summary
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The aim of this study is to investigate safety, tolerability and pharmacokinetics of increasing repeated oral doses of BAY1830839 in healthy male participants including the investigation of any potential drug-drug interactions of BAY1830839 with midazolam and methotrexate. In addition, the effects of BAY180839 on exploratory pharmacodynamics biomarkers in healthy participants will be investigated.

Official Title
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Multiple Dose Escalation Study in a Randomized, Double-blind, Placebo-controlled Design to Investigate Safety, Tolerability, Pharmacokinetics, Drug-drug Interaction and Exploratory Pharmacodynamics of Multiple Oral Doses of BAY1830839 in Healthy Male Participants

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: BAY1830839
* Drug: Placebo
* Drug: Midazolam
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent. Overtly healthy as determined by medical evaluation including (medical and surgical history, physical examination, laboratory tests, ECG, vital signs). Confirmation of the participant's health insurance coverage prior to the first screening examination/visit. Body Mass Index (BMI): above or equal 18.5 and below or equal 30.0 kg/m² at screening Male Study participants of reproductive potential must agree to utilize two reliable and acceptable methods of contraception simultaneously when sexually active. This applies for the time period between admission to the study site until 12 weeks after the last administration of the study intervention. The following contraceptive methods will be regarded as adequate in the context of this study: condoms (male or female) with or without a spermicidal agent; diaphragm or cervical cap with spermicide; intra-uterine device; hormone-based contraception. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. The informed consent must be signed before any study specific tests or procedures are done. Ability to understand and follow study-related instructions Exclusion Criteria: Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal. Relevant diseases within the last 4 weeks prior to the first study administration of study intervention. Febrile illness within 4 weeks before the first study administration of study intervention. Known hypersensitivity to any study intervention (active substances or excipients of the preparations) to be used in the study. Known severe allergies, significant non-allergic drug reactions, or multiple drug allergies, e.g. allergies to more than 3 allergens, allergies affecting the lower respiratory tract - allergic asthma, allergies requiring therapy with corticosteroids, or urticaria. Use of systemic or topical medicines or substances which oppose the study objectives or which might influence them within 4 weeks before first study drug administration, e.g. an investigational drug; any drug known to induce liver enzymes (e.g. dexamethasone, barbiturates, rifampicin, anticonvulsants, griseofulvin, St. John's Wort [Hypericum perforatum]). History of COVID-19 as patients with a history of severe COVID-19 infection. Incomplete SARS-CoV-2 vaccination

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1830839 arm<br>Period 1: Dose 1, Dose 2, Dose 3, Dose 4, Dose 5 and Dose 6, single dose. Period 2: Dose 1, Dose 2 and Dose 3, once daily over 10 days. Dose 4 and Dose 5, twice daily over 10 days. Dose 6, single dose on Day 1, three times daily (TID) for 9 days (Days 2-10). | Drug: BAY1830839<br>* Tablet, oral.<br>Drug: Midazolam<br>* For all dose steps. Oral. Two single doses. One dose administered during pre-dose in Period 1 and the second dose administered on the last day of treatment with BAY1830839 or placebo in Period 2<br>Drug: Methotrexate<br>* Only for Dose 3 step. Tablet, oral. Two single doses. One dose administered during pre-dose in Period 1 and the second dose administered on the last day of treatment with BAY1830839 or placebo in Period 2.<br>|
| Placebo Comparator: Placebo arm<br>Placebo tablets matching BAY1830839 | Drug: Placebo<br>* Tablet, oral.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of TEAEs | TEAE: treatment-emergent adverse event | 7 days (period 1) | 
| Frequency of TEAEs |  | 18 days (period 2) | 
| Severity of TEAEs |  | 7 days (period 1) | 
| Severity of TEAEs |  | 18 days (period 2) | 
| AUC(0-24)md of BAY1830839 (QD and TID dosing) | QD:once daily administration TID: three times daily administration | Day 1 period 1 | 
| AUC(0-12)md of BAY1830839 (BID dosing only) | BID:twice daily administration | Day 1 period 2 | 
| Cmax,md of BAY1830839 after multiple dosing |  | 18 days (period 2) | 
| Cav of BAY1830839 after multiple dosing |  | 18 days (period 2) | 
| AUC of midazolam in plasma in presence/absence of BAY1830839 | If AUC(tlast-∞) >20% of AUC then AUC(0-tlast) will replace AUC. | Day -1 period 1 | 
| Cmax of midazolam in plasma in presence/absence of BAY1830839 |  | Day -1 period 1 | 
| AUC of methotrexate in plasma in presence/absence of BAY1830839 | If AUC(tlast-∞) >20% of AUC then AUC(0-tlast) will replace AUC. | Day -1 period 1 (Dose group 3 of BAY1830839 only) | 
| Cmax of methotrexate in plasma in presence/absence of BAY1830839 |  | Day -1 period 1 (Dose group 3 of BAY1830839 only) |