Food Effect, Oral & Intravenous Pharmacokinetics and Absolute Bioavailability of BAY1834845 Including Drug-drug Interaction With Methotrexate

Study Overview
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Brief Summary
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This study is planned to explore the effect of food on the oral pharmacokinetics, the intravenous pharmacokinetics and the absolute bioavailability of BAY1834845. Furthermore, this study will investigate the effect of BAY1834845 on the pharmacokinetics of orally administered methotrexate in healthy male subjects.

Official Title
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Open Label, Randomized, Cross-over Study to Explore the Pharmacokinetics of BAY1834845 After Oral and Intravenous Dosing, Including Food Effect and Absolute Bioavailability (Part A), and to Investigate the Effect of BAY1834845 on the Pharmacokinetics of Orally Administered Methotrexate (Part B) in Healthy Male Subjects

Conditions
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Inflammation

Intervention / Treatment
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* Drug: BAY1834845
* Drug: BAY1834845
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male; healthy according to complete medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory tests as listed in the exclusion criteria given below. Age 18-50 years (inclusive) at the first screening visit. Body mass index: >=18 kg/m² and <=30 kg/m². Sexually active men must agree to practice adequate methods of contraception (protection). This applies for the time period between signing of the informed consent form and up to 90 days after the last administration of the study drug(s). Exclusion Criteria: Any contraindications for intake of BAY 1834845 or methotrexate, gastrointestinal, liver, renal, lung or cardiovascular disorders, malignant tumors, known severe allergies, known or suspected immunodeficiency Medication history: drugs known to induce/inhibit liver enzymes Smoking Clinically relevant findings in physical ECG, blood pressure laboratory values Known hypersensitivity to study drug(s)

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral BAY1834845<br>Study Part A, cross over sequence: single oral dose of BAY1834845 single oral dose of BAY1834845 + i.v. BAY1834845 single oral dose of BAY1834845 under fed conditions | Drug: BAY1834845<br>* Single oral dose (IR [immediate release] tablets)<br>Drug: BAY1834845<br>* I.v. infusion of [13C6]-labeled BAY1834845<br>|
| Experimental: Oral BAY1834845 + i.v. BAY1834845<br>Study Part A, cross over sequence: single oral dose of BAY1834845+ i.v. BAY1834845 single oral dose of BAY1834845 single oral dose of BAY1834845 under fed conditions | Drug: BAY1834845<br>* Single oral dose (IR [immediate release] tablets)<br>Drug: BAY1834845<br>* I.v. infusion of [13C6]-labeled BAY1834845<br>|
| Experimental: Oral Methotrexate<br>Study part B, cross over sequence: single oral dose of methotrexate (MTX) single oral dose of MTX + single oral dose of BAY1834845 | Drug: BAY1834845<br>* Single oral dose (IR [immediate release] tablets)<br>Drug: Methotrexate<br>* Single dose of commercially available MTX<br>|
| Experimental: Oral Methotrexate + oral BAY1834845<br>Study part B, cross over sequence: single oral dose of methotrexate (MTX) + single oral dose of BAY1834845 single oral dose of MTX | Drug: BAY1834845<br>* Single oral dose (IR [immediate release] tablets)<br>Drug: Methotrexate<br>* Single dose of commercially available MTX<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (Area under the concentration-versus-time curve from zero to infinity after single (first) dose) of BAY1834845 after oral administration of BAY1834845 to subjects in fed/fasted state | in study part A | Multiple timepoints up to day 7 | 
| Maximum concentration attained (Cmax) of BAY1834845 after oral administration of BAY1834845 to subjects in fed/fasted state | in study part A | Multiple timepoints up to day 7 | 
| Total body clearance (CL) of [13C6] BAY1834845 after intravenous administration | in study part A | Multiple timepoints up to day 7 | 
| Volume of distribution at steady state (Vss) of [13C6] BAY1834845 after intravenous administration | in study part A | Multiple timepoints up to day 7 | 
| Absolute oral bioavailability (F) of BAY1834845 in the fasted state | in study part A | Multiple timepoints up to day 7 | 
| AUC of methotrexate in plasma in presence/absence of BAY1834845 | in study part B | Multiple timepoints up to day 2 | 
| Cmax of methotrexate in plasma in presence/absence of BAY1834845 | in study part B | Multiple timepoints up to day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Treatment Emergent Adverse Events (TEAEs) in part A |  | Up to 9 weeks | 
| Severity of TEAEs in part A |  | Up to 9 weeks | 
| Frequency of TEAEs in part B |  | Up to 6 weeks | 
| Severity of TEAEs in part B |  | Up to 6 weeks |