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

NCT03244462 | Completed Phase 1

• 2 other identifiers: 183872016-004393-18
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Inflammation

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (4)

• 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

Study Arms (4)

Oral BAY1834845

EXPERIMENTAL

Study Part A, cross over sequence: 1. single oral dose of BAY1834845 2. single oral dose of BAY1834845 + i.v. BAY1834845 3. single oral dose of BAY1834845 under fed conditions

Drug: BAY1834845

Oral BAY1834845 + i.v. BAY1834845

EXPERIMENTAL

Study Part A, cross over sequence: 1. single oral dose of BAY1834845+ i.v. BAY1834845 2. single oral dose of BAY1834845 3. single oral dose of BAY1834845 under fed conditions

Drug: BAY1834845

Oral Methotrexate

EXPERIMENTAL

Study part B, cross over sequence: 1. single oral dose of methotrexate (MTX) 2. single oral dose of MTX + single oral dose of BAY1834845

Drug: BAY1834845; Drug: Methotrexate

Oral Methotrexate + oral BAY1834845

EXPERIMENTAL

Study part B, cross over sequence: 1. single oral dose of methotrexate (MTX) + single oral dose of BAY1834845 2. single oral dose of MTX

Drug: BAY1834845; Drug: Methotrexate

Interventions

BAY1834845 DRUG

Single oral dose (IR \[immediate release\] tablets)

Oral BAY1834845; Oral BAY1834845 + i.v. BAY1834845; Oral Methotrexate; Oral Methotrexate + oral BAY1834845

Methotrexate DRUG

Single dose of commercially available MTX

Oral Methotrexate; Oral Methotrexate + oral BAY1834845

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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).
• 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)

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

PRAHealthSciences

Groningen, 9728 NZ, Netherlands

Location

Related Publications (1)

• Feldmuller M, Jodl SJ, Ploeger B, Wagenfeld A, Wiesinger H, Zollmann FS, Klein S, Zhang R, Rohde B, Hochel J. Zabedosertib, a novel interleukin-1 receptor-associated kinase-4 inhibitor, shows a favorable pharmacokinetic and safety profile across multiple phase 1 studies. Front Pharmacol. 2025 May 30;16:1521505. doi: 10.3389/fphar.2025.1521505. eCollection 2025.

  PMID: 40520205 DERIVED

Related Links

• Click here to find results for studies related to Bayer products.

MeSH Terms

Conditions

Inflammation

Interventions

zabedosertib; Methotrexate

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: August 9, 2017
• Study Start: August 18, 2017
• Primary Completion: January 22, 2018
• Study Completion: July 20, 2018
• Last Updated: July 15, 2019

Record last verified: 2019-07

Locations

NL (1)