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

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation
• Intervention / Treatment: Drug: BAY1834845; Drug: BAY1834845; Drug: Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • Prahealthsciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2017
• Primary Completion (Actual): January 22, 2018
• Study Completion (Actual): July 20, 2018

Study Registration Dates

• First Submitted: August 7, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Actual): July 15, 2019
• Last Update Submitted That Met QC Criteria: July 12, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: 18387; 2016-004393-18 (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