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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: BAY1830839; Drug: Midazolam; Drug: Methotrexate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité Research Organisation GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1830839 arm; 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; Tablet, oral.; Drug: Midazolam; 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; Drug: Methotrexate; 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.
Placebo Comparator: Placebo arm; Placebo tablets matching BAY1830839	Drug: Placebo; Tablet, oral.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2019
• Primary Completion (Actual): January 21, 2022
• Study Completion (Actual): May 11, 2022

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: May 27, 2019
• First Posted (Actual): May 29, 2019

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Midazolam; Methotrexate
• Other Study ID Numbers: 19401; 2019-000632-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No