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

NCT03965728 | Completed Phase 1

• 2 other identifiers: 194012019-000632-26
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (12)

• 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)

Study Arms (2)

BAY1830839 arm

EXPERIMENTAL

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; Drug: Midazolam; Drug: Methotrexate

Placebo arm

PLACEBO COMPARATOR

Placebo tablets matching BAY1830839

Drug: Placebo

Interventions

BAY1830839 DRUG

Tablet, oral.

BAY1830839 arm

Placebo DRUG

Tablet, oral.

Placebo arm

Midazolam DRUG

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

BAY1830839 arm

Methotrexate DRUG

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.

BAY1830839 arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Charité Research Organisation GmbH

Berlin, 10117, Germany

Location

Related 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.

MeSH Terms

Interventions

Midazolam; Methotrexate

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: May 29, 2019
• Study Start: June 5, 2019
• Primary Completion: January 21, 2022
• Study Completion: May 11, 2022
• Last Updated: May 9, 2023

Record last verified: 2023-05

Locations

DE (1)