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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: BAY1830839; Drug: Placebo; Drug: Midazolam; Drug: Methotrexate

• Registration Number: NCT03965728
• Lead Sponsor: Bayer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-27
• Study First Submitted QC: 2019-05-27
• Study First Posted: 2019-05-29
• Study Start: 2019-06-05
• Primary Completion: 2022-01-21
• Study Completion: 2022-05-11
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-05
• Last Update Posted: 2023-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 67

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BAY1830839 arm	BAY1830839	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).
BAY1830839 arm	Methotrexate	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).
Placebo arm	Placebo	Placebo tablets matching BAY1830839
BAY1830839 arm	Midazolam	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).

Primary Outcome Measures

Name	Time	Method
Cmax,md of BAY1830839 after multiple dosing	18 days (period 2)
AUC(0-24)md of BAY1830839 (QD and TID dosing)	Day 1 period 1	QD:once daily administration TID: three times daily administration
AUC(0-12)md of BAY1830839 (BID dosing only)	Day 1 period 2	BID:twice daily administration
Cav of BAY1830839 after multiple dosing	18 days (period 2)
AUC of midazolam in plasma in presence/absence of BAY1830839	Day -1 period 1	If AUC(tlast-∞) \>20% of AUC then AUC(0-tlast) will replace AUC.
Cmax of methotrexate in plasma in presence/absence of BAY1830839	Day -1 period 1 (Dose group 3 of BAY1830839 only)
Frequency of TEAEs	18 days (period 2)
Severity of TEAEs	18 days (period 2)
AUC of methotrexate in plasma in presence/absence of BAY1830839	Day -1 period 1 (Dose group 3 of BAY1830839 only)	If AUC(tlast-∞) \>20% of AUC then AUC(0-tlast) will replace AUC.
Cmax of midazolam in plasma in presence/absence of BAY1830839	Day -1 period 1

Trial Locations

Locations (1)

Charité Research Organisation GmbH; 🇩🇪 Berlin, Germany