A Study to Learn About How BAY2927088 Affects the Level of Midazolam in the Blood When Both Drugs Are Taken Together in Healthy Participants

A Phase 1, Open Label, Fixed Sequence, Crossover Study to Investigate the Effect of BAY 2927088 on the Pharmacokinetics of Midazolam in Healthy Participants

Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC) with specific genetic changes called Epidermal growth factor receptor (EGFR) and Human epidermal growth factor receptor 2 (HER2) mutations.

Advanced NSCLC refers to a type of lung cancer that has spread from the lungs to nearby tissues or other body parts. People with advanced NSCLC may have changes in certain proteins like EGFR and HER2 that cause uncontrolled cell growth and increased spread of cancer.

In this study, participants will be healthy and will not benefit from taking the study treatment, BAY2927088. However, the study will provide information about how to test BAY2927088 in future studies on people with advanced NSCLC with EGFR or HER2 mutations.

BAY2927088 is under development for the treatment of advanced NSCLC with EGFR or HER2 mutations. It is expected to work against these changed proteins, which might slow down the spread of cancer.

Researchers think that BAY2927088 might affect an enzyme (called CYP3A4) that breaks down drugs in the body. This might make the effects of some drugs weaker or stronger. Midazolam is a drug that is broken down by CYP3A4. By studying the level of midazolam in the blood, researchers can understand how BAY2927088 might influence this enzyme's activity.

The main purpose of this study is to find out how BAY2927088, taken as a single dose and as multiple doses, affects the level of another drug, called midazolam, in the blood of healthy participants. To achieve this goal, researchers will measure the following for midazolam when participants take it with or without BAY2927088:

• Area under the curve (AUC): a measure of the total amount of midazolam in participants' blood over time
• Maximum observed concentration (Cmax): the highest amount of midazolam in participants' blood

The study will have 3 treatment periods:

Period 1 (Day 1 to Day 2): On Day 1, participants will take midazolam Period 2 (Day 3 to Day 4): On Day 3, participants will take midazolam with BAY2927088 Period 3 (Day 5 to Day 15): On Days 5 to 13, participants will take BAY2927088 On Day 14, participants will take midazolam with BAY2927088

Participants will be part of the study for about 8 weeks with at least 3 visits to the study clinic.

Participants will visit the study clinic:

• More than/at least once, within 2 to 28 days before the treatment starts
• Once on the day before the treatment starts and will stay in the clinic until Day 15 of the treatment
• Once, within 7 to 10 days after they finish treatment for a health checkup

During the study, the doctors and their study team will:

• do physical examinations
• collect blood samples from the participants to measure the blood levels of midazolam and of BAY2927088
• check participants' health by performing tests such as blood and urine tests, and checking heart health using an electrocardiogram (ECG)
• ask the participants questions about how they are feeling and what adverse events they are having

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Advanced Non-small Cell Lung Cancer; EGFR Mutation; HER2 Mutation
• Intervention / Treatment: Drug: Midazolam; Drug: BAY2927088

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel Baltimore - Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.
• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Participants who are overtly healthy as determined by the investigator or medically qualified designee based on medical evaluation including medical history, laboratory tests, physical, and cardiac examination.
• Participant is a nonsmoker who has not used tobacco- or nicotine- containing products (eg., nicotine patch) for at least 6 months before administration of the first study intervention.
• Body mass index (BMI) within the range 18.0 to 30 kg/m^2 (inclusive) at screening, with bodyweight above/equal to 50 kg.
• Female, of non childbearing potential only. Females must not be pregnant or breastfeeding, and must be documented as a woman of nonchildbearing potential. A negative pregnancy test is required.
• Male study participants of reproductive potential must agree to use adequate contraception when sexually active from signing of the ICF until at least 3 months after the last dose of study intervention, and refrain from sperm donation during study intervention and for 3 months after the last dose of study intervention.
• Participant must be willing to comply with dietary and fluid requirements during the study period (including abstaining from alcohol use).

Exclusion Criteria:

• Existing relevant diseases of vital organs (e.g., liver diseases, heart diseases, gastrointestinal diseases, interstitial lung disease, renal diseases), central nervous system (for example seizures) or other organs (e.g., diabetes mellitus).
• Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination, and effects of the study intervention will not be normal.
• Febrile illness within 4 weeks prior to admission to the clinic.
• Any relevant diseases within 4 weeks prior to the first study intervention administration as judged by the investigator.
• A medical history of risk factors for Torsades de pointes (e.g., family history of long QT syndrome) or other clinically significant arrhythmias as judged by the investigator.
• Known severe allergies, allergies requiring therapy with corticosteroids, significant non-allergic drug reactions, or (multiple) drug allergies (excluding seasonal allergies such as non-severe hay fever that are asymptomatic and untreated during the time of study conduct).
• Known history of hypersensitivity (or known allergic reaction) to BAY 2927088-related compounds, or any components of the formulation, or midazolam.
• History of known or suspected malignant tumors.
• Participants with any type of ongoing psychiatric disorder, especially any mood disorders including medical history with suicidal ideation and/or suicide attempts, which may disable the participant to consent.
• Loss or donation (incl. plasmapheresis) of more than 100 mL of whole blood within 4 weeks or 500 mL of whole blood within 3 months before the first study intervention administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy participants from United States; The healthy volunteers will be confined to the clinic throughout the intervention period of the study. The study includes visits during screening, intervention, and follow-up.	Drug: Midazolam; Oral administration; Drug: BAY2927088; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of midazolam when given with and without BAY2927088	Cmax: Maximum observed drug concentration	From pre-dose up to 24 hours post-dose on Day 1 (Period 1), Day 3 (Period 2) and Day 14 (Period 3)
AUC of midazolam when given with and without BAY2927088	AUC: Area under the concentration vs time curve from zero to infinity	From pre-dose up to 24 hours post-dose on Day 1 (Period 1), Day 3 (Period 2) and Day 14 (Period 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of TEAEs		After the first administration of study intervention up to 7 days after the last administration of study intervention.
Number of participants with TEAEs	TEAEs: treatment-emergent adverse events	After the first administration of study intervention up to 7 days after the last administration of study intervention.

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Actual): June 28, 2024
• Study Completion (Actual): June 28, 2024

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; HER2; EGFR
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 22251 (Other Identifier: City of Hope Medical Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later 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.vivli.org 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 member section of the portal.

Drug and device information, study documents

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