Phase 1 Study in Healthy Adults to See How Sevabertinib Changes Metformin Levels in the Body

NCT07753252 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 23182
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1 study in healthy adults looks at whether sevabertinib changes how the body handles metformin. The study is based on the idea that sevabertinib may block kidney transporters (proteins that move medicines) called MATE1 and MATE2-K, which help remove metformin from the body. Each participant receives a single dose of metformin alone, and later receives sevabertinib for several days and then takes metformin again while still taking sevabertinib. The study aims to learn how metformin, gets into, moves through, and out of the body when it is administered with sevabertinib. This is called "Pharmacokinetics". Furthermore, the study will help us learn about the safety and tolerability of sevabertinib and metformin when given alone or in combination.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (3)

• AUC (Area Under the Curve) of metformin

  Assessed for metformin with and without sevabertinib (Metformin alone vs Metformin + sevabertinib).

  Relative to metformin administration on Study Day 1 un until Study Day 4

• AUC(0-tlast) (Area Under the Curve from time 0 to tlast) of metformin

  Assessed for metformin with and without sevabertinib (Metformin alone vs Metformin + sevabertinib).

  Relative to metformin administration on Study Day 1 un until Study Day 4

• Cmax (Maximum Plasma Concentration) of metformin

  Assessed for metformin with and without sevabertinib (Metformin alone vs Metformin + sevabertinib).

  Relative to metformin administration on Study Day 1 un until Study Day 4

Secondary Outcomes (2)

• Number of participants with treatment-emergent adverse events (TEAEs)

  From the start of study intervention until the last follow-up visit, up to 7 days after the last administration of study intervention.

• Severity of treatment-emergent adverse events (TEAEs)

  From the start of study intervention until the last follow-up visit, up to 7 days after the last administration of study intervention.

Study Arms (1)

Metformin + Sevabertinib

EXPERIMENTAL

Single 500 mg oral dose of metformin on Day 1 (Intervention Period 1) in healthy participants. Sevabertinib pre-treatment period (days -4 to -1) when sevabertinib is administered alone. Single 500 mg oral dose of metformin co-administered during ongoing sevabertinib 20 mg BID regimen on Day 1 of Intervention Period 2; sevabertinib continued on Day 2

Drug: Metformin; Drug: Sevabertinib (BAY 2927088)

Interventions

Metformin DRUG

Immediate-release tablet, 500 mg; administered as a single 500 mg oral dose in Intervention Period 1 (Day 1) and as a single 500 mg oral dose in Intervention Period 2 (Day 1 of the combination phase, after sevabertinib pre-treatment)

Metformin + Sevabertinib

Sevabertinib (BAY 2927088) DRUG

Film-coated tablet, 10 mg; administered as 20 mg BID (oral) pre-treatment in Intervention Period 2 and continued 20 mg BID during co-administration with metformin

Metformin + Sevabertinib

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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, physical examination, 12-lead ECG, and clinical laboratory tests.
• Participant is a non-smoker who has not used tobacco- or nicotine-containing products for at least 6 months before the first study intervention administration.
• Body mass index (BMI) within the range 18.5 to 30.0 kg/m² (inclusive) and a body weight of at least 50 kg at screening.
• Female, of non-childbearing potential only (see Section 10.4.1). Females must not be pregnant or breastfeeding, and must be documented as of non-childbearing potential (WONCBP). A negative pregnancy test is required

You may not qualify if:

• Existing relevant diseases of vital organs (e.g., cardiovascular, liver, gastrointestinal, renal, respiratory, or central nervous system diseases) or other organs (e.g., diabetes mellitus).
• Known history of hypersensitivity to sevabertinib, metformin, or any of their excipients.
• History of known or suspected malignant tumors.
• Regular use of medicines within 4 weeks prior to screening.
• Administration of strong or moderate inhibitors or inducers of CYP3A4, P-gp, MATE1/2-K, or OCT2 within 4 weeks or 5 half-lives prior to the first study intervention administration, whichever is longer.
• Use of any prescription drug or over-the-counter (OTC) medication within 2 weeks or 5 half-lives of the prescription medication prior to the first study intervention administration (whichever is longer), except for occasional use of acetaminophen (up to 2 g/day) within 7 days prior to the first study intervention administration.
• Use of supplements or herbal remedies within 2 weeks prior to the first study intervention administration, except for vitamins.
• Excessive intake of methylxanthine-containing drinks or food (e.g., coffee, tea, chocolate) as judged by the investigator. Excessive intake of methylxanthine is defined as the regular consumption of more than 600 mg of caffeine per day (e.g., \>5 cups of coffee) or would likely be unable to refrain from the use of methylxanthine-containing beverages and food during confinement at the clinic.
• Clinically relevant findings in the ECG such as a second- or third-degree atrio-ventricular block, prolongation of the average QRS complex over 120 msec or of the QTc (Fridericia correction) interval over 450 msec or any other finding which in the opinion of the investigator will hinder participant's safety at screening or check-in (Day-1).
• Positive results for hepatitis B virus surface antigen, hepatitis B virus core antibody, hepatitis C virus antibodies, human immunodeficiency virus antibodies 1 and/or 2 at screening.
• Estimated creatinine clearance \<90 mL/min according to Cockcroft-Gault formula (at screening).
• Positive urine drug and cotinine screening at screening or check-in (Day-1).
• Positive urine alcohol test at screening or check-in (Day-1).
• Unable/unwilling to comply with study restrictions.

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Clinical Pharmacology of Miami - Oncology

Miami, Florida, 33172, United States

Location

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Therapeutic Area Head

CONTACT

4930300139003; clinical-trials-contact@bayer.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: This is a Phase 1, single-center, open-label, non-randomized, fixed sequence, crossover study in healthy participants using an intra-individual comparison (metformin alone vs. metformin with sevabertinib)

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 7, 2026
• Study Start: August 21, 2026
• Primary Completion: September 21, 2026
• Study Completion: September 28, 2026
• Last Updated: August 7, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)