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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
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)
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
Clinical Pharmacology of Miami - Oncology
Miami, Florida, United States
AUC (Area Under the Curve) of metformin
Assessed for metformin with and without sevabertinib (Metformin alone vs Metformin + sevabertinib).
Time frame: 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).
Time frame: 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).
Time frame: Relative to metformin administration on Study Day 1 un until Study Day 4
Number of participants with treatment-emergent adverse events (TEAEs)
The number of participants with TEAEs will be summarized by study intervention using Medical Dictionary for Regulatory Activities (MedDRA) terms.
Time frame: 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)
Intensity of AEs should be documented using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.5.0).
Time frame: From the start of study intervention until the last follow-up visit, up to 7 days after the last administration of study intervention.
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