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

Официальное название

Phase 1, Open-label, Fixed-sequence Crossover Study to Investigate the Effect of Sevabertinib on the Pharmacokinetics of Metformin in Healthy Participants

Обзор

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.

Вмешательства

• Препарат Metformin
  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)
• Препарат Sevabertinib (BAY 2927088)
  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

Первичные конечные точки

• AUC (Area Under the Curve) of metformin [Срок оценки: 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 [Срок оценки: Relative to metformin administration on Study Day 1 un until Study Day 4]
• Cmax (Maximum Plasma Concentration) of metformin [Срок оценки: Relative to metformin administration on Study Day 1 un until Study Day 4]

Вторичные конечные точки (2)

• Number of participants with treatment-emergent adverse events (TEAEs) [Срок оценки: 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) [Срок оценки: From the start of study intervention until the last follow-up visit, up to 7 days after the last administration of study intervention.]

Критерии участия

Inclusion:

• 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

Exclusion:

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Clinical Pharmacology of Miami - Oncology — Miami

Идентификаторы

NCT: NCT07753252 · 23182

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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