A Phase I Study to Investigate the Pharmacokinetics and Safety of Capivasertib in Participants With Moderate Hepatic Impairment

Официальное название

A Phase I, Single-dose, Non-randomized, Open-label, Parallel Group Study to Assess the Pharmacokinetics and Safety of Capivasertib in Participants With Moderate Hepatic Impairment

Обзор

The purpose of this study is to measure the pharmacokinetics (PK), safety, and tolerability of capivasertib in participants with moderate hepatic impairment and participants with normal hepatic function (as control).

Подробное описание

This is a single dose, non-randomized, open-label, parallel group study. A Screening Period (Day -21 to -2): Participants in moderate impairment group will have an additional assessment of hepatic function stability on Day -7.

Treatment and Residential Period: Participants will be resident at the Investigative Site from Day -1 to Day 4 and will receive a single oral dose of capivasertib on Day 1.

Follow-up Period: Participants will return for a follow-up visit on Days 9 to 11.

Вмешательства

• Препарат Capivasertib
  Capivasertib will be administered orally

Первичные конечные точки

• Area under concentration time curve from zero to infinity (AUCinf) [Срок оценки: From Day 1 to Day 4]
• Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) [Срок оценки: From Day 1 to Day 4]
• Maximum plasma drug concentration (Cmax) [Срок оценки: From Day 1 to Day 4]

Вторичные конечные точки (8)

• Concentration of capivasertib in plasma over time [Срок оценки: From Day 1 to Day 4]
• Area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC0-t) [Срок оценки: From Day 1 to Day 4]
• Time to Cmax (tmax) [Срок оценки: From Day 1 to Day 4]
• Terminal half-life (t½) [Срок оценки: From Day 1 to Day 4]
• Apparent plasma clearance (CL/F) [Срок оценки: From Day 1 to Day 4]
• Renal Clearance (CLR) [Срок оценки: From Day 1 to Day 3]
• Apparent volume of distribution (Vz/F) [Срок оценки: From Day 1 to Day 4]
• Number of participants with Adverse Events (AEs) and Serious AEs [Срок оценки: Up to Day 11]

Критерии участия

Критерии включения

• Body weight of at least 50 kg and Body Mass Index (BMI) of between ≥ 18 up to ≤ 40 kg/m2.
• Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Participants must have suitable veins for cannulation or repeated venipuncture.
• Non-smoker, defined as a participant who has not smoked previously or who has discontinued smoking or the use of other nicotine/nicotine-containing products at least 3 months before the Screening Visit.
• Supporting documents confirming the participant's hepatic impairment must be available (a liver biopsy is preferable but not mandatory); participants must be classified by the Investigator as Child Pugh class B.
• Participants must meet National Cancer Institute - Organ Dysfunction Working Group (NCI-ODWG) classification of total bilirubin 1.5 to 3\*upper limit of normal (ULN) and any Aspartate aminotransferase/transaminase (AST) for moderate hepatic impairment.
• Stable hepatic impairment
• For participants with normal hepatic function, Bilirubin < 1.5 × ULN, alanine aminotransferase (ALT), AST, albumin, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) < 1.2 × ULN. Creatinine < ULN. White blood cell count > lower limit of normal (LLN).

Критерии исключения

• Any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, significant aneurysm, renal transplant and active bleeding diseases) which makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of capivasertib.
• History of primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.
• Active tuberculosis infection.
• Known Human Immunodeficiency Virus (HIV) infection, active hepatitis B or C infection, positive hepatitis C antibody, and/or positive hepatitis B virus surface antigen.
• Clinically significant abnormalities of glucose metabolism as defined by HemoglobinA1c (HbA1c) ≥ 8.0% (63.9 mmol/mol) at screening.
• Moderate or severe renal dysfunction according to age-related creatinine clearance estimated using CKD-EPI formula (i.e., creatinine clearance less than 60 mL/min).
• Fluctuating or rapidly deteriorating hepatic function.
• Presence of a hepatocellular carcinoma or acute liver disease caused by an infection or drug toxicity.
• Severe portal hypertension or surgical porto-systemic shunts.
• Biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
• Clinically relevant hepatic encephalopathy (Grade 3 or more).
• Severe ascites.
• Esophageal variceal bleeding (unless banded) within the past 2 months.
• Post-liver transplantation.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 2 центра

• Research Site — Rialto
• Research Site — San Antonio

Идентификаторы

NCT: NCT07343960 · D3615C00004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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