A Study to Evaluate the Effect of Moderate or Severe Hepatic Impairment on the Pharmacokinetics (PK) of Inavolisib

Официальное название

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Effect of Moderate or Severe Hepatic Impairment on the Pharmacokinetics of Inavolisib

Обзор

This open-label study will evaluate the effect on the pharmacokinetics (PK), safety, and tolerability of a single oral dose of inavolisib in participants with moderate or severe hepatic impairment compared with demographically matched healthy participants with normal hepatic function.

Вмешательства

• Препарат Inavolisib
  Participants will receive a single oral dose of inavolisib

Первичные конечные точки

• Maximum Observed Concentration (Cmax) of Inavolisib [Срок оценки: Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose]
• Area Under Curve (AUC) from Hour 0 to the Last Measurable Concentration (AUC [0-t]) of Inavolisib [Срок оценки: Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose]
• AUC from Zero to Infinity (AUC [0-inf]) Extrapolated of Inavolisib [Срок оценки: Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose]
• Geometric Mean Ratio of Cmax of Inavolisib [Срок оценки: Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose]
• Geometric Mean Ratio of AUC (0-t) of Inavolisib [Срок оценки: Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose]
• Geometric Mean Ratio of AUC (0-inf) of Inavolisib [Срок оценки: Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose]

Вторичные конечные точки (1)

• Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) [Срок оценки: From Baseline up to Follow-up (Day 8)]

Критерии участия

Критерии включения

All participants:

• Body Mass Index 18.0 to 40.0 kilogram per meter square (kg/m\^2), inclusive, and body weight >=45 kg.
• Negative hepatitis B surface antigen (HBsAg) test
• Positive hepatitis B surface antibody (HBsAb) test or negative HBsAb
• Negative HIV (Human Immunodeficiency Virus) test
• Females will not be pregnant or breastfeeding and must be either postmenopausal or surgically sterile
• Males will agree to use contraception and will refrain from sperm donation

Healthy participants (Cohort 1):

• Negative hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV RNA test
• Normal hepatic function and no history of clinically significant hepatic dysfunction

Participants with Hepatic Impairment (Cohorts 2 and 3):

• Considered to have moderate (Child-Pugh score of 7 to 9) or severe (Child-Pugh score of 10 to 15) hepatic impairment
• Chronic, stable hepatic insufficiency with features of cirrhosis
• Negative hepatitis C viral load

Критерии исключения

All participants:

• History of Type 1 diabetes or Type 2 Diabetes that is insulin-dependent or requires ongoing systemic treatment with two or more agents
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder
• Significant illness, surgery, or hospitalization within 2 weeks prior to dosing.
• History of gastro-intestinal surgery
• Malabsorption syndrome or any other condition that would interfere with enteral absorption.
• History of active or latent Mycobacterium tuberculosis (TB), regardless of treatment history, or positive QuantiFERON® TB Gold test
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• Use of drugs of abuse (including opioids)

Healthy participants (Cohort 1):

\- History of alcoholism or drug addiction

Participants with Hepatic Impairment (Cohorts 2 and 3):

• Hepatic impairment due to hepatocellular carcinoma or bile duct cancer
• Surgical or artificial portosystemic shunt (e.g., transjugular intrahepatic portosystemic shunt)
• Evidence of hepatorenal syndrome
• Ascites requiring paracentesis
• Any evidence of progressive liver disease in the last 1 month
• Receipt of a liver transplant
• Hepatic encephalopathy Grade 2 or above

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

Лечение

Центры проведения

США · 4 центра

• Orange County Research Center — Lake Forest
• Orlando Clinical Research Center — Orlando
• The Texas Liver Institute, Inc. — San Antonio
• Pinnacle Clinical Research - San Antonio — San Antonio

Идентификаторы

NCT: NCT07144111 · GP45942

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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