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

Genentech

Status and phase: Enrolling; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Inavolisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT07144111

GP45942

Details and patient eligibility

About

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.

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 3 patient groups

Cohort 1

Experimental group

Description:

Participants with normal hepatic function will receive a single oral dose of inavolisib on Day 1

Treatment:

Drug: Inavolisib

Cohort 2

Experimental group

Description:

Participants with moderate hepatic function will receive a single oral dose of inavolisib on Day 1

Treatment:

Drug: Inavolisib

Cohort 3

Experimental group

Description:

Participants with severe hepatic function will receive a single oral dose of inavolisib on Day 1

Treatment:

Drug: Inavolisib