Effect of moderate or severe liver impairment on inavolisib pharmacokinetics

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

This trial will test whether a single oral dose of inavolisib behaves differently in people with moderate or severe liver impairment compared with similar healthy people.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Genentech, Inc. (Industry-sponsored)
• Locations: 4 sites (Lake Forest, California and 3 other locations)
• Trial ID: NCT07144111 on ClinicalTrials.gov

What this trial studies

This open-label, single-dose Phase 1 study compares pharmacokinetics, safety, and tolerability of inavolisib in participants with moderate or severe hepatic impairment versus demographically matched participants with normal liver function. Participants with hepatic impairment are enrolled based on Child-Pugh scores (moderate 7–9, severe 10–15) and must have chronic, stable liver insufficiency with cirrhosis features. Healthy control participants have normal hepatic function and are matched by key demographics. Blood sampling for PK analysis and safety monitoring will be performed at site visits following the single oral dose.

Who should consider this trial

Good fit: Ideal candidates are adults with chronic, stable moderate (Child-Pugh 7–9) or severe (Child-Pugh 10–15) hepatic impairment, or matched healthy adults meeting the BMI and lab test criteria and able to attend on-site sampling visits.

Not a fit: People with normal liver function, mild (Child-Pugh A) impairment, pregnant or breastfeeding individuals, or those with uncontrolled viral infections are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, results could help doctors set safe dosing and monitoring recommendations for people with moderate or severe liver impairment taking inavolisib.

How similar studies have performed: Single-dose PK comparisons in hepatic impairment are a well-established approach that has guided dosing for other drugs, though inavolisib-specific hepatic data are currently limited.

Eligibility criteria

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

Where this trial is running

Lake Forest, California and 3 other locations

• Orange County Research Center — Lake Forest, California, United States (Recruiting)
• Orlando Clinical Research Center — Orlando, Florida, United States (Recruiting)
• The Texas Liver Institute, Inc. — San Antonio, Texas, United States (Recruiting)
• Pinnacle Clinical Research - San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Reference Study ID Number: GP45942 https://forpatients.roche.com

Conditions Hepatic Impairment