A Study to Evaluate the Effect of Moderate or Severe Hepatic Impairment on the Pharmacokinetics (PK) of Inavolisib
- Registration Number
- NCT07144111
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 32
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Inavolisib Participants with normal hepatic function will receive a single oral dose of inavolisib on Day 1 Cohort 2 Inavolisib Participants with moderate hepatic function will receive a single oral dose of inavolisib on Day 1 Cohort 3 Inavolisib Participants with severe hepatic function will receive a single oral dose of inavolisib on Day 1
- Primary Outcome Measures
Name Time Method Maximum Observed Concentration (Cmax) of Inavolisib 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 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 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 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 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 Pre-dose (0 hour), 30 minutes (min), 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) From Baseline up to Follow-up (Day 8)