A Study to Evaluate the Pharmacokinetics of Divarasib in Healthy Participants and Participants With Impaired Hepatic Function

Genentech

Status and phase: Enrolling; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Divarasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06734208

GP45713

Details and patient eligibility

About

This is a phase 1, open-label, single-dose, parallel-cohort study to determine the pharmacokinetics (PK) of divarasib in healthy participants and participants with varying degrees of hepatic impairment, as defined by Child-Pugh classification.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

• Males or females of non-childbearing potential
• Within body mass index (BMI) range of 18.0 to 45.0 kg/m2

Participants with Hepatic Impairment

• Considered to have mild, moderate, or severe hepatic impairment by Child-Pugh Score classification and has been clinically stable for at least 1 month prior to Screening
• Chronic (>6 months), stable hepatic insufficiency with features of cirrhosis due to any etiology. Participants must also remain stable throughout the Screening period

Key Exclusion Criteria

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal (GI), neurological, or psychiatric disorder
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator

Participants with Hepatic Impairment

• Have a QTcF >480 msec for males and >490 msec for females at Screening or Check-in. If any parameter is out of range, the ECG may be repeated for confirmation
• Any evidence of progressive liver disease that has worsened or is worsening, as determined by the investigator, within 1 month prior to Screening
• Demonstrated evidence of hepatorenal syndrome
• Ascites requiring paracentesis or other intervention up to 3 days prior to the study
• 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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40 participants in 4 patient groups

Cohort 1

Experimental group

Description:

Participants will receive a single oral dose of Divarasib on Day 1.

Treatment:

Drug: Divarasib

Cohort 2

Experimental group

Description:

Participants will receive a single oral dose of Divarasib on Day 1.

Treatment:

Drug: Divarasib

Cohort 3

Experimental group

Description:

Participants will receive a single oral dose of Divarasib on Day 1.

Treatment:

Drug: Divarasib

Cohort 4

Experimental group

Description:

Participants will receive a single oral dose of Divarasib on Day 1.

Treatment:

Drug: Divarasib