Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Genentech, Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
What safety data exists for Divarasib or similar treatments?
There is no specific safety data available for Divarasib, but similar treatments like regorafenib, a type of tyrosine kinase inhibitor, have been associated with liver-related side effects. These include increased levels of liver enzymes and bilirubin, which can indicate liver damage, so regular liver function tests are recommended.
12345Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
Eligibility Criteria
This trial is for male or female adults who are not able to bear children, have a BMI between 18.0 and 45.0 kg/m2, and suffer from chronic liver disease that's been stable for at least one month before screening. It excludes those with fluctuating or unstable liver conditions.Inclusion Criteria
I cannot become pregnant or get someone pregnant.
My BMI is between 18.0 and 45.0.
Exclusion Criteria
My heart's electrical cycle is longer than normal, and I have liver issues.
I have had fluid removed from my abdomen within the last 3 days.
I have been diagnosed with hepatorenal syndrome.
I have moderate to severe confusion due to liver problems.
Participant Groups
The study tests how Divarasib, a drug under investigation, behaves in the body (its pharmacokinetics) of healthy individuals compared to those with different levels of liver impairment as classified by the Child-Pugh score.
4Treatment groups
Experimental Treatment
Group I: Cohort 4Experimental Treatment1 Intervention
Participants will receive a single oral dose of Divarasib on Day 1.
Group II: Cohort 3Experimental Treatment1 Intervention
Participants will receive a single oral dose of Divarasib on Day 1.
Group III: Cohort 2Experimental Treatment1 Intervention
Participants will receive a single oral dose of Divarasib on Day 1.
Group IV: Cohort 1Experimental Treatment1 Intervention
Participants will receive a single oral dose of Divarasib on Day 1.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Orlando Clinical Research CenterOrlando, FL
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Who is running the clinical trial?
Genentech, Inc.Lead Sponsor
References
Risk of tyrosine kinase inhibitors-induced hepatotoxicity in cancer patients: a meta-analysis. [2022]Although existing evidence from clinical trials has demonstrated manifestation of hepatic adverse events (AEs) with the use of tyrosine kinase inhibitors (TKIs), overall risks have yet to be reported. Thus we conducted a meta-analysis to determine the risk of hepatotoxicity associated with the use of TKIs, by comparing the occurrence of hepatotoxicity of the TKI arms against that of comparison arms.
Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy. [2021]The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials.
Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis. [2018]Anti-programmed cell death receptor-1 (PD-1) antibodies have demonstrated antitumor activity in many cancer entities. Hepatic adverse events (AEs) are one of its major side effects, but the overall risks have not been systematically evaluated. Thus, we conducted this meta-analysis to investigate the overall incidence and risk of developing hepatic AEs in cancer patients treated with PD-1 inhibitors.
Incidence and risk of regorafenib-induced hepatotoxicity. [2019]Regorafenib, an oral multi-kinase inhibitor, has been approved for the treatments of several malignancies. Unlike traditional cytotoxic chemotherapeutic agents, regorafenib therapy often induces a distinct profile of adverse events (AEs) including hepatotoxicity. Here we conducted an up-to-date meta-analysis to assess the incidence and risk of regorafenib related hepatic toxicities. PubMed and Embase database were reviewed from inception to June 2017 for relevant trials. Eligible studies include subjects with solid tumors treated with 160 mg of regorafenib daily during the first three week of each four-week cycle, and adequate safety data reporting the elevation of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Statistical analyses were conducted to calculate the summary incidence and relative risk (RR). A total of 2,213 subjects from 14 trials were included. The incidences of regorafenib-associated all-grade and high-grade hepatotoxicity were: bilirubin elevation: 23% and 5%; AST elevation: 32% and 6%; ALT elevation: 27% and 5%; ALP elevation: 31% and 2%. Regorafenib-treated subjects had a significant increased risk of all-grade (RR = 3.10; 95% CI, 2.22-4.34) and high-grade (RR = 1.74; 95% CI, 1.09-2.80) bilirubin elevation; all-grade (RR = 1.51; 95% CI, 1.13-2.00) and high-grade (RR = 1.79; 95% CI, 1.00-3.22) AST elevation; all-grade (RR = 1.82; 95% CI, 1.25-2.64) and high-grade (RR = 3.07; 95% CI, 1.30-7.22) ALT elevation; and all-grade (RR = 2.11; 95% CI, 1.01-4.40) ALP elevation. Our results suggest that regorafenib is associated with an increased risk of hepatic toxicities. Hepatotoxicity examination at regular intervals should be advised to clinicians.
Mutational profile of skin lesions in hepatocellular carcinoma patients under tyrosine kinase inhibition: a repercussion of a wide-spectrum activity. [2021]Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib.