A Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on Pharmacokinetics of Sitravatinib

Hepatic Impairment Clinical Trial

Official title:

A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04772612
• Other study ID #: 516-012
• Status: Completed
• Phase: Phase 1
• Start date: March 12, 2021
• Est. completion date: April 13, 2023

Study information

• Verified date: October 2023
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild, Moderate, and Severe Hepatic Impairment on the Single-Dose Pharmacokinetics of Sitravatinib

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 13, 2023
• Est. primary completion date: July 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Males or females, of any race, between 18 and 75 years of age, inclusive, at screening.

• Body mass index between 18.0 and 40.0 kg/m2, inclusive, at screening.

• Females of childbearing potential will not be pregnant or lactating and must have a negative result on an approved pregnancy test at screening and check-in. Females of childbearing potential must agree to use contraception by a method of proven reliability (including abstinence) as detailed in the protocol.

• Male subjects must agree to use contraception as detailed in the protocol.

• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Participants with normal hepatic function must also satisfy the following criteria:

• Participants with normal hepatic function must be in good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, or clinical laboratory evaluations at screening and check-in as assessed by the investigator.

Participants with hepatic impairment must also satisfy the following criteria:

• Participants must meet the criteria for mild, moderate, or severe hepatic impairment based on Child Pugh (CP) score and classification as detailed in the protocol. Hepatically-impaired participants will be assigned to groups according to CP scores calculated at screening; CP scores will be recalculated at check-in to confirm that subjects do not have significant changes in status to ensure subject safety for the study, as determined by the investigator and medical monitor.

Key Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator.

• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications (Cholecystectomy is not allowed.).

• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives prior to dosing, whichever is longer.

• Participants who, in the opinion of the investigator, should not participate in this study.

Participants with normal hepatic function will be excluded from the study if any of the following criteria are applicable:

• Significant history or clinical manifestation of any hepatic disease, as determined by lab abnormalities: AST, ALT, alkaline phosphatase, or alpha-fetoprotein >1 × upper limit of normal or as deemed clinically significant by the investigator.

• Participant has creatinine clearance <80 mL/minute as calculated by using the Cockcroft-Gault equation.

• Use or intend to use any prescription medications/products within 14 days prior to dosing, unless deemed acceptable by the investigator, medical monitor, and sponsor.

Participants with hepatic impairment will be excluded from the study if any of the following criteria are applicable:

• Ventricular dysfunction or history of risk factors for Torsades de Pointes (eg, unexplained syncope, known long QT syndrome, heart failure, and cardiomyopathy).

• Participant has had a change in disease status within 90 days prior to the study drug administration on Day 1, as documented by the subject's medical history, deemed clinically significant by the investigator.

• Participant has required a new medication or a change in medication dose within 2 weeks before dosing with sitravatinib.

• Participant has a current functioning organ transplant or is waiting for an organ transplant.

• History of unstable diabetes mellitus as evidenced by hemoglobin A1c =9% at screening.

• Uncontrolled arterial hypertension (> 150 mm Hg systolic or >100 mm Hg diastolic) on multiple observations despite standard of care treatment.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• sitravatinib
sitravatinib

Locations

Country	Name	City	State
United States	Texas Liver Institute	Austin	Texas
United States	Clinical Pharmacology of Miami	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Nucleus Network	Saint Paul	Minnesota
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics - AUClast (sitravatinib)	AUC from time zero to the last measured time point	9 days
Primary	Pharmacokinetics - Tmax (sitravatinib)	Time to reach maximum observed plasma concentration	9 days
Primary	Pharmacokinetics - AUC8 (sitravatinib)	Area under the plasma concentration-time curve from time zero extrapolated to infinity moderate, or severe hepatic impairment compared to control subjects with normal hepatic function	9 days
Primary	Pharmacokinetics - Cmax (sitravatinib)	Maximum observed plasma concentration	9 days
Primary	Pharmacokinetics - t1/2 (sitravatinib)	Terminal elimination half-life	9 days
Primary	Pharmacokinetics - CL/F (sitravatinib)	Apparent total plasma clearance when dosed orally	9 days
Primary	Pharmacokinetics - Vz/F (sitravatinib)	Apparent volume of distribution when dosed orally	9 days
Primary	Pharmacokinetics - fu (sitravatinib)	Unbound fraction	days 1 - 4
Secondary	Adverse Events (AEs)	Incidence and severity of adverse events (AEs).	From the time the ICF is signed until 14 ± 2 days after the last dose of sitravatinib treatment