A Study of Quizartinib Pharmacokinetics in Participants With Moderate Hepatic Impairment

NCT ID: NCT04473664

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-22
• Study Completion Date: 2021-07-22

Brief Summary

Quizartinib is a novel oral Class III receptor tyrosine kinase (RTK) inhibitor exhibiting highly potent and selective but reversible inhibition of Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3). Quizartinib is currently being studied alone or in combination with other agents as a treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in adult and pediatric populations.

Detailed Description

The primary objective of this study is to determine the plasma pharmacokinetics (PK) of quizartinib and its pharmacologically active metabolite AC886 after a single oral dose of 30 mg in participants with moderate hepatic impairment (HI) (as defined by National Cancer Institute-Organ Dysfunction Working Group [NCI-ODWG] criteria) compared to the healthy control participants with normal hepatic function.

Conditions

Hepatic Impairment; Moderate Impaired Hepatic Function

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants with Moderate Hepatic Impairment

Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.

Group Type: EXPERIMENTAL

Quizartinib

Intervention Type: DRUG

Single oral dose, 30 mg tablet

Control Participants with Normal Hepatic Function

Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1.

Group Type: EXPERIMENTAL

Quizartinib

Intervention Type: DRUG

Single oral dose, 30 mg tablet

Interventions

Quizartinib

Single oral dose, 30 mg tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female subjects 18 years to 75 years of age (inclusive), with a body mass index (BMI) of 18 kg/m^2 to 36 kg/m^2 (inclusive)
• In females, documented surgical sterilization, postmenopausal status for at least 1 year (follicle stimulating hormone [FSH] > 40 mIU/mL serum at Screening), or agreement to use an approved form of contraception
• In males, documented surgical sterilization, sexual abstinence, or agreement to use an approved form of contraception from Screening until 6 months after the dose of quizartinib
• In males, agreement to avoid sperm donation for 6 months days after the dose of quizartinib
• Participants must agree to refrain from donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to Screening, and platelets from 6 weeks prior to Screening.
• All participants must be willing to refrain from consuming grapefruit/grapefruit juice, Seville oranges, and pomegranates/pomegranate juice 10 days before the dose of the study drug is given on Day 1 until end-of-study.

Exclusion Criteria

• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormality) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures
• Laboratory results (serum chemistry, hematology, and urinalysis) outside the normal range, if considered clinically significant by the investigator Estimated glomerular filtration rate (eGFR) < 90 mL/min at screening.
• Women who are pregnant or breastfeeding
• Use of any drugs or substances known to be inhibitors or inducers of CYP3A4/5 within 28 days from the first dose or 5 half-lives, if known, of the drugs or substances, whichever is greater, prior to quizartinib administration and during the study.
• Receipt of any prescribed or over-the-counter (OTC) systemic, herbal (including St John's wort), or topical medication within 14 days of quizartinib administration, or any expectation of requiring use of such medication while participating in the study is prohibited.
• A positive drugs of abuse screen from a urine ethanol test (unless the drug is medically prescribed by a licensed health care provider) or alcohol breath test at Screening or at Check-in on Day -1 or a participant who will not agree to smoke ≤10 cigarettes or equivalent per day from Screening up to Enrollment, and is unable to be restricted to ≤5 cigarettes per day and for 6 hours post dose during their period of residence in the clinical unit
• Concomitant use of medications known to affect the elimination of serum creatinine (e.g., trimethoprim or cimetidine) and inhibitors of renal tubular secretion (eg, probenecid) within 14 days or 5 half-lives, if known, of the drugs, whichever is greater, prior to quizartinib administration
• Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome.
• Use of drugs with a risk of QT interval prolongation or torsade de pointes within 14 days of Day -1 (or 5 drug half-lives, if 5 drug half-lives are expected to exceed 14 days)
• Consumption of alcohol- and caffeine-containing beverages within 72 hours prior to check-in and during confinement
• Positive serology for hepatitis B surface antigen (HBsAg) and HCV (healthy subjects), hepatitis A virus (HAV) immunoglobulin M, or anti-human immunodeficiency virus (HIV) Type 1 and Type 2 (all participants)
• Current enrollment in or have not yet completed at least 30 days or 5 elimination half-lives, whichever is longer, since receiving an investigational device or product, or receipt of other investigational agents within 30 days of quizartinib

• Any clinically relevant abnormality identified on the physical examination, ECG, vital signs, or laboratory tests at Screening
• Liver function (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase of liver origin, gamma-glutamyl transferase, and total bilirubin) test results above the upper limit of normal at Screening and during Enrollment on Day -2 are exclusionary. If transaminase levels are >2 × upper limit of normal (ULN) at Screening the participant will be excluded and cannot be rescreened

• Participants with active stage 3 or stage 4 encephalopathy
• Fluctuating or rapidly deteriorating hepatic function as indicated by recent history or worsening of clinical and/or laboratory signs of HI as judged by the investigator
• Participants with severe ascites and/or need of regular paracentesis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Clinical Pharmacology of Miami, LLC

Miami, Florida, United States

Advanced Pharma

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AC220-A-U105

Identifier Type: -

Identifier Source: org_study_id