Assessment of Quizartinib Pharmacokinetic in Subjects With Severe Hepatic Impairment

Phase 1

Recruiting

• Conditions: Hepatic Impairment
• Interventions: Drug: Quizartinib

• Registration Number: NCT06740799
• Lead Sponsor: Daiichi Sankyo

Brief Summary

This study will evaluate and compare the PK in subjects with severe HI to that of matched healthy control subjects with normal hepatic function.

Detailed Description

This is a clinical pharmacology study with 2 cohorts (subjects with severe HI by Child-Pugh criteria and matched healthy control subjects) to evaluate the PK, safety, and tolerability of a single oral dose of 30 mg quizartinib in otherwise healthy subjects with severe HI (as defined by Child-Pugh criteria). This study is planned to be conducted at up to 3 sites in the US, which use Child-Pugh criteria.

Study Timeline

• Study Start: 2024-09-30
• Status Verified: 2024-12
• Study First Submitted: 2024-12-13
• Study First Submitted QC: 2024-12-13
• Last Update Submitted: 2024-12-13
• Study First Posted: 2024-12-18
• Last Update Posted: 2024-12-18
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Voluntarily consents to participate in this study and provides written informed consent before the start of any study-specific procedures.

2. Male and female subjects 18 to 75 years of age (inclusive), with a body mass index (BMI) of 18 kg/m2 to 37 kg/m2 (inclusive) with a minimum body weight of 40 kg at Screening.

3. In females, documented surgical sterilization (ie, documented hysterectomy, bilateral tubal ligation, or bilateral salpingo-oophorectomy, Essure® with hysterosalpingogram [documentation to confirm tubal occlusion 12 weeks after procedure]), postmenopausal status for at least 1 year (follicle stimulating hormone [FSH] > 40 mIU/mL serum and estradiol <40 pg/mL [<147 pmol/L] at Screening), or agreement to have a sterile male partner, or agreement to use 1 of the means of contraception from Screening until 7 months after the dose of quizartinib 4. In females, agreement to not retrieve eggs/ova via assisted reproductive technology (ART) either for their own use or donation while on the study or for 7 months after the last dose of study drug, whichever is later.

4. In males, documented surgical sterilization, sexual abstinence, or agreement to use 1 of the means of contraception from Screening until 4 months after the dose of quizartinib 6. In males, agreement to avoid sperm donation for 4 months after the dose of quizartinib

Key Exclusion:

1. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormality except hepatic impairment) that could interfere with safety, obtaining informed consent, compliance to the study procedures, or the validity of the study results.
2. In the opinion of the investigator, history of a clinically significant illness within 4 weeks prior to administration of quizartinib.
3. Subjects with primary biliary cirrhosis or primary sclerosing cholangitis.
4. Subjects with history of Gilbert's syndrome.
5. Presence or history of clinically severe adverse reaction to any drug or known hypersensitivity to any of the ingredients (including inactive ingredients) of quizartinib.
6. History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (with the exception of appendectomy, hernia repair, and/or cholecystectomy).

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe HI	Quizartinib	Participants will receive a single oral dose of 30 mg quizartinib
Control Group	Quizartinib	Healthy participants will receive a single oral dose of 30 mg quizartinib

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameter: Cmax	From day of first dose, Day 1, through Day 29	Maximum concentration, determined directly from individual concentration-time data
Pharmacokinetic Parameter: Tmax	From day of first dose, Day 1, through Day 29	Time of the maximum concentration
Pharmacokinetic Parameter: AUClast	From day of first dose, Day 1, through Day 29	Area under the concentration-time curve from time-zero to the time of the last quantifiable concentration; calculated using the linear up log down
Pharmacokinetic Parameter: AUCinf	From day of first dose, Day 1, through Day 29	Area under the concentration-time curve from time-zero extrapolated to infinity
Pharmacokinetic Parameter: t1/2	From day of first dose, Day 1, through Day 29	The observed terminal half-life

Secondary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Events	From day of first dose, Day 1, up to 30 days after Day 29	TEAEs are defined as new AEs that occur after the first dose of study drug

Trial Locations

Locations (3)

Clinical Pharmacology of Miami, LLC; 🇺🇸 Miami, Florida, United States

Advanced Pharma; 🇺🇸 Miami, Florida, United States

GCP Research; 🇺🇸 Saint Petersburg, Florida, United States