Study to Assess the Effect of a CYP3A Weak Inducer Rufinamide on Quizartinib Pharmacokinetics in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Quizartinib; Drug: Rufinamide

• Registration Number: NCT06740825
• Lead Sponsor: Daiichi Sankyo

Brief Summary

This study will evaluate the effect of CYP3A weak inducer rufinamide on the pharmacokinetics (PK) of Quizartinib in healthy subjects

Detailed Description

This is a clinical pharmacology study with 2 treatment groups (Test treatment group receiving both rufinamide weak CYP3A inducer and quizartinib and Reference treatment group receiving quizartinib only) investigating the effect of rufinamide on the PK of quizartinib in healthy subjects.

Study Timeline

• Study Start: 2024-10-29
• Status Verified: 2024-12
• Primary Completion: 2024-12-09
• Study Completion: 2024-12-09
• 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

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Male and female subjects 18 to 55 years of age (inclusive), with a BMI of 18 kg/m2 to 32 kg/m2 (inclusive) at Screening.
• Has vital signs (measured after subject has been supine for at least 5 minutes) at Screening within the following ranges: heart rate: 50-100 beats per minute (bpm); systolic blood pressure (BP): 90-145 mmHg; diastolic BP: 50-95 mmHg. Out-of-range vital signs may be repeated once.
• Liver function test results (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and total bilirubin [TBbil]) must be equal to or below the upper limit of normal (ULN). Hemoglobin levels must be ≥11.5 g/dL for female subjects and ≥12.5 g/dL for male subjects.
• In females, documented surgical sterilization (i.e., 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 sterile male partner, or agreement to use 1 of the protocol-approved means of contraception from Screening until 7 months after the dose of quizartinib.
• In males, documented surgical sterilization, or sexual abstinence, or agreement to use 1 of the protocol-approved means of contraception from Screening until 4 months after the dose of quizartini

Key

Exclusion Criteria

• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormality) that could interfere with subject's safety, obtaining informed consent, compliance to the study procedures, or the validity of the study results.
• History of a clinically significant illness, in the opinion of the Investigator, within 4 weeks prior to administration of quizartinib.
• History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically significant and/or a QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 milliseconds (ms) at Screening.
• Females who are pregnant or breastfeeding
• Laboratory results (serum chemistry, hematology, and urinalysis) outside the normal range, if considered clinically significant by the investigator. Estimated creatinine clearance (CrCl)<90 mL/min (calculated by using the Cockcroft-Gault Equation) at Screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group A (Test)	Rufinamide	On Day 1 through Day 32, participants will receive an oral dose of 400-mg of rufinamide twice daily (BID). In addition, on Day 12, subjects will receive an oral single dose of 60-mg quizartinib
Treatment Group A (Test)	Quizartinib	On Day 1 through Day 32, participants will receive an oral dose of 400-mg of rufinamide twice daily (BID). In addition, on Day 12, subjects will receive an oral single dose of 60-mg quizartinib
Treatment Group B (Reference)	Quizartinib	On Day 1, participants will receive an oral dose of 60-mg quizartinib

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameter: Cmax	From day of first dose, Day 1, up to Day 33	Cmax is defined as maximum concentration, determined directly from individual concentration-time data
Pharmacokinetic Parameter: AUClast	From day of first dose, Day 1, up to Day 33	AUClast is defined as 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, up to Day 33	AUCinf is defined as area under the concentration-time curve from time-zero extrapolated to infinity

Secondary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Events (TEAEs)	From day of first dose, Day 1 up to the last day of Safety Follow-up, up to approximately 40 days	TEAEs are defined as new AEs that occur after the first dose of study drug

Trial Locations

Locations (1)

WCT; 🇺🇸 San Antonio, Texas, United States