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

A Phase 1, Open Label, Randomized, Parallel Drug Interaction Study to Evaluate the Effect of a CYP3A Weak Inducer Rufinamide on the Pharmacokinetics of Quizartinib in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Quizartinib; Drug: Rufinamide

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • WCT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A (Test); 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	Drug: Quizartinib; Single oral dose of 60 mg; Other Names: VANFLYTA®; Drug: Rufinamide; Twice daily (BID) dose of 400 mg on Days 1 through 32
Experimental: Treatment Group B (Reference); On Day 1, participants will receive an oral dose of 60-mg quizartinib	Drug: Quizartinib; Single oral dose of 60 mg; Other Names: VANFLYTA®

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2024
• Primary Completion (Actual): December 9, 2024
• Study Completion (Actual): December 9, 2024

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Quizartinib
• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Anticonvulsants; Quizartinib; Rufinamide
• Other Study ID Numbers: AC220-164

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No