A Study of Quizartinib Pharmacokinetics in Participants With Moderate Hepatic Impairment

Sponsor
Daiichi Sankyo Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT04473664
Collaborator
(none)
16
3
2
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5.3
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Single-dose Study to Assess the Pharmacokinetics, Safety and Tolerability of Quizartinib in Subjects With Moderate Impaired Hepatic Function as Defined by NCI-ODWG Criteria
Actual Study Start Date :
Sep 29, 2020
Actual Primary Completion Date :
Jul 21, 2021
Actual Study Completion Date :
Jul 21, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Hepatic-impaired Participants

Participants with moderate HI as defined by NCI-ODWG criteria.

Drug: Quizartinib
Single dose of 30 mg quizartinib to be administered orally

Experimental: Healthy Control Participants

Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%).

Drug: Quizartinib
Single dose of 30 mg quizartinib to be administered orally

Outcome Measures

Primary Outcome Measures

  1. Summary of Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Quizartinib and Active Metabolite AC886 [Day 1 through 22 (relative to quizartinib): Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480 and 504 hours post-quizartinib dose]

  2. Summary of Pharmacokinetic Parameter Time to Reach Maximum Serum Concentration (Tmax) for Quizartinib and Active Metabolite AC886 [Day 1 through 22 (relative to quizartinib): Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480 and 504 hours post-quizartinib dose]

  3. Summary of Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Quizartinib and Active Metabolite AC886 [Day 1 through 22 (relative to quizartinib): Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480 and 504 hours post-quizartinib dose]

    Area under the serum concentration-time curve from 0 to the last quantifiable concentration (AUClast) and area under the serum concentration-time curve from 0 extrapolated to infinity (AUCinf) will be assessed.

  4. Summary of Pharmacokinetic Parameter Clearance (CL/F) for Quizartinib and Active Metabolite AC886 [Day 1 through 22 (relative to quizartinib): Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480 and 504 hours post-quizartinib dose]

  5. Summary of Pharmacokinetic Parameter Apparent Volume of Distribution (Vz/F) for Quizartinib and Active Metabolite AC886 [Day 1 through 22 (relative to quizartinib): Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480 and 504 hours post-quizartinib dose]

  6. Summary of Pharmacokinetic Parameter Observed Terminal Half-life (T1/2) for Quizartinib and Active Metabolite AC886 [Day 1 through 22 (relative to quizartinib): Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480 and 504 hours post-quizartinib dose]

Secondary Outcome Measures

  1. Percentage of Participants With Treatment-emergent Adverse Events Following Treatment with Quizartinib [Baseline up to 30 days after last dose, up to approximately 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Male and female subjects 18 years to 75 years of age (inclusive), with a body mass index (BMI) of 18 kg/m2 to 36 kg/m2 (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

Additional Exclusion Criteria for Matched Healthy Participants:
  • 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

Additional Exclusion Criteria for Participants with Hepatic Impairment:
  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Clinical Pharmacology of Miami, LLC Miami Florida United States 33014-3616
2 Advanced Pharma Miami Florida United States 33147
3 Orlando Clinical Research Center Orlando Florida United States 32809

Sponsors and Collaborators

  • Daiichi Sankyo Co., Ltd.

Investigators

  • Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT04473664
Other Study ID Numbers:
  • AC220-A-U105
First Posted:
Jul 16, 2020
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Daiichi Sankyo Co., Ltd.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 18, 2021