Quizartinib for Heart Rate Effects

Overseen By Daiichi Sankyo Contact for Clinical Trial Information

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo

Disqualifiers: Pregnancy, Breastfeeding, Abnormal ECG, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how quizartinib, a medication, affects heart rate changes and a specific heart rhythm measurement called QT prolongation (the time it takes for the heart to recharge between beats). Quizartinib is typically used in cancer treatment, but this study focuses on its effects on the heart in healthy individuals. Participants will receive either the medication or a placebo on one day and switch the next day. This trial may suit healthy adults without serious medical conditions and with normal heart and liver function. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to contribute to the foundational knowledge of quizartinib's effects.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that quizartinib is likely to be safe for humans?

Research has shown that quizartinib has been tested in many patients with acute myeloid leukemia (AML). In these studies, serious heart-related side effects, such as the dangerous irregular heartbeat torsades de pointes, were rare, occurring in about 0.2% of patients. Some patients also experienced other heart issues, including cardiac arrest.

Questions remain about how quizartinib affects the heart, especially during sudden changes in heart rate. One study found that higher doses of quizartinib significantly affected heart function, particularly in how the heart resets between beats. This finding suggests that the drug can impact heart rhythms, especially at higher doses.

Overall, while researchers have studied quizartinib for safety, concerns about its effects on heart rate and rhythm persist. These side effects appear rare but are important to consider when deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Quizartinib is unique because it specifically targets and inhibits FLT3, a receptor tyrosine kinase involved in the proliferation of certain cancer cells. Most treatments for conditions involving abnormal heart rates don't focus on this pathway. By targeting FLT3, quizartinib offers a novel approach that could potentially manage heart rate effects in a different way compared to standard options like beta-blockers or calcium channel blockers. Researchers are excited about its potential to provide more tailored and effective treatments with fewer side effects for patients who don't respond well to existing therapies.

What evidence suggests that quizartinib might be an effective treatment for heart rate effects?

Studies have shown that quizartinib effectively treats acute myeloid leukemia (AML), a type of blood cancer. Trials have administered it to over a thousand patients, with serious heart-related side effects, such as the rare fast heartbeat torsades de pointes, occurring in only about 0.2% of patients. Research indicates that quizartinib does not significantly alter heart rate, with an average change of less than 10 beats per minute. However, its safety concerning sudden heart rate changes remains under investigation. In this trial, participants will receive either an oral dose of 90 mg of quizartinib or a placebo on Day 1, with the alternate treatment administered on Day 2. The trial aims to understand how a quick increase in heart rate affects the heart's electrical activity when using quizartinib. ^{2 3 6 7 8}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for healthy individuals who can safely undergo procedures to rapidly increase their heart rate. Specific eligibility details are not provided, but typically participants should have no significant medical conditions.

Inclusion Criteria

I am a male and have been surgically sterilized, practice abstinence, or agree to use contraception.

Vital signs at Screening within specified ranges: heart rate 50-100 bpm, systolic BP 90-145 mmHg, diastolic BP 50-95 mmHg

Liver function test results (ALT, AST, TBil) must be equal to or below the upper limit of normal

Exclusion Criteria

I don't have any serious health or mental conditions that could affect my safety or the study's results.

I haven't had a serious illness in the last 4 weeks.

Pregnant or breastfeeding females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of 90 mg of quizartinib or placebo on Day 1, and the alternate treatment on Day 2

3 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent adverse events

16 days

What Are the Treatments Tested in This Trial?

Interventions

• Quizartinib

Trial Overview The study is testing the effects of a drug called Quizartinib on the electrical activity of the heart when the heart rate is quickly increased. Some people will get Quizartinib and others a placebo (no active ingredient) to compare results.

How Is the Trial Designed?

Group I: Healthy Participants Experimental Treatment 2 Interventions

All participants will receive either an oral dose of 90 mg of quizartinib or placebo on Day 1. On Day 2, all participants will receive the treatment that was not given on Day 1.

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Published Research Related to This Trial

In a study involving 93 healthy subjects, quizartinib showed a significant increase in plasma concentration when coadministered with the strong CYP3A inhibitor ketoconazole, indicating that dose adjustments may be necessary to avoid potential toxicity.

The study found that quizartinib had a low incidence of related adverse events (5.4%), with no serious adverse events or deaths reported, suggesting it is generally safe when administered alone or with moderate CYP3A inhibitors like fluconazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite. Li, J., Kankam, M., Trone, D., et al.[2021]

Quizartinib, a second-generation FLT3 inhibitor, effectively inhibits both mutant and wild-type FLT3 at low concentrations and has shown promising activity and tolerability in phase I and II trials for acute myeloid leukemia, with QT prolongation as a notable side effect.

The drug also inhibits the transport function of ABCG2 and ABCB1 proteins, which may enhance the effectiveness of certain chemotherapy drugs while also raising concerns about potential drug interactions, particularly with medications like ciprofloxacin that can affect heart rhythm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FLT3 inhibitor quizartinib inhibits ABCG2 at pharmacologically relevant concentrations, with implications for both chemosensitization and adverse drug interactions. Bhullar, J., Natarajan, K., Shukla, S., et al.[2021]

Quizartinib, a targeted therapy for acute myeloid leukaemia (AML), shows promise in treating patients with relapsed/refractory FLT3-ITD mutation-positive AML, but careful monitoring of genetic mutations is essential as patients may develop new mutations during treatment.

Patients may experience side effects such as QTc prolongation, which can be managed by dose adjustments, and careful selection of concomitant medications is crucial to avoid drug interactions, especially when preparing for procedures like hematopoietic stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Considerations for Treatment of Relapsed/Refractory FLT3-ITD Acute Myeloid Leukaemia with Quizartinib: Illustrative Case Reports. Martínez-Cuadrón, D., Rodríguez-Macías, G., Rodríguez-Veiga, R., et al.[2020]

In a study involving 64 healthy subjects, quizartinib showed similar absorption profiles whether taken after fasting or with a high-fat meal, indicating it can be administered without food restrictions.

Food intake delayed the time it took for quizartinib to reach its maximum concentration in the blood by 2 hours, but all reported adverse events were mild to moderate, with no serious safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Food on the Pharmacokinetics of Quizartinib. Li, J., Holmes, M., Kankam, M., et al.[2021]

Quizartinib is an effective treatment for patients with FLT3-ITD acute myeloid leukemia (AML), as it inhibits the FLT3 gene activity, leading to tumor cell death, and has shown promise in clinical trials for relapsed or refractory cases.

The drug has received breakthrough therapy designation from the FDA, highlighting its potential, but further studies are necessary to assess its safety, efficacy in combination with other treatments, and to address its side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quizartinib (AC220): a promising option for acute myeloid leukemia. Zhou, F., Ge, Z., Chen, B.[2020]

In a phase 1 study involving 48 healthy subjects, futibatinib, an FGFR inhibitor, did not prolong the heart's QTcF interval at either therapeutic (20 mg) or supratherapeutic (80 mg) doses, indicating a favorable cardiac safety profile.

The study demonstrated that futibatinib's effects on QTcF were minimal (less than 10 milliseconds), with no significant impact on heart rate or other ECG parameters, and no serious adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Futibatinib on Cardiac Repolarization: Results of a Randomized, Controlled, Double-Blind, QT/QTc, Phase 1 Study in Healthy Subjects. Yamamiya, I., Lester, R., Sonnichsen, D., et al.[2023]

In a study of 60 patients with advanced solid tumors, daily administration of 500 mg fedratinib did not cause clinically significant changes in QTc prolongation or other ECG parameters, indicating it is safe in this regard.

The analysis showed that fedratinib had a shallow and statistically insignificant effect on QTc intervals, with no patients experiencing clinically relevant ECG effects, aligning with its known safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Potential for QTc Prolongation With Repeated Oral Doses of Fedratinib in Patients With Advanced Solid Tumors. Ogasawara, K., Xu, C., Yin, J., et al.[2022]

In a study of 226 patients with relapsed/refractory acute myeloid leukemia, higher concentrations of quizartinib and its active metabolite AC886 were associated with a significant increase in the QT interval, with a predicted mean increase of 21.1 ms at the highest dose of 60 mg/day.

Patient factors such as age, sex, and concurrent use of QT-prolonging drugs did not significantly influence the QTcF increase, highlighting the importance of monitoring quizartinib levels, especially in patients taking strong CYP3A inhibitors, which necessitates dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concentration-QTc analysis of quizartinib in patients with relapsed/refractory acute myeloid leukemia. Kang, D., Ludwig, E., Jaworowicz, D., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11557512/

Concentration‐QTcF analysis of quizartinib in patients with ... As quizartinib does not significantly change heart rate (mean change ≤10 beats per minute; unpublished data), QTcF is usually considered a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06824168

Study Details | NCT06824168 | Evaluation of Two Dose ... This study also involves the Holter sub-study, which is designed to assess the impact of rapid acceleration in heart rate on the cardiac safety of quizartinib.

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216993Orig1s000OtherR.pdf

216993Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov Therefore, the safety of quizartinib in presence of sudden heart rate changes raised in the Complete Response Letter remains uncertain. The ...

4. vanflytahcp.com vanflytahcp.com/en/efficacy

Efficacy | VANFLYTA® (quizartinib) | HCP Of the 1,081 patients with AML treated with VANFLYTA in clinical trials, torsades de pointes occurred in approximately 0.2% of patients, cardiac arrest occurred ...

5. withpower.com withpower.com/trial/quizartinib-for-heart-rate-effects-146cb

Quizartinib for Heart Rate Effects · Info for Participants Trial Overview The study is testing the effects of a drug called Quizartinib on the electrical activity of the heart when the heart rate is quickly increased.

6. vanflytahcp.com vanflytahcp.com/en/safety

Safety Profile | VANFLYTA® (quizartinib) | HCP Of the 1,081 patients with AML treated with VANFLYTA in clinical trials, torsades de pointes occurred in approximately 0.2% of patients, cardiac arrest occurred ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3804291/

Phase I Study of Quizartinib Administered Daily to Patients ... Cardiac safety data indicated that quizartinib had a marked effect on cardiac repolarization at doses ≥ 200 mg/day. Although there was a dose- and sex ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/quizartinib-oral-route/description/drg-20554258

Quizartinib (oral route) - Side effects & dosage irregular or slow heart rate; no blood pressure; stopping of the heart; unconsciousness. Some side effects may occur that usually do not need medical attention.