Clinical Results Summary
A clinical study to understand the effects of ketoconazole andfluconazole on the plasma levels of quizartinib in healthy participantsProtocol number: AC220-015

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for quizartinib, also known as AC220. Each participant helped toadvance medical research for people affected with acute myeloid leukemia. Their
contribution to medicine and healthcare is greatly appreciated.

Important note: This summary only shows the results of a single study. Other studies may have differentfindings. Researchers and health authorities look at the results of many studies to understand which
treatments work and how they work. It takes a lot of people in many studies around the world to advance
medical science and healthcare.
Do not use the results of this study to make health decisions. Please talk to a doctor before changing any
treatment you are taking or if you have any questions about these study results.

What was the main purpose of this study?
Quizartinib is an investigational drug that is being tested to treat people with a type of blood cancer called
acute myeloid leukemia, or AML. AML is a cancer of the blood and the bone marrow.
Ketoconazole and fluconazole are drugs already available in the market for treating fungal infections. Bothketoconazole and fluconazole block a protein in the liver called CYP3A4 that breaks down quizartinib in thebody. Ketoconazole is a strong inhibitor of CYP3A4 and fluconazole is a moderate inhibitor of CYP3A4. Taking
either ketoconazole or fluconazole with quizartinib may slow down the breakdown of quizartinib in the body.
If quizartinib is not broken down, it may accumulate in the body and cause harmful effects. AC886 is abreakdown product of quizartinib. It can be formed as a result of quizartinib being broken down by CYP3A4.
AC886 has similar effects in the body to quizartinib. Once formed from quizartinib, AC886 can also be further
broken down by CYP3A4.
In this study, researchers wanted to understand the effects of ketoconazole and fluconazole on the plasma*levels of quizartinib and its breakdown product AC886 in healthy participants.
* Plasma is the fluid part of the blood. It contains different components of the blood that are necessary for lifeand health such as hormones, proteins, etc.

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Treatments given in this study
The treatments given in this study were:AC220-015 Clinical Results Summary | 2

Main purpose of this study
The main question the researchers wanted to answer in this study was:Other purpose of this study
Researchers also wanted to answer the following questions:• What side effects could the participants develop during the study?
There were some additional questions that researchers wanted to answer but these are not discussed in thissummary.

How long was this study?
An individual participant could have been in this study forabout 2 months.
The study was completed as planned and a study report
was created. This summary is based on that report.

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Who was in this study?
This study included 93 participants from the United States. Healthy men and women could take part in thisstudy if they:•were 18 to 55 years of age,

•were of average body size and weight,•

had normal healthy kidneys and liver asmeasured by different blood tests,•

were using effective birth control methods
during the study or were unable to havechildren,•were willing to eat high-potassium foods, suchas bananas, for at least 24 hours before taking
quizartinib,•

were able to communicate in English, and•were able to follow the study requirements.

What happened during this study?
This was a Phase 1 study. Phase 1 studies are done to find out how a new study treatment works in a small
number of participants. This Phase 1 study helped researchers understand what happens to quizartinib in thebody and if other drugs such as ketoconazole or fluconazole change quizartinib plasma levels.
This study was “open label”. This means that both the researchers and the participants knew which treatment
was given to which participants.
Participants were randomly assigned to 1 of the 3 treatment groups using a computer system. This process iscalled randomization. It means that each participant could be assigned to any treatment group to make surethe groups are distributed fairly.

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Participants were assigned to one of the following treatment groups:•Ketoconazole 200 milligrams (mg) twice daily, taken by mouth.

•Fluconazole 200 mg twice daily, taken by mouth.

• Placebo twice daily, taken by mouth.
Participants took placebo, ketoconazole, or fluconazole twice daily from Day 1 to Day 28. Participants in all
3 treatment groups also took a single 30 mg dose of quizartinib only on Day 8.

What were the key results of this study?
Key results from this study are shown for each group of participants as average results. This summary does notshow the results from each individual participant. An individual participant’s results could be different fromthe total group of participants.

What was the effect of ketoconazole and fluconazole on the plasma levels of
quizartinib and its active breakdown product AC886 in healthy participants?
To answer this question, the researchers collected blood samples from the participants at defined timepoints
over a period of time. They measured the levels of quizartinib and AC886 in the participants’ plasma duringthe study.

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Over time, participants who took quizartinib with ketoconazole had higher levels of quizartinib and slightly
lower levels of AC886 in their plasma compared to participants who took quizartinib and placebo.
Participants who took quizartinib with fluconazole had similar levels of quizartinib and AC886 in their plasmacompared to participants who took quizartinib and placebo.

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What were the other results of this study?
What side effects did the participants develop during the study?
Side effects are medical problems that happened during the study, which the study doctor (investigator)
thought could be related to the treatments in the study.
Side effects are considered serious if they cause death, are life-threatening, cause disability, cause lasting
problems, cause birth defects, or require hospitalization.
Side effects other than those related to study treatment* are not reported here.
*If a side effect occurred before Day 8, the study treatment was ketoconazole or fluconazole. If the side effectoccurred on or after Day 8, the study treatment was ketoconazole and quizartinib or fluconazole andquizartinib or placebo and quizartinib. Placebo looks like the study treatment but does not have any medicine
in it.
There were no serious side effects or deaths reported during this study. None of the participants in the study
stopped treatment early because of side effects.

How many participants had side effects?
The side effects experienced by participants in any group are reported below:

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* 3 participants in the placebo + quizartinib group had 6 different side effects between them and 1 participant
in the fluconazole + quizartinib group had 2 different side effects.
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How was this study useful for patients and researchers?
This study helped researchers understand the effect of ketoconazole and fluconazole on the plasma levels of
quizartinib and its breakdown product AC886 in healthy participants. The study results also helped informresearchers of the effects of drugs similar to ketoconazole and fluconazole on quizartinib and AC886 plasmalevels.
Findings from this study may be used in other studies. Other studies for quizartinib are ongoing.
Please remember, this summary only shows the results of a single study. Other studies may have differentfindings. Please talk to a doctor before changing any treatment you are taking or if you have any questions
about these study results.

Where can I learn more about this study?
If you were a study participant and have questions about the results of this study, please speak with thedoctor or staff at your study site.
Full study title: A phase 1, open-label,randomized, placebo controlled, parallel groupstudy to evaluate the effect of ketoconazole andfluconazole on the pharmacokinetics ofquizartinib and its active metabolite, AC886, inhealthy volunteers.

Sponsor: Daiichi Sankyo, Inc.
Sponsor contact information:
211 Mount Airy Road, Basking Ridge, NJ 07920
Email: CTRInfo@dsi.com
Phone number: 1-908-992-6640
Date of this summary: 09 February 2022

This summary was prepared by Kinapse Ltd, a Syneos Health® company.

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