Thorough QT Assessment of Cedazuridine in Healthy Subjects

Study Overview
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Brief Summary
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This study is designed to evaluate the effect of therapeutic and supratherapeutic oral doses of cedazuridine on cardiac repolarization, as detected by QTc in healthy subjects, in accordance with regulatory guidelines. Moxifloxacin will be used to validate the study. Study duration per participant is approximately 20 days.

Official Title
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A Randomized, Double-blinded, Double-dummy, Placebo-controlled Thorough QTC Study With Single Oral Doses of Cedazuridine in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Cedazuridine
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female who is not of childbearing potential Body mass index of 18.0 to 32.0 kg/m^2, inclusive Exclusion Criteria: QTcF >450 msec at screening Clinically relevant abnormalities in conduction parameters; or if PR interval > 200 msec, QRS duration > 110 msec, or bradycardia or tachycardia (HR <45 bpm or >100 bpm) History or presence of hypokalemia, hypomagnesemia, or hypocalcemia Risk factors for Torsades de Pointes (TdP) (eg, congenital deafness, heart failure, cardiomyopathy, concomitant medications known to cause QTc prolongation) within a washout of at least 30 days Family history of Long QT Syndrome or family history of TdP Sick sinus syndrome, atrioventricular block (any degree) Myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged QT interval, or conduction abnormalities Repeated or frequent syncope or vasovagal episodes Resuscitated arrest possibly due to TdP; hypertension, angina, or severe peripheral arterial circulatory disorders Use of concomitant medications that prolong the QT/QTc interval

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Cedazuridine at a therapeutic dose | Drug: Cedazuridine<br>* Tablet for oral administration<br>|
| Experimental: Treatment B<br>Cedazuridine at a supratherapeutic dose | Drug: Cedazuridine<br>* Tablet for oral administration<br>|
| Placebo Comparator: Treatment C<br>Placebo control | Drug: Placebo<br>* Capsule for oral administration<br>|
| Active Comparator: Treatment D<br>Moxifloxacin positive control | Drug: Moxifloxacin<br>* Tablet for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in QTcF | Change from baseline in QTcF following single therapeutic and supratherapeutic doses of cedazuridine | Baseline and Day 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in QTcF | Change from baseline in QTcF following cedazuridine-epimer and moxifloxacin administration | Baseline and Day 20 | 
| Safety: Participants with adverse events | Number of participants with adverse events following single therapeutic and supratherapeutic doses of cedazuridine | Up to Day 20 | 
| Change from baseline in heart rate | Change from baseline in heart rate following single therapeutic and supratherapeutic doses of cedazuridine | Baseline and Day 20 | 
| Change from baseline in PR interval of the electrocardiogram (ECG) | Change from baseline in PR interval of the ECG following single therapeutic and supratherapeutic doses of cedazuridine | Baseline and Day 20 | 
| Change from baseline in QRS interval of the electrocardiogram (ECG) | Change from baseline in QRS interval of the ECG following single therapeutic and supratherapeutic doses of cedazuridine | Baseline and Day 20 | 
| Change from baseline in T-wave morphology | Change from baseline in treatment-emergent T-wave morphology following single therapeutic and supratherapeutic doses of cedazuridine | Baseline to Day 20 | 
| Pharmacokinetic parameter: Cmax | Cmax is the maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin | Up to Day 20 | 
| Pharmacokinetic parameter: Tmax | Tmax is the time to maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin | Up to Day 20 | 
| Pharmacokinetic parameter: AUClast | Area under the curve (AUC) from time 0 to time of last measurable concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin | Up to Day 20 |