Thorough QT Assessment of Cedazuridine in Healthy Subjects

NCT04953923 — Phase 1, Completed, 36 participants, Astex Pharmaceuticals, Inc.

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

Registry	NCT04953923
Status	Completed
Phase	Phase 1
Study type	Interventional; randomized, crossover, masking: quadruple, basic science
Enrollment	36 (Actual)
Sponsor	Astex Pharmaceuticals, Inc. (Industry)
Conditions	Healthy Volunteers
Interventions	Cedazuridine, Placebo, Moxifloxacin (Drug)
Dates	start 2021-07-01, primary completion 2021-11-15, completion 2021-11-16, first posted 2021-07-08, last updated 2024-08-02
Locations	1 site in Netherlands

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
Treatment A	Experimental	Drug: Cedazuridine	Cedazuridine at a therapeutic dose
Treatment B	Experimental	Drug: Cedazuridine	Cedazuridine at a supratherapeutic dose
Treatment C	Placebo comparator	Drug: Placebo	Placebo control
Treatment D	Active comparator	Drug: Moxifloxacin	Moxifloxacin positive control

Cedazuridine (Drug): Tablet for oral administration
Placebo (Drug): Capsule for oral administration
Moxifloxacin (Drug): Tablet for oral administration

+Outcome measures

Primary outcomes

Change from baseline in QTcF [Baseline and Day 20]: Change from baseline in QTcF following single therapeutic and supratherapeutic doses of cedazuridine

Secondary outcomes

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

+Eligibility

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

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

+Locations (1)

Facility	City	Country	Status
PRA Health Sciences	Groningen	Netherlands