Thorough QT Assessment of Cedazuridine in Healthy Subjects

Astex Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: Cedazuridine; Drug: Moxifloxacin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04953923

E7727-02

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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36 participants in 4 patient groups, including a placebo group

Treatment A

Experimental group

Description:

Cedazuridine at a therapeutic dose

Treatment:

Drug: Cedazuridine

Treatment B

Experimental group

Description:

Cedazuridine at a supratherapeutic dose

Treatment:

Drug: Cedazuridine

Treatment C

Placebo Comparator group

Description:

Placebo control

Treatment:

Drug: Placebo

Treatment D

Active Comparator group

Description:

Moxifloxacin positive control

Treatment:

Drug: Moxifloxacin