Thorough QT Assessment of Cedazuridine in Healthy Subjects

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04953923
• Other study ID #: E7727-02
• Status: Completed
• Phase: Phase 1
• Start date: July 1, 2021
• Est. completion date: November 16, 2021

Study information

• Verified date: August 2022
• Source: Astex Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 16, 2021
• Est. primary completion date: November 15, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Cedazuridine
Tablet for oral administration
• Placebo
Capsule for oral administration
• Moxifloxacin
Tablet for oral administration

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals, Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in QTcF	Change from baseline in QTcF following single therapeutic and supratherapeutic doses of cedazuridine	Baseline and Day 20
Secondary	Change from baseline in QTcF	Change from baseline in QTcF following cedazuridine-epimer and moxifloxacin administration	Baseline and Day 20
Secondary	Safety: Participants with adverse events	Number of participants with adverse events following single therapeutic and supratherapeutic doses of cedazuridine	Up to Day 20
Secondary	Change from baseline in heart rate	Change from baseline in heart rate following single therapeutic and supratherapeutic doses of cedazuridine	Baseline and Day 20
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetic parameter: Cmax	Cmax is the maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin	Up to Day 20
Secondary	Pharmacokinetic parameter: Tmax	Tmax is the time to maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin	Up to Day 20
Secondary	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