Thorough QT Assessment of Cedazuridine in Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Cedazuridine; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9472NZ
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astex Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): November 15, 2021
• Study Completion (Actual): November 16, 2021

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 8, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: E7727-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes