Thorough QT Assessment of Cedazuridine in Healthy Subjects

NCT04953923 | Completed Phase 1 FDA Drug

• 1 other identifier: E7727-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Change from baseline in QTcF

  Change from baseline in QTcF following single therapeutic and supratherapeutic doses of cedazuridine

  Baseline and Day 20

Secondary Outcomes (9)

• Change from baseline in QTcF

  Baseline and Day 20

• Safety: Participants with adverse events

  Up to Day 20

• Change from baseline in heart rate

  Baseline and Day 20

• Change from baseline in PR interval of the electrocardiogram (ECG)

  Baseline and Day 20

• Change from baseline in QRS interval of the electrocardiogram (ECG)

  Baseline and Day 20

Study Arms (4)

Treatment A

EXPERIMENTAL

Cedazuridine at a therapeutic dose

Drug: Cedazuridine

Treatment B

EXPERIMENTAL

Cedazuridine at a supratherapeutic dose

Drug: Cedazuridine

Treatment C

PLACEBO COMPARATOR

Placebo control

Drug: Placebo

Treatment D

ACTIVE COMPARATOR

Moxifloxacin positive control

Drug: Moxifloxacin

Interventions

Cedazuridine DRUG

Tablet for oral administration

Treatment A; Treatment B

Placebo DRUG

Capsule for oral administration

Treatment C

Moxifloxacin DRUG

Tablet for oral administration

Treatment D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female who is not of childbearing potential
• Body mass index of 18.0 to 32.0 kg/m\^2, inclusive

You may not qualify if:

• 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

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (1)

PRA Health Sciences

Groningen, 9472NZ, Netherlands

Location

MeSH Terms

Interventions

cedazuridine; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 8, 2021
• Study Start: July 1, 2021
• Primary Completion: November 15, 2021
• Study Completion: November 16, 2021
• Last Updated: August 2, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)