Thorough QT Assessment of Cedazuridine in Healthy Subjects

Sponsor
Astex Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04953923
Collaborator
(none)
36
1
4
4.5
7.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
A Randomized, Double-blinded, Double-dummy, Placebo-controlled Thorough QTC Study With Single Oral Doses of Cedazuridine in Healthy Subjects
Actual Study Start Date :
Jul 1, 2021
Actual Primary Completion Date :
Nov 15, 2021
Actual Study Completion Date :
Nov 16, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Change from baseline in QTcF [Baseline and Day 20]

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

Secondary Outcome Measures

  1. Change from baseline in QTcF [Baseline and Day 20]

    Change from baseline in QTcF following cedazuridine-epimer and moxifloxacin administration

  2. Safety: Participants with adverse events [Up to Day 20]

    Number of participants with adverse events following single therapeutic and supratherapeutic doses of cedazuridine

  3. Change from baseline in heart rate [Baseline and Day 20]

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

  4. 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

  5. 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

  6. 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

  7. Pharmacokinetic parameter: Cmax [Up to Day 20]

    Cmax is the maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin

  8. Pharmacokinetic parameter: Tmax [Up to Day 20]

    Tmax is the time to maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin

  9. 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 Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 PRA Health Sciences Groningen Netherlands 9472NZ

Sponsors and Collaborators

  • Astex Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Astex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04953923
Other Study ID Numbers:
  • E7727-02
First Posted:
Jul 8, 2021
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 12, 2022