Healthy Volunteers
Conditions
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.
Interventions
DRUGPlacebo
Capsule for oral administration
DRUGMoxifloxacin
Tablet for oral administration
DRUGCedazuridine
Tablet for oral administration
Sponsors
Astex Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in QTcF | Baseline and Day 20 | Change from baseline in QTcF following single therapeutic and supratherapeutic doses of cedazuridine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Participants with adverse events | Up to Day 20 | Number of participants with adverse events following single therapeutic and supratherapeutic doses of cedazuridine |
| Change from baseline in heart rate | Baseline and Day 20 | Change from baseline in heart rate following single therapeutic and supratherapeutic doses of cedazuridine |
| 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 |
| 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 |
| Change from baseline in QTcF | Baseline and Day 20 | Change from baseline in QTcF following cedazuridine-epimer and moxifloxacin administration |
| Pharmacokinetic parameter: Cmax | Up to Day 20 | Cmax is the maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin |
| Pharmacokinetic parameter: Tmax | Up to Day 20 | Tmax is the time to maximum observed plasma concentration of cedazuridine, cedazuridine-epimer, and moxifloxacin |
| 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 |
| 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 |
Countries
Netherlands
Outcome results
None listed