Thorough QT Assessment of Cedazuridine in Healthy Subjects
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
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
- 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
- Change from baseline in QTcF [Baseline and Day 20]
Change from baseline in QTcF following cedazuridine-epimer and moxifloxacin administration
- 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 T-wave morphology [Baseline to Day 20]
Change from baseline in treatment-emergent T-wave morphology following single therapeutic and supratherapeutic doses of cedazuridine
- 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
Eligibility Criteria
Criteria
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.- E7727-02