This is a single-center, randomized, partially double-blind, placebo and active-controlled, 4-period crossover design thorough QT/QTc (TQT) clinical study to evaluate the effects of ziresovir on cardiac repolarization in healthy subjects.
This clinical study is a single-center, randomized, partially double-blind, placebo- and active-controlled, four-period crossover design, with healthy subjects comprising the enrolled population. Ziresovir and placebo will be administered in a double-blind manner, while moxifloxacin hydrochloride tablets will be administered in as open-label. Thirty-two subjects meeting all inclusion criteria and none of the exclusion criteria will be randomized into 1 of 12 dosing sequences, each consisting of 4 periods with an 8-day washout period in-between.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
32
Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral
Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral
Active Substance: Placebo, Pharmaceutical Form: Suspension, Route of Administration: Oral
Change from baseline QTcF (ΔQTcF)
The primary ECG endpoint is the change from baseline in the QT interval corrected for heart rate (HR) using the Fridericia method (ΔQTcF).
Time frame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
Change from baseline in QTc
Change from baseline in QTc using correction methods not chosen as the primary correction method if a substantial HR effect is observed
Time frame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
Change from baseline in HR, PR, and QRS
Change-from-baseline in HR, PR and QRS (ΔHR, ΔPR and ΔQRS).
Time frame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
Incidence of treatment-emergent adverse events (TEAEs) and changes in laboratory safety tests, vital signs, and ECGs.
Incidence of treatment-emergent adverse events (TEAEs) and changes in laboratory safety tests, vital signs, and ECGs.
Time frame: Up to Day 8 of each treatment period (up to 31 days)
Treatment-emergent changes in ECG Morphology
Treatment-emergent changes in ECG Morphology
Time frame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
Categorical outliers for QTcF/QTcI/QTcS, HR, PR, and QRS.
Categorical outliers for QTcF/QTcI/QTcS, HR, PR, and QRS.
Time frame: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Active Substance: Moxifloxacin hydrochloride Pharmaceutical Form: Tablet Route of Administration: Oral
Maximum observed plasma concentration (Cmax) of ziresovir
PK parameters of ziresovir and its metabolites including maximum observed plasma concentration (Cmax).
Time frame: Pre-dose within 1 hour and at 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, and 72 hours post-dose during each period
Terminal elimination half-life (t1/2) of ziresovir.
PK parameters of ziresovir and its metabolites including terminal elimination half-life (t1/2).
Time frame: Pre-dose within 1 hour and at 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, and 72 hours post-dose during each period.
Area under the curve (AUC) of ziresovir.
PK parameters of ziresovir and its metabolites including area under the curve (AUC).
Time frame: Pre-dose within 1 hour and at 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, and 72 hours post-dose during each period.