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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment T (Therapeutic dose) | Experimental | The subjects will receive a ziresovir 125 mg as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4) |
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| Treatment ST (Supratherapeutic dose) | Experimental | The subjects will receive a ziresovir 500 mg as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4) |
|
| Treatment P (Placebo) | Placebo Comparator | The subjects will receive a placebo as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4) |
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| Treatment PC (positive control) | Active Comparator | The subjects will receive a moxifloxacin hydrochloride tablet 400 mg as single dose on Day 1 (Period 1) or Day 9 (Period 2) or Day 17 (Period 3) or Day 25 (Period 4) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ziresovir 125 mg | Drug | Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period |
| Change from baseline in HR, PR, and QRS |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Han, M.D., M.P.H | California Clinical Trials Medical Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Clinical Trials Medical Group, Inc. | Glendale | California | 91206 | United States |
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This clinical study will last for a total of 59 days, including a 26-day screening period, admission day (Day -2) preceding the first treatment period, 4 treatment periods with 8 days washout in-between and a safety follow-up period (7 ± 1 days after the last dose).
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Partially Double-Blind
| Ziresovir 500 mg | Drug | Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral |
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| Placebo | Drug | Active Substance: Placebo, Pharmaceutical Form: Suspension, Route of Administration: Oral |
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| Moxifloxacin hydrochloride tablet 400 mg | Drug | Active Substance: Moxifloxacin hydrochloride Pharmaceutical Form: Tablet Route of Administration: Oral |
|
Change-from-baseline in HR, PR and QRS (ΔHR, ΔPR and ΔQRS). |
| 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. | Up to Day 8 of each treatment period (up to 31 days) |
| Treatment-emergent changes in ECG Morphology | Treatment-emergent changes in ECG Morphology | 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. | Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period |
| Maximum observed plasma concentration (Cmax) of ziresovir | PK parameters of ziresovir and its metabolites including maximum observed plasma concentration (Cmax). | 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). | 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). | 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. |
| ID | Term |
|---|---|
| C000707852 | ziresovir |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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