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- Ensaio Clínico NCT06591845
Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects
A Single-Center, Randomized, Partially Double-Blind, Placebo- and Active-Controlled, Four-period Crossover, Thorough QT/QTc (TQT) Clinical Study to Evaluate the Effects of Ziresovir on Cardiac Repolarization in Healthy Subjects
Visão geral do estudo
Status
Condições
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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California
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Glendale, California, Estados Unidos, 91206
- California Clinical Trials Medical Group, Inc.
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- The subject voluntarily signed a written informed consent form.
- Male or female; between 18 and 50 years old (inclusive).
- Male subjects weighing ≥50 kg, female subjects weighing ≥45 kg, body mass index (BMI) between 19.0 and 30.0 kg/m2 (inclusive), BMI= weight (kg)/height2 (m2).
- Healthy, as defined by no clinically significant or relevant abnormalities identified by vital signs, physical examination, laboratory examination items, ECG, and other trial-related examinations at screening, admission or baseline day of each period as assessed by the investigator.
- The subject can communicate well with the investigator and is able to complete the study in compliance with the protocol.
Exclusion Criteria:
- History of or evidence of clinically significant disorder, condition or disease not otherwise excluded that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- History of cardiovascular disease or risk factors for Torsade de Pointes (TdP) at screening, including but not limited to: unexplained syncope; heart failure; cardiomyopathy; hypertension; angina pectoris; myocardial infarction; hypokalemia; bradycardia or sick sinus syndrome; cardiac conduction abnormalities; personal or family history of long QT syndrome (LQTS); or family history of sudden death.
- Known or suspected malignancy.
- Known allergic reactions to study intervention (e.g., ziresovir or its drug excipients, moxifloxacin, fluoroquinolone antibiotics) or history of clinically significant multiple or severe drug allergies, food allergies.
- Subjects who have donated blood or have had a blood loss ≥500 ml within 3 months prior to screening.
- Subjects who have participated in a clinical trial evaluating an investigational drug or device within 30 days or 5 half-lives (whichever is longer) prior to screening.
- History of substance abuse (e.g., alcohol, licit or illicit drugs) within 1 year prior to screening.
- 12-lead ECG at screening or admission exceeding criteria: PR>220 ms, QRS>120 ms, HR< 50 bpm or >100 bpm, QTcF >450 ms (male and female) (The mean of 3 triplicate ECGs timepoint measurement); or ECG abnormalities that are considered by the investigator to be abnormal and clinically significant.
- Systolic blood pressure (BP) > 140 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg at screening or admission.
- Serum potassium, calcium, or magnesium levels outside the normal range at screening or admission.
- Positive blood alcohol test, positive urine cotinine test or positive urine drug abuse screening at screening or admission.
- Engaged in strenuous exercise within 48 hours before randomization (e.g., marathon running, long-distance cycling, weightlifting).
- Intake of caffeinated beverages or food within 48 hours before randomization or a history of high caffeine consumption (e.g., in the last 3 months drinking >5 cups of coffee/day).
- History of alcoholism or regular alcohol consumption within 1 year prior to screening, defined as more than 14 units (male) or 7 units (female) of alcohol per week (1 unit =360 mL of beer or 45 mL of spirits containing 40% alcohol or 150 mL of wine).
- Smoking or use of tobacco or nicotine-containing products within 6 months before screening.
- Pregnant or lactating women or those with positive blood pregnancy test results.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Treatment T (Therapeutic dose)
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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Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral
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Experimental: Treatment ST (Supratherapeutic dose)
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)
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Active Substance: Ziresovir, Pharmaceutical Form: Suspension, Route of Administration: Oral
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Comparador de Placebo: Treatment P (Placebo)
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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Active Substance: Placebo, Pharmaceutical Form: Suspension, Route of Administration: Oral
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Comparador Ativo: Treatment PC (positive control)
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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Active Substance: Moxifloxacin hydrochloride Pharmaceutical Form: Tablet Route of Administration: Oral
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline QTcF (ΔQTcF)
Prazo: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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The primary ECG endpoint is the change from baseline in the QT interval corrected for heart rate (HR) using the Fridericia method (ΔQTcF).
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Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline in QTc
Prazo: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Change from baseline in QTc using correction methods not chosen as the primary correction method if a substantial HR effect is observed
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Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Change from baseline in HR, PR, and QRS
Prazo: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Change-from-baseline in HR, PR and QRS (ΔHR, ΔPR and ΔQRS).
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Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Incidence of treatment-emergent adverse events (TEAEs) and changes in laboratory safety tests, vital signs, and ECGs.
Prazo: Up to Day 8 of each treatment period (up to 31 days)
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Incidence of treatment-emergent adverse events (TEAEs) and changes in laboratory safety tests, vital signs, and ECGs.
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Up to Day 8 of each treatment period (up to 31 days)
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Treatment-emergent changes in ECG Morphology
Prazo: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Treatment-emergent changes in ECG Morphology
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Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Categorical outliers for QTcF/QTcI/QTcS, HR, PR, and QRS.
Prazo: Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Categorical outliers for QTcF/QTcI/QTcS, HR, PR, and QRS.
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Before dosing (Baseline) through 48 hours after the dose on Day 1 in each treatment period
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Maximum observed plasma concentration (Cmax) of ziresovir
Prazo: 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
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PK parameters of ziresovir and its metabolites including maximum observed plasma concentration (Cmax).
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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
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Terminal elimination half-life (t1/2) of ziresovir.
Prazo: 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.
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PK parameters of ziresovir and its metabolites including terminal elimination half-life (t1/2).
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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.
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Area under the curve (AUC) of ziresovir.
Prazo: 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.
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PK parameters of ziresovir and its metabolites including area under the curve (AUC).
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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.
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: David Han, M.D., M.P.H, California Clinical Trials Medical Group
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- AK0529-3004
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