A Phase 2 Open-Label Study in Infants With REspiratory Syncytial VIRus Lower RespirAtory Tract Infection, Followed by a DoubLe-blind, Placebocontrolled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (REVIRAL 1)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 51
- 试验地点
- 59
- 主要终点
- Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP
研究概览
简要总结
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (sisunatovir). Sisunatovir is developed as potential treatment of Respiratory Syncytial Virus (RSV) infections. This study will assess sisunatovir as compared to placebo in infants aged 1 month to 36 months who are hospitalized with RSV lower respiratory tract infection (LRTI). A placebo looks like the study medicine but does not contain any active medicine in it.
This study will be conducted in 3 parts:
In Part A participants aged 6 months to 3 years will be given a single dose of 2.5 mg/kg of sisunatovir in Cohort 1. In Cohort 2, participants age 1 month to 6 months will receive a single dose of 2 mg/kg of sisunatovir only after the completion of Cohort 1. 12-24 participants will be enrolled in Part A In Part B participants age 1 month to 36 months will receive sisunatovir or placebo dosed every 12 hours for 5 days. Doses for part B will be determined after the completion of Part A. 24-40 participants will be enrolled in Part B.
The dose regimen for Part C will be determined after the completion of Part B. Approximately 120 participants age 1 month to 36 months will receive either sisunatovir or placebo.
To participate in this study participants must meet the following criteria:
- Age 1 month to 36 months
- Weight ≥ 3.5 kg
- Diagnosis of LRTI
- Diagnosis of RSV
- Hospitalization due to RSV LRTI
详细描述
This is a multicentre, 3-part study to evaluate safety, tolerability, PK, PD, and antiviral effect of single and multiple dosing of RV521 in infants hospitalised due to RSV LRTI.
The clinical study consists of 3 parts, the third part (Part C) is optional:
- Part A is an open-label, multicentre, single dose study in infants hospitalised with RSV LRTI (Cohorts 1 & 2)
- Part B is a randomised, double-blind, placebo-controlled, multicentre multiple dose study in infants hospitalised with RSV LRTI (Cohorts 3, 4 & 5)
- Part C is a randomised 1:1, double-blind, placebo-controlled, multicentre, multiple-dose study in infants hospitalised with RSV LRTI I The number of subjects enrolled in Parts A and B of the study will depend on the safety and PK data from the group of subjects enrolled in specified age cohorts and the subsequent recommendation of the Data Safety Monitoring Committee (DSMC).
The DSMC may recommend a dose adjustment (either a reduction or an escalation) and/or regimen adjustment (Part B only) for subsequent subjects because of the observation of an unexpected safety/tolerability profile and/or differences between the observed and predicted exposure resulting from a specified dose of RV521.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Month 至 36 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥ 1 month and ≤ 36 months of age
- •Weight ≥ 3.5 kg
- •Clinical diagnosis of LRTI
- •A positive RSV diagnostic test
- •Hospitalised because of RSV LRTI
- •Symptoms of LRTI must be present for no more than 1 week (Part B) and no more than 5 days (Part C) before the Screening Visit
- •Expected to remain in hospital for a minimum of 3 days
- •The parent(s)/legal guardian(s) of the subject have provided written informed consent for the subject to participate and are able and willing to comply with the study protocol
排除标准
- •Premature (gestational age less than 37 weeks) AND <1 year of post-natal age
- •Known to have significant comorbidities that would limit the ability to administer study drug or evaluate the safety or clinical response to study drug.
- •Any clinically significant ECG abnormalities.
- •Known to be immunocompromised.
- •High risk of having developing asthma.
- •Suspected of having a clinically significant bacterial infection.
- •History of renal failure.
- •Clinical evidence of hepatic decompensation
- •History of epilepsy or seizures, including febrile seizures
- •Allergy to test medication or constituents
- •Has received 1 or more doses of palivizumab at any time before Screening or received treatment with antiviral therapy for RSV (eg, ribavirin or intravenous [IV] immunoglobulin) within 3 months before the Screening Visit.
研究组 & 干预措施
RV521
sisunatovir is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. The RV521 dry powder blend will be supplied in capsules containing 10, 20, or 50 mg RV521. The Investigational Medicinal Product (IMP) will be dispersed in a defined volume of suspending diluent prior to oral administration on a mg/kg basis. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of suspending diluent prior to administration will be provided in the Pharmacy Manual.
The proposed dosing regimen for Part A is a single open label dose of RV521. Part B and C is RV521 or placebo administered BID, 12 hours apart, for a period of 5 consecutive days with a total of 10 doses. However, this is subject to the recommendation of the DSMC.
干预措施: RV521 (Drug)
Placebo
The placebo capsules administered in Part B and C will contain mannitol and microcrystalline cellulose (vehicle). The placebo dry powder will be dispersed in suspending diluent and given orally BID. Instructions for opening the capsule(s) and dispersing the contents in a fixed volume of suspending diluent prior to administration will be provided in the Pharmacy Manual.
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP
时间窗: From start of IMP on Day 1 up to Day 7
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a medicinal product which did not necessarily have a causal relationship with the IMP. TEAEs were defined as AEs which started, or worsened, after the first dose of IMP. An SAE was any untoward medical occurrence or effect that, at any dose, resulted in death; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity or other important medical event.
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP
时间窗: From start of IMP on Day 1 up to Day 12
An AE was defined as any untoward medical occurrence in a clinical study participant administered a medicinal product which did not necessarily have a causal relationship with the IMP. TEAEs were defined as AEs which started, or worsened, after the first dose of IMP. An SAE was any untoward medical occurrence or effect that, at any dose, resulted in death; was life threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity or other important medical event.
Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Physical examination included general appearance; head, eyes, ears, nose and throat (HEENT); dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 18 to 24 Hours Post-dose
时间窗: Anytime between 18 to 24 hours post-dose on Day 1
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at 48 Hours Post-dose
时间窗: At 48 hours post-dose on Day 1
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 40 to 48 Hours Post-dose 10
时间窗: Anytime between 40 to 48 hours post-dose 10 on Day 5
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Baseline
时间窗: Baseline (pre-dose on Day 1)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose
时间窗: Anytime between 4 to 5 hours post-dose on Day 1
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 12 Hours Post-Dose
时间窗: At 12 hours post-dose on Day 1
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-Dose
时间窗: Anytime between 18 to 24 hours post-dose on Day 1
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 48 Hours Post-Dose
时间窗: 48 hours post-dose on Day 1
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Vital Signs Per Investigator's Interpretation at Baseline
时间窗: Baseline (pre-dose on Day 1)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 1
时间窗: Anytime between 4 to 5 hours post-dose 1 (Day 1)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation At Pre-dose 2
时间窗: Pre-dose 2 (Day 1)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 2= assessment prior to receiving dose 2 of IMP on Day 1.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 3
时间窗: Pre-dose 3 (Day 2)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 3= assessment prior to receiving dose 3 of IMP on Day 2.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 4
时间窗: Pre-dose 4 (Day 2)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 4= assessment prior to receiving dose 4 of IMP on Day 2.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 5
时间窗: Pre-dose 5 (Day 3)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 5= assessment prior to receiving dose 5 of IMP on Day 3.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 6
时间窗: Pre-dose 6 (Day 3)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 6= assessment prior to receiving dose 6 of IMP on Day 3.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 6
时间窗: Anytime between 4 to 5 hours post-dose 6 (Day 3)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 7
时间窗: Pre-dose 7 (Day 4)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 7= assessment prior to receiving dose 7 of IMP on Day 4.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 8
时间窗: Pre-dose 8 (Day 4)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 8= assessment prior to receiving dose 8 of IMP on Day 4.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 9
时间窗: Pre-dose 9 (Day 5)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 9= assessment prior to receiving dose 9 of IMP on Day 5.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 10
时间窗: Pre-dose 10 (Day 5)
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure. Predose 10= assessment prior to receiving dose 10 of IMP on Day 5.
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 40 to 48 Hours Post-Dose 10
时间窗: Anytime between 40 to 48 hours post-dose 10 on Day 5
Vital signs included body temperature, systolic and diastolic blood pressure, respiratory rate, heart rate and pulse oximetry. Number of participants with abnormal clinically significant vital signs per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Hematology Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Hematology parameters included basophils, eosinophils, mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean cell volume (MCV), red blood cell count (RBC), hematocrit (HCT), hemoglobin (Hb), white blood cell count (WBC), lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Part A: Number of Participants With Abnormal Hematology Results at 48 Hours Post-Dose
时间窗: At 48 hours post-dose on Day 1
Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Part B: Number of Participants With Abnormal Hematology Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Part B: Number of Participants With Abnormal Hematology Results Anytime Between 40 to 48 Hours Post-dose 10
时间窗: Anytime between 40 to 48 hours post-dose 10 on Day 5
Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Part A: Number of Participants With Abnormal Clinical Chemistry Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Clinical chemistry parameters included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, calcium, chloride, creatinine, gamma glutamyltransferase (GGT), glucose, lactate dehydrogenase (LDH), potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.
Part A: Number of Participants With Abnormal Clinical Chemistry Results at 48 Hours Post-Dose
时间窗: At 48 hours post-dose on Day 1
Clinical chemistry parameters included ALT, albumin, ALP, AST, bilirubin, calcium, chloride, creatinine, GGT, glucose, LDH, potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.
Part B: Number of Participants With Abnormal Clinical Chemistry Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Clinical chemistry parameters included ALT, albumin, ALP, AST, bilirubin, calcium, chloride, creatinine, GGT, glucose, LDH, potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.
Part B: Number of Participants With Abnormal Clinical Chemistry Results Anytime Between 40 to 48 Hours Post-dose 10
时间窗: Anytime between 40 to 48 hours post-dose 10 on Day 5
Clinical chemistry parameters included ALT, albumin, ALP, AST, bilirubin, calcium, chloride, creatinine, GGT, glucose, LDH, potassium, protein, sodium and urea. Institutional laboratory normal ranges were used.
Part A: Number of Participants With Abnormal Urinalysis Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Following urine parameters were analyzed: epithelial cells (normal range: 0 to 5 cells per high power field \[hpf\]), erythrocytes (0 to 2 per hpf), granular casts (0 per low power field \[lpf\]), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and pH (5 to 8).
Part A: Number of Participants With Abnormal Urinalysis Results at 48 Hours Post-dose
时间窗: At 48 hours post-dose on Day 1
Following urine parameters were analyzed: epithelial cells (normal range: 0 to 5 cells per hpf), erythrocytes (0 to 2 per hpf), granular casts (0 per lpf), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and potential of hydrogen (pH) (5 to 8).
Part B: Number of Participants With Abnormal Urinalysis Results at Baseline
时间窗: Baseline (pre-dose on Day 1)
Following urine parameters were analyzed: epithelial cells (normal range: 0 to 5 cells per hpf), erythrocytes (0 to 2 per hpf), granular casts (0 per lpf), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and pH (5 to 8).
Part B: Number of Participants With Abnormal Urinalysis Results Anytime Between 40 to 48 Hours Post-Dose 10
时间窗: Anytime between 40 to 48 hours post-dose 10 on Day 5
Following urine parameters were analysed: epithelial cells (normal range: 0 to 5 cells per hpf), erythrocytes (0 to 2 per hpf), granular casts (0 per lpf), hyaline casts (0 to 1 per lpf), leukocytes (0 to 5 per hpf), RBC casts (0 per lpf), WBC casts (0 per lpf), waxy casts (0 per lpf) and pH (5 to 8).
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Baseline
时间窗: Baseline (pre-dose on Day 1)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QT interval corrected by Bazzett's formula (QTcB) interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose
时间窗: Anytime between 4 to 5 hours post-dose on Day 1
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-dose
时间窗: Anytime between 18 to 24 hours post-dose on Day 1
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at 48 Hours Post-dose
时间窗: 48 hours post-dose on Day 1
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Baseline
时间窗: Baseline (pre-dose on Day 1)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 1
时间窗: Anytime between 4 to 5 hours post-dose 1 on Day 1
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 3
时间窗: Pre-dose 3 (Day 2)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 5
时间窗: Pre-dose 5 (Day 3)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 6
时间窗: Anytime between 4 to 5 hours post-dose 6 (Day 3)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 8
时间窗: Pre-dose 8 (Day 4)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 10
时间窗: Pre-dose 10 (Day 5)
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 40 to 48 Hours Post-Dose 10
时间窗: Anytime between 40 to 48 hours post-dose 10 on Day 5
A 12-lead ECG was performed for assessment of following ECG parameters: ventricular heart rate, PR interval, QRS interval, QT interval and QTcB interval. Number of participants with abnormal clinically significant results for any ECG parameter per investigator's interpretation are reported in this outcome measure.
次要结局
- Part A: Predicted Plasma Clearance(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part A: Time to Maximum Plasma Concentration (Tmax)(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part B: Time to Maximum Plasma Concentration (Tmax)(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Maximum Observed Plasma Concentration (Cmax)(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part B: Maximum Observed Plasma Concentration (Cmax)(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC0-12)(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours post-dose on Day 1)
- Part B: Area Under the Plasma Concentration Time Curve From Time Zero to 12 Hours (AUC0-12)(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC[0 to t])(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part B: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUC[0 to t])(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Terminal Half-life (t1/2)(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part B: Terminal Half-life (t1/2)(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0 to Inf)(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part B: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0 to Inf)(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Trough Concentration at the End of First Dosing Interval (C12)(At 12 hours post-dose on Day 1)
- Part B: Trough Concentration at the End of Dose 6 (C12)(At 12 hours post-dose 6)
- Part B: Predicted Plasma Clearance(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part A: Apparent Volume of Distribution of the Drug After Extravascular Administration(Anytime between 4 to 5 hours, anytime between 6 to 8 hours, 12 hours, 18 to 24 hours and 48 hours post-dose on Day 1)
- Part B: Apparent Volume of Distribution of the Drug After Extravascular Administration(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part B: Accumulation Ratio(Day 1 Dose 1 (anytime between 4 to 5 hours post-dose, 12 hours post-dose), Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part B: Percentage Fluctuation(Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part B: Area Under the Plasma Concentration Time Curve From Time Zero to the End of Last Dosing Interval (AUC0-tau)(Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part B: Average Plasma Concentration Over Dosing Interval (Cavg)(Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose))
- Part B: Minimum Observed Plasma Concentration(Day 3 Dose 6 (pre-dose))
- Part B: Plasma Trough Concentration(Day 3 Dose 6 (pre-dose))
- Part B: Percent Change From Baseline in Logarithm to Base10 (Log10) Total RSV Viral Load by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR)(Baseline (pre-dose on Day 1), 60 hours and 156 hours after first dose on Day 1)
- Part B: Percent Change From Baseline in Logarithm to Base10 (Log10) Total RSV Viral Load by Cell-Based Infectivity Assay (CBIA)(Baseline (pre-dose on Day 1), 60 hours and 156 hours after first dose on Day 1)
- Part B: Time to Resolution of RSV-Related Signs and Symptoms(Up to Day 12)
- Part B: Time to Improvement in RSV-Related Signs and Symptoms(Up to Day 12)
- Part B: RSV Clinical Scoring System Scores(Baseline (pre-dose 1 on Day 1), pre-dose 3, pre-dose 5, pre-dose 7, pre-dose 9, anytime between 40 to 48 hours post-dose 10 on Day 5)