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: 1. Age 1 month to 36 months 2. Weight ≥ 3.5 kg 3. Diagnosis of LRTI 4. Diagnosis of RSV 5. Hospitalization due to RSV LRTI
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
51
Hospital Interzonal General de Agudos "Dr. José Penna"
Bahía Blanca, Buenos Aires, Argentina
Hospital Italiano Regional Del Sur
Bahía Blanca, Buenos Aires, Argentina
Hospital General de Ninos Pedro de Elizalde
Buenos Aires, Buenos Aires F.D., Argentina
Hospital de ninos "Ricardo Gutierrez"
Calgary, Alberta, Canada
Hospital Base San Jose Osorno
Osorno, Los Lagos Region, Chile
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP
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.
Time frame: From start of IMP on Day 1 up to Day 7
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Permanent Discontinuation of IMP
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.
Time frame: From start of IMP on Day 1 up to Day 12
Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 18 to 24 Hours Post-dose
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Time frame: Anytime between 18 to 24 hours post-dose on Day 1
Part A: Number of Participants With Abnormal Clinically Significant Physical Examination Results at 48 Hours Post-dose
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Time frame: At 48 hours post-dose on Day 1
Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results at Baseline
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Time frame: Baseline (pre-dose on Day 1)
Part B: Number of Participants With Abnormal Clinically Significant Physical Examination Results Anytime Between 40 to 48 Hours Post-dose 10
Physical examination included general appearance, HEENT, dermatologic, cardiovascular, respiratory, gastrointestinal and neurological examination. Clinical significance of results were determined by the investigator.
Time frame: Anytime between 40 to 48 hours post-dose 10 on Day 5
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose
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.
Time frame: Anytime between 4 to 5 hours post-dose on Day 1
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 12 Hours Post-Dose
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.
Time frame: At 12 hours post-dose on Day 1
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-Dose
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.
Time frame: Anytime between 18 to 24 hours post-dose on Day 1
Part A: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at 48 Hours Post-Dose
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.
Time frame: 48 hours post-dose on Day 1
Part B: Number of Participants With Abnormal Vital Signs Per Investigator's Interpretation at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose 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.
Time frame: Anytime between 4 to 5 hours post-dose 1 (Day 1)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation At Pre-dose 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 2= assessment prior to receiving dose 2 of IMP on Day 1.
Time frame: Pre-dose 2 (Day 1)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 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 3= assessment prior to receiving dose 3 of IMP on Day 2.
Time frame: Pre-dose 3 (Day 2)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 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 4= assessment prior to receiving dose 4 of IMP on Day 2.
Time frame: Pre-dose 4 (Day 2)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 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 5= assessment prior to receiving dose 5 of IMP on Day 3.
Time frame: Pre-dose 5 (Day 3)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 6
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.
Time frame: Pre-dose 6 (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
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.
Time frame: Anytime between 4 to 5 hours post-dose 6 (Day 3)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 7
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.
Time frame: Pre-dose 7 (Day 4)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 8
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.
Time frame: Pre-dose 8 (Day 4)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 9
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.
Time frame: Pre-dose 9 (Day 5)
Part B: Number of Participants With Abnormal Clinically Significant Vital Signs Per Investigator's Interpretation at Pre-dose 10
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.
Time frame: Pre-dose 10 (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
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.
Time frame: Anytime between 40 to 48 hours post-dose 10 on Day 5
Part A: Number of Participants With Abnormal Hematology Results at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part A: Number of Participants With Abnormal Hematology Results at 48 Hours Post-Dose
Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Time frame: At 48 hours post-dose on Day 1
Part B: Number of Participants With Abnormal Hematology Results at Baseline
Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Time frame: Baseline (pre-dose on Day 1)
Part B: Number of Participants With Abnormal Hematology Results Anytime Between 40 to 48 Hours Post-dose 10
Hematology parameters included basophils, eosinophils, MCHC, MCH, MCV, RBC, HCT, Hb, WBC, lymphocytes, monocytes, neutrophils and platelet count. Institutional laboratory normal ranges were used.
Time frame: Anytime between 40 to 48 hours post-dose 10 on Day 5
Part A: Number of Participants With Abnormal Clinical Chemistry Results at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part A: Number of Participants With Abnormal Clinical Chemistry Results at 48 Hours Post-Dose
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.
Time frame: At 48 hours post-dose on Day 1
Part B: Number of Participants With Abnormal Clinical Chemistry Results at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part B: Number of Participants With Abnormal Clinical Chemistry Results Anytime Between 40 to 48 Hours Post-dose 10
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.
Time frame: Anytime between 40 to 48 hours post-dose 10 on Day 5
Part A: Number of Participants With Abnormal Urinalysis Results at Baseline
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).
Time frame: Baseline (pre-dose on Day 1)
Part A: Number of Participants With Abnormal Urinalysis Results at 48 Hours Post-dose
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).
Time frame: At 48 hours post-dose on Day 1
Part B: Number of Participants With Abnormal Urinalysis Results at Baseline
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).
Time frame: Baseline (pre-dose on Day 1)
Part B: Number of Participants With Abnormal Urinalysis Results Anytime Between 40 to 48 Hours Post-Dose 10
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).
Time frame: Anytime between 40 to 48 hours post-dose 10 on Day 5
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 4 to 5 Hours Post-Dose
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.
Time frame: Anytime between 4 to 5 hours post-dose on Day 1
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation Anytime Between 18 to 24 Hours Post-dose
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.
Time frame: Anytime between 18 to 24 hours post-dose on Day 1
Part A: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at 48 Hours Post-dose
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.
Time frame: 48 hours post-dose on Day 1
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Baseline
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.
Time frame: Baseline (pre-dose on Day 1)
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
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.
Time frame: Anytime between 4 to 5 hours post-dose 1 on Day 1
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 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.
Time frame: Pre-dose 3 (Day 2)
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 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.
Time frame: Pre-dose 5 (Day 3)
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
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.
Time frame: Anytime between 4 to 5 hours post-dose 6 (Day 3)
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 8
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.
Time frame: Pre-dose 8 (Day 4)
Part B: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Results Per Investigator's Interpretation at Pre-dose 10
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.
Time frame: Pre-dose 10 (Day 5)
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
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.
Time frame: Anytime between 40 to 48 hours post-dose 10 on Day 5
Part A: Time to Maximum Plasma Concentration (Tmax)
No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the Pharmacokinetic (PK) population.
Time frame: 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)
No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
AUC(0 to 12) was calculated using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
AUC(0 to 12) was calculated using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
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Santiago, Santiago Metropolitan, Chile
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San José, Costa Rica
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San José, Costa Rica
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San José, Costa Rica
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Time frame: 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])
Area under the plasma concentration-time curve from time 0 to the last measurable concentration was determined using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.
Time frame: 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])
Area under the plasma concentration-time curve from time 0 to the last measurable concentration was determined using the linear trapezoidal method. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
AUCinf was determined as AUC(0 to t) + (Clast/kel), where Clast was the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and kel was the terminal phase rate. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
AUCinf was determined as AUC(0 to t) + (Clast/kel), where Clast was the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and kel was the terminal phase rate. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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)
Time frame: At 12 hours post-dose on Day 1
Part B: Trough Concentration at the End of Dose 6 (C12)
Time frame: At 12 hours post-dose 6
Part A: Predicted Plasma Clearance
Clearance was calculated as Dose divided by AUC(0 to inf). No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.
Time frame: 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: Predicted Plasma Clearance
Clearance was calculated as Dose divided by AUC(0 to inf). No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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
Apparent volume of distribution was estimated as Dose/Kel\*AUC(0 to inf), where Kel=apparent first-order terminal elimination rate constant. No sampling was done at pre-dose (0 hour) and pre-dose results were imputed for all participants in the PK population.
Time frame: 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
Apparent volume of distribution was estimated as Dose/Kel\*AUC(0 to inf), where Kel=apparent first-order terminal elimination rate constant. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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
Accumulation ratio was calculated as ratio of the area under the curve (AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one singe dose. No sampling was done at pre-dose (0 hour) on Day 1 and pre-dose results were imputed for all participants in the PK population.
Time frame: 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
Percentage fluctuation was calculated as 100\*(Cmax-Cmin)/Cavg, where Cmin=minimum plasma concentration and Cmax measured over dosing interval.
Time frame: 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)
AUC(0 to tau) was determined using the linear trapezoidal method.
Time frame: 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)
Cavg was estimated as AUC(0 to tau)/tau, where tau=dosing interval (12 hours).
Time frame: Day 3 Dose 6 (pre-dose, anytime between 4 to 5 hours post-dose, 12 hours post-dose)
Part B: Minimum Observed Plasma Concentration
Time frame: Day 3 Dose 6 (pre-dose)
Part B: Plasma Trough Concentration
Time frame: 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)
Percent change from baseline in log10 total RSV viral load was analyzed using a mixed effects analysis of covariance (ANCOVA) model. The model was fitted to the participants treated at the final doses selected for Cohort 5 as pre-planned in statistical analysis plan for age group \>=1 month to \<6 months.
Time frame: 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)
Percent change from baseline in log10 total RSV viral load was analyzed using a mixed effects ANCOVA model. The model was fitted to the participants treated at the final doses selected for Cohort 5 as pre-planned in statistical analysis plan for age group \>=1 month to \<6 months.
Time frame: 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
Time to resolution was calculated for RSV-related signs and symptoms that were present at study start and was defined as the time of randomization to the time that RSV-related signs and symptoms were absent.
Time frame: Up to Day 12
Part B: Time to Improvement in RSV-Related Signs and Symptoms
Time to improvement was calculated for RSV-related signs and symptoms that were classified as moderate or severe during the course of the study and was defined as the time from randomization to the time that RSV-related signs and symptoms were mild or absent.
Time frame: Up to Day 12
Part B: RSV Clinical Scoring System Scores
RSV clinical score was a composite score for infants with RSV infection \>= 1 month of age based on 4 items (respiratory rate, wheezing, retraction of respiratory muscles and general condition). Score for each item ranged from 0 to 3 where 0=none/normal and 3=severe. Total score was calculated as sum of individual items and ranged from 0 to 12, where higher score indicated severe disease. RSV symptoms were graded as mild: score \<=5, moderate: score \> 5 but \< 9 and severe: score \>=9.
Time frame: 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