Influenza, Human
Conditions
Keywords
pandemic, seasonal influenza, Influenza B virus, H1N1, zanamivir, Influenza A virus, H1N1 Subtype, Relenza, influenza, neuraminidase inhibitor
Brief summary
The purpose of this study is to determine whether zanamivir aqueous solution given by intravenous injection is safe in treating hospitalized patients with confirmed influenza infection. A single arm open-label design has been selected to achieve the primary objective of providing regulatory authorities with safety data on IV zanamivir.
Detailed description
This study will be an open-label, Phase II, multi-center, single arm study to evaluate the safety and tolerability of IV zanamivir 600mg twice daily for 5 days in hospitalized subjects with laboratory confirmed influenza infection. The initial 5-day treatment course may be extended for up to 5 additional days if viral shedding is determined to be ongoing or if clinical symptoms warrant further treatment with IV zanamivir. Approximately 200 subjects will be enrolled into the study (approximately 150 adult/adolescent subjects and approximately 50 pediatric subjects). Adult (\>/= 18 years of age) with normal renal function will receive 600mg per dose. Pediatric (6 months to \<13 years)/adolescent (\>13 years to \<18 years) subjects will receive an age-adjusted, weight-based dose (not to exceed the 600 mg adult dose) intended to provide comparable systemic exposures to 600mg in adults. Subjects with renal impairment will receive an adjusted dose based on calculated creatinine clearance and renal replacement modality. Serum pharmacokinetic assessments will be performed in subjects across all age groups wherever possible. Pharmacokinetic analyses will be conducted, in real-time to the extent possible, when 4 subjects (from whom samples can be obtained) are enrolled in each of the following age cohorts: 6 months to less than 1 year; 1 to less than 2 years, and 2 to less than 6 years to determine the need for pediatric dose adjustments. PK assessments are required in the first 4 subjects enrolled in the 6 months to less than 1 year age cohort, and PK data must be analyzed and IV zanamivir dosage must be reviewed before additional subjects in this age cohort can be enrolled. The study duration is approximately 28 days for subjects whose treatment duration is 5 days, and up to approximately 33 days for subjects whose treatment duration is extended to a maximum of 10 days. The study will consist of Pre-dose Baseline Assessments (Day 1), During Treatment Assessments (Days 1 to 5, and up to Day 10), and Follow-up Assessments on the following days: Post-Treatment +2 +5, +9, +16 and +23 Days. If the first dose of IV zanamivir is administered in the afternoon/evening of Day 1, the twice daily dosing schedule will result in one treatment day encompassing two calendar days. For subjects who have been discharged from hospital, the Post-Treatment +2, +5, +9 and +16 Days Assessments can be made by telephone contact.
Interventions
DRUGzanamivir aqueous solution
Zanamivir aqueous solution 10mg/mL is a clear, colorless, single use, sterile non-preserved preparation containing 10mg of zanamivir in each milliliter, and made isotonic with sodium chloride. It is presented in 20mL clear glass vials closed with rubber stoppers. Each vial contains 200mg of zanamivir.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged greater than or equal to 6 months of age; a female is eligible to enter and participate in the study if she is: 1. of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, 2. of child-bearing potential, has a negative pregnancy test at Baseline, and agrees to one of the following methods for avoidance of pregnancy during the study and until the Post-Treatment +23 Days Follow-up Assessment: * Abstinence; or, * Oral contraceptive, either combined or progestogen alone; or, * Injectable progestogen; or, * Implants of levonorgestrel; or, * Estrogenic vaginal ring; or, * Percutaneous contraceptive patches; or * Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected failure rate is less than 1% per year as stated in the IUD or IUS Product Label; or, * Has a male partner who is sterilized; or, * Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository). * Subjects who have confirmed influenza as determined by a positive result in a rapid test for influenza A or influenza B, or a laboratory test for influenza including influenza virus antigen test, virus culture or RT-PCR test. Subjects with negative rapid test result suspected of having influenza can be enrolled following confirmatory testing by RT-PCR, antigen test or culture. * Hospitalized subjects with symptomatic influenza * Subjects who are able to receive their first dose of study medication within seven days of experiencing influenza-like symptoms. * Subjects willing and able to adhere to the procedures stated in the protocol. * Subjects/legally acceptable representative (LAR) of minors and unconscious adults willing and able to give written informed consent to participate in the study (or included as permitted by local regulatory authorities, IRBs/IECs or local laws). * French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. * UK subjects and subjects in Spain: Subjects should be in a high dependency or intensive care setting at the time of enrollment and either have severe and progressive illness on approved influenza antivirals, or are considered unsuitable for treatment with approved influenza antivirals. * Subjects who have severe or progressive influenza illness on approved (fully licensed) influenza antivirals, or who are considered unsuitable or inappropriate for treatment with approved influenza antivirals, or who in the opinion of the investigator may benefit from IV zanamivir therapy.
Exclusion criteria
* Subjects who, in the opinion of the investigator, are not likely to survive the next 48 hours beyond Baseline. * Subjects who require concurrent therapy with another influenza antiviral drug. * Subjects who have participated in a study using an investigational influenza antiviral drug within 30 days prior to Baseline. * Subjects who are known or suspected to be hypersensitive to any component of the study medication. * Subjects who meet the following criteria at Baseline: * ALT greater than or equal to 3xULN and bilirubin greater than or equal to 2xULN or ALT greater than or equal to 5xULN * History of cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the Investigator, will interfere with the safety of the individual subject. * Child in care (CiC) as defined below: A child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a CiC can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a CiC does not include a child who is adopted or has an appointed legal guardian. * French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days. * Females who are pregnant (positive urine or serum pregnancy test at Baseline) or are breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | Up to post-treatment (PT) + 23 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. All AEs were assesed by the Investigateor as related or not related to the study treatment. |
| Number of Participants With Any Severe or Grade 3/4 AEs | Up to post-treatment (PT) + 23 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. |
| Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | Up to post-treatment (PT) + 23 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assesed by the Investigateor as related or not related to the study treatment. |
| Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | Up to 10 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. |
| Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | Up to post-treatment (PT) + 23 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. |
| Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | Blood samples for laboratory assessments were collected at Baseline (Day \[D\] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Clinical chemistry parameters included alanine aminotransferase (ALT), direct bilirubin (DB), total bilirubin (TB), and creatinine. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated clinical chemistry parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | Blood samples for laboratory assessments were collected at Baseline (Day \[D\] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Hematology parameters included hemoglobin, total neutrophils (TN), and white blood cell (WBC) count. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated hematology parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | Up to post-treatment (PT) + 23 days | A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included ALT, TB, and creatinine. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Up to post-treatment (PT) + 23 days | A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, TN, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Median Heart Rate at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | Heart rate was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Heart rate was assessed once daily during inpatient or outpatient follow-up visits. Heart rate values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). |
| Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | SBP and DBP were measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. SBP and DBP were assessed once daily during inpatient or outpatient follow-up visits. SBP and DBP values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). |
| Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | TCPO2 is a noninvasive test that directly measures the oxygen level of tissue beneath the skin. Because oxygen is carried to tissues by blood flow in the arteries, TCPO2 is an indirect measure of blood flow. The percent (%) oxygen saturation was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Oxygen saturation was assessed once daily during inpatient follow-up visits. The median oxygen saturation values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). |
| Median Respiration Rate at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | Respiration rate was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Respiration rate was assessed once daily during inpatient or outpatient follow-up visits. The median respiration rate at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). |
| Median Body Temperature at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | Body temperature was recorded at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Body temperature was recorded once daily during inpatient or outpatient follow-up visits. Median body temperature at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). |
| Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Baseline (Day 1) | The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles). |
| Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | Baseline (Day 1) and Day 5 | Twelve-lead ECGs were recorded for the parameters of QTcF and QTcB. The first set of pre-dose ECG values at Baseline (Day 1) and the pre-dose ECG values at Day 5 are presented. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). NA indicates that data are not available/analysis was not performed. Cohort 1 QTcF and QTcB minimum values of 0.0 were data entry errors that could not be addressed after Data Base Freeze. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Serum Clearance of Zanamivir | Day 1 and Days 3, 4, or 5 | The serum clearance of zanamivir was evaluated. Clearance is defined as the volume of zanamivir per unit time eliminated from serum. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr \>=80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed. |
| Median Time to Virologic Improvement | Up to post-treatment (PT) + 23 days | Time to virologic improvement is defined as a 2-log drop in viral load or undetectable viral ribonucleic acid (RNA) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples (PCR positive at Baseline). Only those participants available at the specified time points were analyzed. |
| Geometric Mean Volume of Distribution (Vd) of Zanamivir | Day 1 and Days 3, 4, or 5 | The Vd of zanamivir was evaluated. Volume of distribution is defined as the apparent volume in which zanamivir is distributed. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr \>= 80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed. |
| Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days | Change from Baseline in viral load was measured from nasopharyngeal swab samples, as determined by RT-PCR (PCR positive at Baseline). Nasopharyngeal swab samples were collected at Baseline (Day 1); Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10; and, only if the participants had continued symptoms and were hospitalized, post-treatment (PT) samples were collected at +2 days, +5 days, +9 days, +16 days, and +23 days. 'PT +23 days' also comprises viral load values at early study withdrawal. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles). NA indicates that data are not available/analysis was not performed. |
| Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | Baseline and up to post-treatment (PT) + 23 days | Viral susceptibility to zanamivir at Baseline and at all post-Baseline visits collectively was assessed by neuraminidase (NA) enzyme inhibition assay. The mean IC50 data are summarized by subtype (A/H1N1, A/H3N2, B) and by visit. IC50 is defined as the concentration of zanamvir required to inhibit NA activity by 50%. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data are not available/analysis was not performed. Please note: pediatric data are pending and will be updated when available. |
| Number of Participants With Treatment-emergent (TE) Mutations | Baseline and up to post-treatment (PT) + 23 days | Viral RNA isolated from participants at Baseline (Day 1) and post-Baseline visits were sequenced to determine the presence of TE neuraminidase (NA) and hemagglutinin (HA) mutations resulting from selective pressure. A mutation was considered to be TE if it was not present at Baseline and was present in the last post-Baseline sample analyzed.These mutations were classified as either known to confer zanamvir resistance or novel mutations with unknown clinical significance. Please note: pediatric data are pending and will be updated when available. |
| Median Time to Resolution of Individual Vital Signs | Up to post-treatment (PT) + 23 days | Times to return to afebrile status (normal body temperature), normal respiratory status, normal heart rate, and normal systolic blood pressure were assessed. Afebrile status is defined as a temperature \<=36.6 axilla, \<=37.2 oral, or \<=37.7 rectal, core or typanic, degrees Centigrade. A return to normal respiratory status is defined as either: (a) return to pre-morbid oxygen requirement; or (b) return to no need for supplemental oxygen; or (c) respiratory rate \<=60, \<=40, \<=34, \<=30, \<=24 or \<=24 breaths/minute (without supplemental oxygen) for Cohorts 1-6 respectively . A normal HR is defined as \<=160, \<=150, \<=140, \<=120, \<=100 or \<=100 bpm for Cohorts 1-6 respectively, and a normal SBP is defined as \>=70, \>=74, \>=76, \>=80, \>=90 or \>=90 mmHg for Cohorts 1-6 respectively. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles). |
| Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Up to post-treatment (PT) + 23 days | Ventilation status was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Ventilation status was assessed once daily during inpatient follow-up visits. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD) at any time (AT) on study and at Baseline (Day 1) are summarized. |
| Duration of Mechanical Ventilation and Supplemental Oxygen Use | Up to discharge from the hospital | Due to the conditional nature of data collection post treatment, the duration of mechanical ventilation and supplemental oxygen use were not determined. |
| Median Time to Return to Pre-morbid Functional Status | Up to post-treatment (PT) + 23 days | Time to return to pre-morbid functional status was assessed on a 3-point scale (bed rest, limited ambulation, or unrestricted). Only those participants available at the specified time points were analyzed. |
| Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Day 14 and Day 28 | The number of participants who died on or before Study Day 14 and Study Day 28 was summarized. Only those participants available at the specified time points were analyzed. |
| Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | Up to post-treatment (PT) + 23 days | Sustained resolution of the following vital signs (composite) was assessed: afebrile status, normal oxygen saturation, normal respiratory status, normal HR, and normal BP. Clinical response is defined as the resolution of at least four of five vital signs within the following resolution criteria, maintained for 24 hours or hospital discharge, whichever occurred first: Temperature in degrees Centigrade (\<=36.6 axilla, \<=37.2 oral, \<=37.7 rectal, core or tympanic); oxygen saturation (\>=95%, without supplemental oxygen); respiratory status (return to pre-morbid oxygen requirement, or no need for supplemental oxygen, or respiratory rate \<=60, \<=40, \<=34, \<=30, \<=24 or \<=24 breaths/minute without supplemental oxygen for Cohorts 1-6 respectively); HR (\<=160, \<=150, \<=140, \<=120, \<=100 or \<=100 bpm for Cohorts 1-6 respectively); SBP (\>=70, \>=74, \>=76, \>=80, \>=90 or \>=90 mmHg for Cohorts 1-6 respectively). Only those participants available at the specified time points were analyzed. |
| Number of Participants With Any AE Categorized as an Influenza Complication | Up to post-treatment (PT) + 23 days | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. |
| Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | Up to post-treatment (PT) + 23 days | Concomitant medications (prescription and non-prescription) were permitted during the course of the study at the Investigator's discretion (except for prohibited medications: during the treatment period with IV zanamivir, other influenza antiviral drugs were not permitted). The number of participants who were treated with antibiotics for influenza complications was summarized. |
| Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Up to discharge from hospital | The duration of hospitalization (H) reflects the number of hospitalization days between the date of the first dose of investigational product and the date of discharge. ICU stay includes total duration in ICU and may include days in ICU before entry into the study. For participants with a missing discharge date who were not discharged at the end of the study, the date of discharge was imputed to the last follow-up visit (post-treatment +23 days). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). |
| Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | Day 1 and Days 3, 4, or 5 | The Cmax of zanamivir was evaluated at the end of infusion. Serial blood samples for pharmacokinetic (PK) analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants who were neither on extracorporeal membrane oxygenation (ECMO) nor on continuous renal replacement therapy (CRRT), who were with CLcr \>=80 mL/minutes (\>=80mL/minute/1.73m\^2 for cohorts 1-4) and who received an initial dose (ID) and a maintenance dose (MD) of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed. |
| Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | Day 1 and Days 3, 4, or 5 | The AUC(0-tau) during the repeat dose interval and AUC(0-inf) for the initial dose were evaluated. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr \>=80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed. |
| Geometric Mean Terminal Half Life (t1/2) of Zanamivir | Day 1 and Days 3, 4, or 5 | The t1/2 of zanamivir was evaluated. Terminal half life is defined as the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Day 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr\>=80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed. |
Countries
Australia, Brazil, Canada, France, Hong Kong, Japan, Norway, Russia, South Africa, Spain, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
Male or female participants who were \>=6 months of age, hospitalized with laboratory-confirmed influenza, and able to receive study drug within 7 days of influenza symptom onset were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 6: Adults (18 Years and Older) Participants \>=18 years of age received 600 mg zanamivir by IV infusion over 30 minutes twice daily, adjusted for renal function, for 5 days. Treatment could have been extended for up to 5 additional days if viral shedding or clinical symptoms warranted further treatment. | 130 |
| Cohort 1: Infants (6 Months to <1 Year of Age) Participants 6 months to \<1 year of age received 14 mg per kilogram (mg/kg) zanamivir by IV infusion over 30 minutes twice daily, adjusted for renal function, for 5 days. Treatment could have been extended for up to 5 additional days if viral shedding or clinical symptoms warranted further treatment. | 7 |
| Cohort 2: Children (1 to <2 Years of Age) Participants 1 year to \<2 years of age received 14 mg/kg zanamivir by IV infusion over 30 minutes twice daily, adjusted for renal function, for 5 days. Treatment could have been extended for up to 5 additional days if viral shedding or clinical symptoms warranted further treatment. | 11 |
| Cohort 3: Children (2 to <6 Years of Age) Participants 2 years to \<6 years of age received 14 mg/kg zanamivir with a maximum dose of 600 mg by IV infusion over 30 minutes twice daily, adjusted for renal function, for 5 days. Treatment could have been extended for up to 5 additional days if viral shedding or clinical symptoms warranted further treatment. | 12 |
| Cohort 4: Children (6 to <13 Years of Age) Participants 6 years to \<13 years of age received 12 mg/kg zanamivir with a maximum dose of 600 mg by IV infusion over 30 minutes twice daily, adjusted for renal function, for 5 days. Treatment could have been extended for up to 5 additional days if viral shedding or clinical symptoms warranted further treatment. | 27 |
| Cohort 5: Adolescents (13 to <18 Years of Age) Participants 13 to \<18 years of age received 12 mg/kg zanamivir with a maximum dose of 600 mg by IV infusion over 30 minutes twice daily, adjusted for renal function, for 5 days. Treatment could have been extended for up to 5 additional days if viral shedding or clinical symptoms warranted further treatment. | 14 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 20 | 0 | 1 | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 5: Adolescents (13 to <18 Years of Age) | Cohort 4: Children (6 to <13 Years of Age) | Cohort 3: Children (2 to <6 Years of Age) | Cohort 2: Children (1 to <2 Years of Age) | Cohort 1: Infants (6 Months to <1 Year of Age) | Cohort 6: Adults (18 Years and Older) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.81 Years STANDARD_DEVIATION 23.796 | 15.36 Years STANDARD_DEVIATION 1.151 | 8.67 Years STANDARD_DEVIATION 1.861 | 3.74 Years STANDARD_DEVIATION 1.201 | 1.33 Years STANDARD_DEVIATION 0.22 | 0.76 Years STANDARD_DEVIATION 0.127 | 48.30 Years STANDARD_DEVIATION 16.19 |
| Race/Ethnicity, Customized African American/African Heritage | 23 participants | 3 participants | 4 participants | 1 participants | 4 participants | 1 participants | 10 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 4 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 3 participants | 0 participants | 0 participants | 2 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 10 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 10 participants |
| Race/Ethnicity, Customized Mixed Race | 3 participants | 0 participants | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Unknown | 3 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 8 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 6 participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 145 participants | 11 participants | 18 participants | 7 participants | 7 participants | 5 participants | 97 participants |
| Sex: Female, Male Female | 80 Participants | 6 Participants | 9 Participants | 4 Participants | 4 Participants | 1 Participants | 56 Participants |
| Sex: Female, Male Male | 121 Participants | 8 Participants | 18 Participants | 8 Participants | 7 Participants | 6 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 100 / 130 | 4 / 7 | 7 / 11 | 8 / 12 | 20 / 27 | 9 / 14 |
| serious Total, serious adverse events | 44 / 130 | 1 / 7 | 2 / 11 | 0 / 12 | 8 / 27 | 4 / 14 |
Outcome results
Primary
Median Body Temperature at Baseline (Day 1) and Day 5
Body temperature was recorded at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Body temperature was recorded once daily during inpatient or outpatient follow-up visits. Median body temperature at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 37.30 Degrees centigrade |
| Cohort 6: Adults (18 Years and Older) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 37.00 Degrees centigrade |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 37.15 Degrees centigrade |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 37.30 Degrees centigrade |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 37.0 Degrees centigrade |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 36.8 Degrees centigrade |
| Cohort 2: Children (1 to <2 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 37.3 Degrees centigrade |
| Cohort 2: Children (1 to <2 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 36.8 Degrees centigrade |
| Cohort 3: Children (2 to <6 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 37.5 Degrees centigrade |
| Cohort 3: Children (2 to <6 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 37.3 Degrees centigrade |
| Cohort 4: Children (6 to <13 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 37.3 Degrees centigrade |
| Cohort 4: Children (6 to <13 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 37.1 Degrees centigrade |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 37.1 Degrees centigrade |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Body Temperature at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 37.5 Degrees centigrade |
Primary
Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5
Twelve-lead ECGs were recorded for the parameters of QTcF and QTcB. The first set of pre-dose ECG values at Baseline (Day 1) and the pre-dose ECG values at Day 5 are presented. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). NA indicates that data are not available/analysis was not performed. Cohort 1 QTcF and QTcB minimum values of 0.0 were data entry errors that could not be addressed after Data Base Freeze.
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 400.6 Milliseconds |
| Cohort 6: Adults (18 Years and Older) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 406.6 Milliseconds |
| Cohort 6: Adults (18 Years and Older) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 424.0 Milliseconds |
| Cohort 6: Adults (18 Years and Older) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 422.0 Milliseconds |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 434.0 Milliseconds |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 432.0 Milliseconds |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 413.5 Milliseconds |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 405.5 Milliseconds |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 412.00 Milliseconds |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | NA Milliseconds |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 356.00 Milliseconds |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | NA Milliseconds |
| Cohort 2: Children (1 to <2 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 362.00 Milliseconds |
| Cohort 2: Children (1 to <2 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 373.00 Milliseconds |
| Cohort 2: Children (1 to <2 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 422.00 Milliseconds |
| Cohort 2: Children (1 to <2 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 416.00 Milliseconds |
| Cohort 3: Children (2 to <6 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 365.00 Milliseconds |
| Cohort 3: Children (2 to <6 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 444.00 Milliseconds |
| Cohort 3: Children (2 to <6 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 394.00 Milliseconds |
| Cohort 3: Children (2 to <6 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 410.00 Milliseconds |
| Cohort 4: Children (6 to <13 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 353.00 Milliseconds |
| Cohort 4: Children (6 to <13 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 387.50 Milliseconds |
| Cohort 4: Children (6 to <13 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 422.50 Milliseconds |
| Cohort 4: Children (6 to <13 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 380.00 Milliseconds |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 415.00 Milliseconds |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Baseline, n=87, 42, 6, 9, 11, 24, 13 | 387.00 Milliseconds |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcF, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 389.00 Milliseconds |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 | QTcB, Day 5, n=68, 40, 0, 1, 3, 3, 5 | 399.00 Milliseconds |
Primary
Median Heart Rate at Baseline (Day 1) and Day 5
Heart rate was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Heart rate was assessed once daily during inpatient or outpatient follow-up visits. Heart rate values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 93.00 Beats per minute (bpm) |
| Cohort 6: Adults (18 Years and Older) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 87.00 Beats per minute (bpm) |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 95.00 Beats per minute (bpm) |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 93.50 Beats per minute (bpm) |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 119.0 Beats per minute (bpm) |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 127.0 Beats per minute (bpm) |
| Cohort 2: Children (1 to <2 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 144.0 Beats per minute (bpm) |
| Cohort 2: Children (1 to <2 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 122.5 Beats per minute (bpm) |
| Cohort 3: Children (2 to <6 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 115.5 Beats per minute (bpm) |
| Cohort 3: Children (2 to <6 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 112.0 Beats per minute (bpm) |
| Cohort 4: Children (6 to <13 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 112.0 Beats per minute (bpm) |
| Cohort 4: Children (6 to <13 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 102.0 Beats per minute (bpm) |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 99.0 Beats per minute (bpm) |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Heart Rate at Baseline (Day 1) and Day 5 | Day 5, n=73, 42, 7, 6, 9, 15, 10 | 79.5 Beats per minute (bpm) |
Primary
Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5
TCPO2 is a noninvasive test that directly measures the oxygen level of tissue beneath the skin. Because oxygen is carried to tissues by blood flow in the arteries, TCPO2 is an indirect measure of blood flow. The percent (%) oxygen saturation was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Oxygen saturation was assessed once daily during inpatient follow-up visits. The median oxygen saturation values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 97.00 Percentage of oxygen level in blood |
| Cohort 6: Adults (18 Years and Older) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 97.00 Percentage of oxygen level in blood |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 96.00 Percentage of oxygen level in blood |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 96.00 Percentage of oxygen level in blood |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 98.0 Percentage of oxygen level in blood |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 100.0 Percentage of oxygen level in blood |
| Cohort 2: Children (1 to <2 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 95.5 Percentage of oxygen level in blood |
| Cohort 2: Children (1 to <2 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 100.0 Percentage of oxygen level in blood |
| Cohort 3: Children (2 to <6 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 98.0 Percentage of oxygen level in blood |
| Cohort 3: Children (2 to <6 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 97.0 Percentage of oxygen level in blood |
| Cohort 4: Children (6 to <13 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 98.0 Percentage of oxygen level in blood |
| Cohort 4: Children (6 to <13 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 97.0 Percentage of oxygen level in blood |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 97.5 Percentage of oxygen level in blood |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 | Day 5, n=70, 43, 7, 6, 9, 15, 9 | 96.0 Percentage of oxygen level in blood |
Primary
Median Respiration Rate at Baseline (Day 1) and Day 5
Respiration rate was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Respiration rate was assessed once daily during inpatient or outpatient follow-up visits. The median respiration rate at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 20.00 Breaths per minute |
| Cohort 6: Adults (18 Years and Older) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 23.00 Breaths per minute |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 23.50 Breaths per minute |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 22.00 Breaths per minute |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 32.0 Breaths per minute |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 40.0 Breaths per minute |
| Cohort 2: Children (1 to <2 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 34.0 Breaths per minute |
| Cohort 2: Children (1 to <2 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 31.0 Breaths per minute |
| Cohort 3: Children (2 to <6 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 30.0 Breaths per minute |
| Cohort 3: Children (2 to <6 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 29.5 Breaths per minute |
| Cohort 4: Children (6 to <13 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 20.0 Breaths per minute |
| Cohort 4: Children (6 to <13 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 23.0 Breaths per minute |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 5, n=67, 42, 7, 6, 9, 15, 10 | 19.0 Breaths per minute |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Respiration Rate at Baseline (Day 1) and Day 5 | Day 1, n=87, 43, 7, 11, 12, 27, 14 | 21.0 Breaths per minute |
Primary
Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5
SBP and DBP were measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. SBP and DBP were assessed once daily during inpatient or outpatient follow-up visits. SBP and DBP values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 70.00 Millimeters of mercury (mmHg) |
| Cohort 6: Adults (18 Years and Older) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 126.00 Millimeters of mercury (mmHg) |
| Cohort 6: Adults (18 Years and Older) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 68.00 Millimeters of mercury (mmHg) |
| Cohort 6: Adults (18 Years and Older) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 128.00 Millimeters of mercury (mmHg) |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 118.00 Millimeters of mercury (mmHg) |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 132.00 Millimeters of mercury (mmHg) |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 63.00 Millimeters of mercury (mmHg) |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 66.00 Millimeters of mercury (mmHg) |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 60.0 Millimeters of mercury (mmHg) |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 102.0 Millimeters of mercury (mmHg) |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 103.0 Millimeters of mercury (mmHg) |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 53.0 Millimeters of mercury (mmHg) |
| Cohort 2: Children (1 to <2 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 60.0 Millimeters of mercury (mmHg) |
| Cohort 2: Children (1 to <2 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 60.0 Millimeters of mercury (mmHg) |
| Cohort 2: Children (1 to <2 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 100.0 Millimeters of mercury (mmHg) |
| Cohort 2: Children (1 to <2 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 98.0 Millimeters of mercury (mmHg) |
| Cohort 3: Children (2 to <6 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 67.0 Millimeters of mercury (mmHg) |
| Cohort 3: Children (2 to <6 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 117.0 Millimeters of mercury (mmHg) |
| Cohort 3: Children (2 to <6 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 105.5 Millimeters of mercury (mmHg) |
| Cohort 3: Children (2 to <6 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 58.0 Millimeters of mercury (mmHg) |
| Cohort 4: Children (6 to <13 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 110.0 Millimeters of mercury (mmHg) |
| Cohort 4: Children (6 to <13 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 108.0 Millimeters of mercury (mmHg) |
| Cohort 4: Children (6 to <13 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 57.0 Millimeters of mercury (mmHg) |
| Cohort 4: Children (6 to <13 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 68.0 Millimeters of mercury (mmHg) |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 108.5 Millimeters of mercury (mmHg) |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | SBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 107.0 Millimeters of mercury (mmHg) |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 5, n=73, 43, 7, 5, 9, 15, 10 | 54.5 Millimeters of mercury (mmHg) |
| Cohort 5: Adolescents (13 to <18 Years of Age) | Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 | DBP, Day 1, n=87, 43, 7, 11, 12, 27, 14 | 62.0 Millimeters of mercury (mmHg) |
Primary
Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1)
The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles).
Time frame: Baseline (Day 1)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal NCS, n=128, 7, 10, 12, 25, 13 | 57 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Normal, n=128, 7, 10, 12, 25, 13 | 68 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal CS, n=128, 7, 10, 12, 25, 13 | 7 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal NCS, n=128, 7, 10, 12, 25, 13 | 2 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Normal, n=128, 7, 10, 12, 25, 13 | 5 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal CS, n=128, 7, 10, 12, 25, 13 | 0 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal NCS, n=128, 7, 10, 12, 25, 13 | 2 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Normal, n=128, 7, 10, 12, 25, 13 | 7 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal CS, n=128, 7, 10, 12, 25, 13 | 1 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal NCS, n=128, 7, 10, 12, 25, 13 | 4 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Normal, n=128, 7, 10, 12, 25, 13 | 8 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal CS, n=128, 7, 10, 12, 25, 13 | 0 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal NCS, n=128, 7, 10, 12, 25, 13 | 5 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Normal, n=128, 7, 10, 12, 25, 13 | 20 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal CS, n=128, 7, 10, 12, 25, 13 | 0 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Normal, n=128, 7, 10, 12, 25, 13 | 8 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal CS, n=128, 7, 10, 12, 25, 13 | 0 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) | Abnormal NCS, n=128, 7, 10, 12, 25, 13 | 5 Participants |
Primary
Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Time frame: Up to 10 days
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | 17 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE | 2 Participants |
Primary
Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Time frame: Up to post-treatment (PT) + 23 days
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | 20 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants Who Were Permanently Discontinued From the Study Due to an AE | 5 Participants |
Primary
Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. All AEs were assesed by the Investigateor as related or not related to the study treatment.
Time frame: Up to post-treatment (PT) + 23 days
Population: Safety Population: participants who received \>=1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | 28 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment | 5 Participants |
Primary
Number of Participants With Any Severe or Grade 3/4 AEs
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening.
Time frame: Up to post-treatment (PT) + 23 days
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Any Severe or Grade 3/4 AEs | 57 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With Any Severe or Grade 3/4 AEs | 23 Participants |
Primary
Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assesed by the Investigateor as related or not related to the study treatment.
Time frame: Up to post-treatment (PT) + 23 days
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | 16 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With Any Severe or Grade 3/4 Treatment-related AE | 2 Participants |
Primary
Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5
Blood samples for laboratory assessments were collected at Baseline (Day \[D\] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Clinical chemistry parameters included alanine aminotransferase (ALT), direct bilirubin (DB), total bilirubin (TB), and creatinine. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated clinical chemistry parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H DB, n=83, 60 | 17 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H ALT, n=129, 71 | 48 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L ALT, n=129, 71 | 1 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H ALT, n=102, 45 | 41 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N ALT, n=102, 45 | 60 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L ALT, n=102, 45 | 1 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N ALT, n=129, 71 | 79 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N DB, n=83, 60 | 61 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L DB, n=83, 60 | 2 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H DB, n=70, 36 | 20 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N DB, n=70, 36 | 46 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L DB, n=70, 36 | 1 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H TB, n=128, 71 | 11 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N TB, n=128, 71 | 110 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L TB, n=128, 71 | 7 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H TB, n=102, 42 | 13 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N TB, n=102, 42 | 85 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L TB, n=102, 42 | 4 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H Creatinine, n=128, 71 | 27 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N Creatinine, n=128, 71 | 50 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L Creatinine, n=128, 71 | 51 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H Creatinine, n=111, 46 | 31 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N Creatinine, n=111, 46 | 46 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L Creatinine, n=111, 46 | 34 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N Creatinine, n=111, 46 | 34 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H TB, n=128, 71 | 13 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H ALT, n=129, 71 | 21 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N ALT, n=129, 71 | 49 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H Creatinine, n=128, 71 | 6 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L ALT, n=129, 71 | 1 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N TB, n=128, 71 | 50 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H ALT, n=102, 45 | 16 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H Creatinine, n=111, 46 | 7 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N ALT, n=102, 45 | 27 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L TB, n=128, 71 | 7 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L ALT, n=102, 45 | 1 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N Creatinine, n=128, 71 | 56 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H DB, n=83, 60 | 9 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H TB, n=102, 42 | 6 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N DB, n=83, 60 | 45 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L Creatinine, n=111, 46 | 5 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L DB, n=83, 60 | 3 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N TB, n=102, 42 | 32 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H DB, n=70, 36 | 4 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L Creatinine, n=128, 71 | 9 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N DB, n=70, 36 | 28 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L TB, n=102, 42 | 2 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L DB, n=70, 36 | 1 Participants |
Primary
Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5
Blood samples for laboratory assessments were collected at Baseline (Day \[D\] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Hematology parameters included hemoglobin, total neutrophils (TN), and white blood cell (WBC) count. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated hematology parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline (Day 1) and Day 5
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H Hemoglobin, n=130, 71 | 0 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N Hemoglobin, n=130, 71 | 48 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L Hemoglobin, n=130, 71 | 82 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H Hemoglobin, n=114, 47 | 1 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N Hemoglobin, n=114, 47 | 25 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L Hemoglobin, n=114, 47 | 88 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H TN, n=123, 70 | 51 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N TN, n=123, 70 | 59 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L TN, n=123, 70 | 13 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H TN, n=106, 45 | 49 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N TN, n=106, 45 | 49 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L TN, n=106, 45 | 8 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H WBC Count, n=130, 71 | 29 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N WBC Count, n=130, 71 | 71 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L WBC Count, n=130, 71 | 30 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H WBC Count, n=114, 47 | 50 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N WBC Count, n=114, 47 | 49 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L WBC Count, n=114, 47 | 15 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N WBC Count, n=130, 71 | 42 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H Hemoglobin, n=130, 71 | 1 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H TN, n=106, 45 | 20 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N Hemoglobin, n=130, 71 | 30 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L WBC Count, n=114, 47 | 5 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L Hemoglobin, n=130, 71 | 40 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N TN, n=106, 45 | 18 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H Hemoglobin, n=114, 47 | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L WBC Count, n=130, 71 | 20 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N Hemoglobin, n=114, 47 | 16 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L TN, n=106, 45 | 7 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, L Hemoglobin, n=114, 47 | 31 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, N WBC Count, n=114, 47 | 30 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H TN, n=123, 70 | 34 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, H WBC Count, n=130, 71 | 9 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, N TN, n=123, 70 | 29 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 5, H WBC Count, n=114, 47 | 12 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 | D 1, L TN, n=123, 70 | 7 Participants |
Primary
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities
A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included ALT, TB, and creatinine. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Up to post-treatment (PT) + 23 days
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | TB, Grade 3, n=127, 69 | 3 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | ALT, Grade 3, n=128, 69 | 10 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | ALT, Grade 4, n=128, 69 | 5 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | TB, Grade 4, n=127, 69 | 3 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | Creatinine, Grade 3, n=129, 69 | 6 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | Creatinine, Grade 4, n=129, 69 | 5 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | Creatinine, Grade 3, n=129, 69 | 3 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | TB, Grade 4, n=127, 69 | 4 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | ALT, Grade 3, n=128, 69 | 1 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | Creatinine, Grade 4, n=129, 69 | 2 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | ALT, Grade 4, n=128, 69 | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities | TB, Grade 3, n=127, 69 | 1 Participants |
Primary
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, TN, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Up to post-treatment (PT) + 23 days
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, Grade 4, n=129, 69 | 9 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | TN, Grade 4, n=122, 68 | 1 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, Grade 3, n=129, 69 | 40 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | WBC count, Grade 3, n=129, 69 | 2 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | WBC count, Grade 4, n=129, 69 | 2 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | TN, Grade 3, n=122, 68 | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | WBC count, Grade 4, n=129, 69 | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, Grade 3, n=129, 69 | 12 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | Hemoglobin, Grade 4, n=129, 69 | 2 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | TN, Grade 3, n=122, 68 | 3 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | TN, Grade 4, n=122, 68 | 2 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities | WBC count, Grade 3, n=129, 69 | 1 Participants |
Secondary
Duration of Mechanical Ventilation and Supplemental Oxygen Use
Due to the conditional nature of data collection post treatment, the duration of mechanical ventilation and supplemental oxygen use were not determined.
Time frame: Up to discharge from the hospital
Population: ITT-E Population
Secondary
Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir
The AUC(0-tau) during the repeat dose interval and AUC(0-inf) for the initial dose were evaluated. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr \>=80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed.
Time frame: Day 1 and Days 3, 4, or 5
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 600 mg, CLcr>=80, n=63,0,0,0,0,5 | 82.86 Micrograms*hour per milliliter | Geometric Coefficient of Variation 36 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 12 mg/kg, CLcr>=80, n=0,0,0,0,8,1 | NA Micrograms*hour per milliliter | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 14 mg/kg, CLcr>=80, n=0,3,4,9,0,0 | NA Micrograms*hour per milliliter | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 600 mg, CLcr>=80, n=65,0,0, 0,0,2 | 90.33 Micrograms*hour per milliliter | Geometric Coefficient of Variation 36 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 12 mg/kg, CLcr>=80, n=0,0,0,0,4,0 | NA Micrograms*hour per milliliter | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 14 mg/kg, CLcr>=80, n=0,0,1,4,0,0 | NA Micrograms*hour per milliliter | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 12 mg/kg, CLcr>=80, n=0,0,0,0,8,1 | NA Micrograms*hour per milliliter | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 600 mg, CLcr>=80, n=65,0,0, 0,0,2 | NA Micrograms*hour per milliliter | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 14 mg/kg, CLcr>=80, n=0,0,1,4,0,0 | NA Micrograms*hour per milliliter | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 600 mg, CLcr>=80, n=63,0,0,0,0,5 | NA Micrograms*hour per milliliter | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 14 mg/kg, CLcr>=80, n=0,3,4,9,0,0 | 75.31 Micrograms*hour per milliliter | Geometric Coefficient of Variation 23 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 12 mg/kg, CLcr>=80, n=0,0,0,0,4,0 | NA Micrograms*hour per milliliter | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 14 mg/kg, CLcr>=80, n=0,0,1,4,0,0 | 68.20 Micrograms*hour per milliliter | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 12 mg/kg, CLcr>=80, n=0,0,0,0,4,0 | NA Micrograms*hour per milliliter | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 600 mg, CLcr>=80, n=65,0,0, 0,0,2 | NA Micrograms*hour per milliliter | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 14 mg/kg, CLcr>=80, n=0,3,4,9,0,0 | 72.42 Micrograms*hour per milliliter | Geometric Coefficient of Variation 14 |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 600 mg, CLcr>=80, n=63,0,0,0,0,5 | NA Micrograms*hour per milliliter | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 12 mg/kg, CLcr>=80, n=0,0,0,0,8,1 | NA Micrograms*hour per milliliter | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 600 mg, CLcr>=80, n=65,0,0, 0,0,2 | NA Micrograms*hour per milliliter | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 12 mg/kg, CLcr>=80, n=0,0,0,0,8,1 | NA Micrograms*hour per milliliter | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 14 mg/kg, CLcr>=80, n=0,3,4,9,0,0 | 80.28 Micrograms*hour per milliliter | Geometric Coefficient of Variation 38 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 14 mg/kg, CLcr>=80, n=0,0,1,4,0,0 | 81.02 Micrograms*hour per milliliter | Geometric Coefficient of Variation 28 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 12 mg/kg, CLcr>=80, n=0,0,0,0,4,0 | NA Micrograms*hour per milliliter | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 600 mg, CLcr>=80, n=63,0,0,0,0,5 | NA Micrograms*hour per milliliter | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 600 mg, CLcr>=80, n=63,0,0,0,0,5 | NA Micrograms*hour per milliliter | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 12 mg/kg, CLcr>=80, n=0,0,0,0,4,0 | 90.33 Micrograms*hour per milliliter | Geometric Coefficient of Variation 45 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 12 mg/kg, CLcr>=80, n=0,0,0,0,8,1 | 107.21 Micrograms*hour per milliliter | Geometric Coefficient of Variation 41 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 14 mg/kg, CLcr>=80, n=0,3,4,9,0,0 | NA Micrograms*hour per milliliter | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 600 mg, CLcr>=80, n=65,0,0, 0,0,2 | NA Micrograms*hour per milliliter | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 14 mg/kg, CLcr>=80, n=0,0,1,4,0,0 | NA Micrograms*hour per milliliter | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 600 mg, CLcr>=80, n=65,0,0, 0,0,2 | 64.52 Micrograms*hour per milliliter | Geometric Coefficient of Variation 30 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 14 mg/kg, CLcr>=80, n=0,3,4,9,0,0 | NA Micrograms*hour per milliliter | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 12 mg/kg, CLcr>=80, n=0,0,0,0,4,0 | NA Micrograms*hour per milliliter | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-tau), MD, 14 mg/kg, CLcr>=80, n=0,0,1,4,0,0 | NA Micrograms*hour per milliliter | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 12 mg/kg, CLcr>=80, n=0,0,0,0,8,1 | 135.22 Micrograms*hour per milliliter | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir | AUC(0-inf), ID, 600 mg, CLcr>=80, n=63,0,0,0,0,5 | 91.07 Micrograms*hour per milliliter | Geometric Coefficient of Variation 27 |
Secondary
Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion
The Cmax of zanamivir was evaluated at the end of infusion. Serial blood samples for pharmacokinetic (PK) analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants who were neither on extracorporeal membrane oxygenation (ECMO) nor on continuous renal replacement therapy (CRRT), who were with CLcr \>=80 mL/minutes (\>=80mL/minute/1.73m\^2 for cohorts 1-4) and who received an initial dose (ID) and a maintenance dose (MD) of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed.
Time frame: Day 1 and Days 3, 4, or 5
Population: PK Parameter Population: participants with one or more estimated zanamivir PK parameters
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Micrograms per mL | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 14 mg/kg, CLcr>=80, n=0, 4, 5, 9, 0, 0 | NA Micrograms per mL | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Micrograms per mL | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 6 | 32.77 Micrograms per mL | Geometric Coefficient of Variation 34 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 9, 3 | NA Micrograms per mL | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 600 mg, CLcr>=80, n=72, 0, 0, 0, 0, 2 | 35.30 Micrograms per mL | Geometric Coefficient of Variation 32 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Micrograms per mL | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 6 | NA Micrograms per mL | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 14 mg/kg, CLcr>=80, n=0, 4, 5, 9, 0, 0 | 36.21 Micrograms per mL | Geometric Coefficient of Variation 21 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Micrograms per mL | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 9, 3 | NA Micrograms per mL | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 600 mg, CLcr>=80, n=72, 0, 0, 0, 0, 2 | NA Micrograms per mL | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 14 mg/kg, CLcr>=80, n=0, 4, 5, 9, 0, 0 | 37.78 Micrograms per mL | Geometric Coefficient of Variation 24 |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 38.01 Micrograms per mL | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 9, 3 | NA Micrograms per mL | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 6 | NA Micrograms per mL | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 600 mg, CLcr>=80, n=72, 0, 0, 0, 0, 2 | NA Micrograms per mL | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Micrograms per mL | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 6 | NA Micrograms per mL | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Micrograms per mL | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 43.19 Micrograms per mL | Geometric Coefficient of Variation 9 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 600 mg, CLcr>=80, n=72, 0, 0, 0, 0, 2 | NA Micrograms per mL | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 14 mg/kg, CLcr>=80, n=0, 4, 5, 9, 0, 0 | 41.54 Micrograms per mL | Geometric Coefficient of Variation 23 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 9, 3 | NA Micrograms per mL | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 14 mg/kg, CLcr>=80, n=0, 4, 5, 9, 0, 0 | NA Micrograms per mL | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | 45.18 Micrograms per mL | Geometric Coefficient of Variation 48 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 600 mg, CLcr>=80, n=72, 0, 0, 0, 0, 2 | NA Micrograms per mL | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Micrograms per mL | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 9, 3 | 44.16 Micrograms per mL | Geometric Coefficient of Variation 47 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 6 | NA Micrograms per mL | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Micrograms per mL | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 6 | 34.47 Micrograms per mL | Geometric Coefficient of Variation 27 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 9, 3 | 4.99 Micrograms per mL | Geometric Coefficient of Variation 3997 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | ID, 14 mg/kg, CLcr>=80, n=0, 4, 5, 9, 0, 0 | NA Micrograms per mL | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 600 mg, CLcr>=80, n=72, 0, 0, 0, 0, 2 | 25.73 Micrograms per mL | Geometric Coefficient of Variation 52 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Micrograms per mL | — |
Secondary
Geometric Mean Serum Clearance of Zanamivir
The serum clearance of zanamivir was evaluated. Clearance is defined as the volume of zanamivir per unit time eliminated from serum. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr \>=80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed.
Time frame: Day 1 and Days 3, 4, or 5
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Serum Clearance of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA mL per minutes | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Serum Clearance of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | NA mL per minutes | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Serum Clearance of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA mL per minutes | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Serum Clearance of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | 110.71 mL per minutes | Geometric Coefficient of Variation 36 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Serum Clearance of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | 120.68 mL per minutes | Geometric Coefficient of Variation 36 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Serum Clearance of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA mL per minutes | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Serum Clearance of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA mL per minutes | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Serum Clearance of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA mL per minutes | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Serum Clearance of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | 27.31 mL per minutes | Geometric Coefficient of Variation 32 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Serum Clearance of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA mL per minutes | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Serum Clearance of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA mL per minutes | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Serum Clearance of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA mL per minutes | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | 31.00 mL per minutes | Geometric Coefficient of Variation 12 |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 31.78 mL per minutes | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA mL per minutes | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA mL per minutes | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA mL per minutes | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA mL per minutes | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA mL per minutes | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 40.35 mL per minutes | Geometric Coefficient of Variation 35 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA mL per minutes | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA mL per minutes | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | 41.95 mL per minutes | Geometric Coefficient of Variation 37 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA mL per minutes | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | NA mL per minutes | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | 46.70 mL per minutes | Geometric Coefficient of Variation 47 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA mL per minutes | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | 68.61 mL per minutes | Geometric Coefficient of Variation 34 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA mL per minutes | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA mL per minutes | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA mL per minutes | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | 109.83 mL per minutes | Geometric Coefficient of Variation 27 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | 53.70 mL per minutes | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | NA mL per minutes | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | 155.03 mL per minutes | Geometric Coefficient of Variation 30 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Serum Clearance of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA mL per minutes | — |
Secondary
Geometric Mean Terminal Half Life (t1/2) of Zanamivir
The t1/2 of zanamivir was evaluated. Terminal half life is defined as the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Day 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr\>=80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed.
Time frame: Day 1 and Days 3, 4, or 5
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 5 | 2.39 Hours | Geometric Coefficient of Variation 31 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 5, 9, 0, 0 | NA Hours | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Hours | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Hours | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Hours | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 600 mg, CLcr>=80, n=68, 0, 0, 0, 0, 2 | 2.56 Hours | Geometric Coefficient of Variation 34 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Hours | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 5 | NA Hours | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Hours | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 600 mg, CLcr>=80, n=68, 0, 0, 0, 0, 2 | NA Hours | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Hours | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 5, 9, 0, 0 | 1.84 Hours | Geometric Coefficient of Variation 19 |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 5 | NA Hours | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Hours | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 1.68 Hours | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 5, 9, 0, 0 | 2.49 Hours | Geometric Coefficient of Variation 118 |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 600 mg, CLcr>=80, n=68, 0, 0, 0, 0, 2 | NA Hours | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Hours | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 1.76 Hours | Geometric Coefficient of Variation 20 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Hours | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 600 mg, CLcr>=80, n=68, 0, 0, 0, 0, 2 | NA Hours | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 5 | NA Hours | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Hours | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 5, 9, 0, 0 | 1.60 Hours | Geometric Coefficient of Variation 34 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 5 | NA Hours | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | 2.57 Hours | Geometric Coefficient of Variation 55 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 600 mg, CLcr>=80, n=68, 0, 0, 0, 0, 2 | NA Hours | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Hours | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | 1.81 Hours | Geometric Coefficient of Variation 41 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 5, 9, 0, 0 | NA Hours | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 5, 9, 0, 0 | NA Hours | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 600 mg, CLcr>=80, n=67, 0, 0, 0, 0, 5 | 2.06 Hours | Geometric Coefficient of Variation 47 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | 2.16 Hours | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 600 mg, CLcr>=80, n=68, 0, 0, 0, 0, 2 | 1.73 Hours | Geometric Coefficient of Variation 21 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 4, 0 | NA Hours | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Terminal Half Life (t1/2) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Hours | — |
Secondary
Geometric Mean Volume of Distribution (Vd) of Zanamivir
The Vd of zanamivir was evaluated. Volume of distribution is defined as the apparent volume in which zanamivir is distributed. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr \>= 80 mL/minutes (\>=80 mL/minute/1.73m\^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to \<6 years of age), 12 mg/kg, not to exceed 600 mg (6 to \<18 years of age) or 600 mg zanamivir (\>=18 years of age) (represented by n=X in the category titles) were summarized. NA indicates that data are not available/analysis was not performed.
Time frame: Day 1 and Days 3, 4, or 5
Population: PK Parameter Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Liters (L) | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | NA Liters (L) | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 0 | NA Liters (L) | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | 24.89 Liters (L) | Geometric Coefficient of Variation 27 |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Liters (L) | — |
| Cohort 6: Adults (18 Years and Older) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | 24.61 Liters (L) | Geometric Coefficient of Variation 32 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Liters (L) | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA Liters (L) | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | 3.77 Liters (L) | Geometric Coefficient of Variation 12 |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 0 | NA Liters (L) | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Liters (L) | — |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA Liters (L) | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | 3.94 Liters (L) | Geometric Coefficient of Variation 29 |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 3.77 Liters (L) | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Liters (L) | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA Liters (L) | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA Liters (L) | — |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 0 | NA Liters (L) | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA Liters (L) | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 0 | NA Liters (L) | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | 5.23 Liters (L) | Geometric Coefficient of Variation 32 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA Liters (L) | — |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | 5.15 Liters (L) | Geometric Coefficient of Variation 20 |
| Cohort 2: Children (1 to <2 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | NA Liters (L) | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | NA Liters (L) | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | NA Liters (L) | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | NA Liters (L) | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Liters (L) | — |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | 9.21 Liters (L) | Geometric Coefficient of Variation 48 |
| Cohort 3: Children (2 to <6 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 0 | 9.82 Liters (L) | Geometric Coefficient of Variation 8 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 14 mg/kg, CLcr>=80, n=0, 0, 1, 4, 0, 0 | NA Liters (L) | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 600 mg, CLcr>=80, n=63, 0, 0, 0, 0, 5 | 18.57 Liters (L) | Geometric Coefficient of Variation 26 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 1 | 10.09 Liters (L) | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | ID, 14 mg/kg, CLcr>=80, n=0, 3, 4, 9, 0, 0 | NA Liters (L) | — |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 600 mg, CLcr>=80, n=65, 0, 0, 0, 0, 0 | 23.20 Liters (L) | Geometric Coefficient of Variation 25 |
| Cohort 4: Children (6 to <13 Years of Age) | Geometric Mean Volume of Distribution (Vd) of Zanamivir | MD, 12 mg/kg, CLcr>=80, n=0, 0, 0, 0, 8, 0 | NA Liters (L) | — |
Secondary
Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively
Viral susceptibility to zanamivir at Baseline and at all post-Baseline visits collectively was assessed by neuraminidase (NA) enzyme inhibition assay. The mean IC50 data are summarized by subtype (A/H1N1, A/H3N2, B) and by visit. IC50 is defined as the concentration of zanamvir required to inhibit NA activity by 50%. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data are not available/analysis was not performed. Please note: pediatric data are pending and will be updated when available.
Time frame: Baseline and up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | A/H1N1, Day 1, n=22, 2 | 0.2091 Nanomolar (nM) | Standard Deviation 0.06886 |
| Cohort 6: Adults (18 Years and Older) | Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | A/H1N1, All Post-Baseline, n=8, 1 | 0.1800 Nanomolar (nM) | Standard Deviation 0.04 |
| Cohort 6: Adults (18 Years and Older) | Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | A/H3N2, Day 1, n=5, 16 | 0.2660 Nanomolar (nM) | Standard Deviation 0.08385 |
| Cohort 6: Adults (18 Years and Older) | Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | A/H3N2, All Post-Baseline, n=2, 3 | 0.2300 Nanomolar (nM) | Standard Deviation 0.01414 |
| Cohort 6: Adults (18 Years and Older) | Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | B, Day 1, n=2, 16 | 1.6100 Nanomolar (nM) | Standard Deviation 0.35355 |
| Cohort 6: Adults (18 Years and Older) | Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively | B, All Post-Baseline, n=0, 10 | NA Nanomolar (nM) | — |
Secondary
Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points
Change from Baseline in viral load was measured from nasopharyngeal swab samples, as determined by RT-PCR (PCR positive at Baseline). Nasopharyngeal swab samples were collected at Baseline (Day 1); Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10; and, only if the participants had continued symptoms and were hospitalized, post-treatment (PT) samples were collected at +2 days, +5 days, +9 days, +16 days, and +23 days. 'PT +23 days' also comprises viral load values at early study withdrawal. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles). NA indicates that data are not available/analysis was not performed.
Time frame: Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days
Population: ITT-E Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 10, n=19, 0, 2, 1, 4, 1 | -1.75 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +2 days, n=32, 0, 1, 2, 6, 3 | -1.38 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +5 days, n=26, 0, 2, 0, 5, 2 | -1.84 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +23 days, n=21, 2, 4, 0, 4, 0 | -2.89 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 3, n=82, 4, 7, 10, 15, 7 | -1.42 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 4, n=84, 0, 0, 2, 2, 1 | -1.59 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +16 days, n=21, 0, 1, 0, 4, 1 | -2.48 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 5, n=75, 5, 4, 8, 12, 5 | -1.57 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 2, n=89, 0, 0, 2, 3, 2 | -0.92 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 7, n=23, 1, 1, 1, 3, 1 | -1.58 Log10 copies per milliliter |
| Cohort 6: Adults (18 Years and Older) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +9 days, n=27, 0, 1, 0, 3, 2 | -2.58 Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +9 days, n=27, 0, 1, 0, 3, 2 | NA Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 3, n=82, 4, 7, 10, 15, 7 | -1.655 Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +16 days, n=21, 0, 1, 0, 4, 1 | NA Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 10, n=19, 0, 2, 1, 4, 1 | NA Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 4, n=84, 0, 0, 2, 2, 1 | NA Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +23 days, n=21, 2, 4, 0, 4, 0 | -4.455 Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 7, n=23, 1, 1, 1, 3, 1 | -1.820 Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 5, n=75, 5, 4, 8, 12, 5 | -2.720 Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +5 days, n=26, 0, 2, 0, 5, 2 | NA Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +2 days, n=32, 0, 1, 2, 6, 3 | NA Log10 copies per milliliter |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 2, n=89, 0, 0, 2, 3, 2 | NA Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +2 days, n=32, 0, 1, 2, 6, 3 | -6.200 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 10, n=19, 0, 2, 1, 4, 1 | -5.385 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 3, n=82, 4, 7, 10, 15, 7 | -1.930 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +23 days, n=21, 2, 4, 0, 4, 0 | -4.670 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 2, n=89, 0, 0, 2, 3, 2 | NA Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +5 days, n=26, 0, 2, 0, 5, 2 | -5.385 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +16 days, n=21, 0, 1, 0, 4, 1 | -2.950 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 4, n=84, 0, 0, 2, 2, 1 | NA Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 5, n=75, 5, 4, 8, 12, 5 | -3.705 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +9 days, n=27, 0, 1, 0, 3, 2 | -6.200 Log10 copies per milliliter |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 7, n=23, 1, 1, 1, 3, 1 | -6.200 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +2 days, n=32, 0, 1, 2, 6, 3 | -2.495 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +16 days, n=21, 0, 1, 0, 4, 1 | NA Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +23 days, n=21, 2, 4, 0, 4, 0 | NA Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 2, n=89, 0, 0, 2, 3, 2 | -3.750 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 3, n=82, 4, 7, 10, 15, 7 | -2.215 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 4, n=84, 0, 0, 2, 2, 1 | -4.895 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 5, n=75, 5, 4, 8, 12, 5 | -3.285 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 7, n=23, 1, 1, 1, 3, 1 | -3.030 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 10, n=19, 0, 2, 1, 4, 1 | -6.430 Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +5 days, n=26, 0, 2, 0, 5, 2 | NA Log10 copies per milliliter |
| Cohort 2: Children (1 to <2 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +9 days, n=27, 0, 1, 0, 3, 2 | NA Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 10, n=19, 0, 2, 1, 4, 1 | -4.760 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 4, n=84, 0, 0, 2, 2, 1 | -2.060 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 3, n=82, 4, 7, 10, 15, 7 | -1.330 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 2, n=89, 0, 0, 2, 3, 2 | -1.160 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +16 days, n=21, 0, 1, 0, 4, 1 | -3.825 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 7, n=23, 1, 1, 1, 3, 1 | -3.040 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +23 days, n=21, 2, 4, 0, 4, 0 | -3.825 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 5, n=75, 5, 4, 8, 12, 5 | -2.930 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +5 days, n=26, 0, 2, 0, 5, 2 | -4.190 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +2 days, n=32, 0, 1, 2, 6, 3 | -3.825 Log10 copies per milliliter |
| Cohort 3: Children (2 to <6 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +9 days, n=27, 0, 1, 0, 3, 2 | -4.190 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +2 days, n=32, 0, 1, 2, 6, 3 | -3.060 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 10, n=19, 0, 2, 1, 4, 1 | -1.670 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +5 days, n=26, 0, 2, 0, 5, 2 | -3.275 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 5, n=75, 5, 4, 8, 12, 5 | -2.550 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +23 days, n=21, 2, 4, 0, 4, 0 | NA Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +9 days, n=27, 0, 1, 0, 3, 2 | -3.865 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | PT +16 days, n=21, 0, 1, 0, 4, 1 | -4.610 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 7, n=23, 1, 1, 1, 3, 1 | -1.610 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 4, n=84, 0, 0, 2, 2, 1 | -2.550 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 3, n=82, 4, 7, 10, 15, 7 | -2.550 Log10 copies per milliliter |
| Cohort 4: Children (6 to <13 Years of Age) | Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points | Day 2, n=89, 0, 0, 2, 3, 2 | -2.280 Log10 copies per milliliter |
Secondary
Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays
The duration of hospitalization (H) reflects the number of hospitalization days between the date of the first dose of investigational product and the date of discharge. ICU stay includes total duration in ICU and may include days in ICU before entry into the study. For participants with a missing discharge date who were not discharged at the end of the study, the date of discharge was imputed to the last follow-up visit (post-treatment +23 days). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Time frame: Up to discharge from hospital
Population: ITT-E Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H, n=130, 7, 11, 12, 27, 14 | 15.0 Days |
| Cohort 6: Adults (18 Years and Older) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H-ICU, n=108, 4, 6, 8, 19, 9 | 11.50 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H, n=130, 7, 11, 12, 27, 14 | 7.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H-ICU, n=108, 4, 6, 8, 19, 9 | 7.5 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H, n=130, 7, 11, 12, 27, 14 | 4.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H-ICU, n=108, 4, 6, 8, 19, 9 | 5.0 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H, n=130, 7, 11, 12, 27, 14 | 6.5 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H-ICU, n=108, 4, 6, 8, 19, 9 | 5.5 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H, n=130, 7, 11, 12, 27, 14 | 6.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H-ICU, n=108, 4, 6, 8, 19, 9 | 8.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H, n=130, 7, 11, 12, 27, 14 | 6.5 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays | Duration of H-ICU, n=108, 4, 6, 8, 19, 9 | 8.0 Days |
Secondary
Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite)
Sustained resolution of the following vital signs (composite) was assessed: afebrile status, normal oxygen saturation, normal respiratory status, normal HR, and normal BP. Clinical response is defined as the resolution of at least four of five vital signs within the following resolution criteria, maintained for 24 hours or hospital discharge, whichever occurred first: Temperature in degrees Centigrade (\<=36.6 axilla, \<=37.2 oral, \<=37.7 rectal, core or tympanic); oxygen saturation (\>=95%, without supplemental oxygen); respiratory status (return to pre-morbid oxygen requirement, or no need for supplemental oxygen, or respiratory rate \<=60, \<=40, \<=34, \<=30, \<=24 or \<=24 breaths/minute without supplemental oxygen for Cohorts 1-6 respectively); HR (\<=160, \<=150, \<=140, \<=120, \<=100 or \<=100 bpm for Cohorts 1-6 respectively); SBP (\>=70, \>=74, \>=76, \>=80, \>=90 or \>=90 mmHg for Cohorts 1-6 respectively). Only those participants available at the specified time points were analyzed.
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | 9.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | 7.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | 3.5 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | 6.5 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | 4.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) | 5.0 Days |
Secondary
Median Time to Resolution of Individual Vital Signs
Times to return to afebrile status (normal body temperature), normal respiratory status, normal heart rate, and normal systolic blood pressure were assessed. Afebrile status is defined as a temperature \<=36.6 axilla, \<=37.2 oral, or \<=37.7 rectal, core or typanic, degrees Centigrade. A return to normal respiratory status is defined as either: (a) return to pre-morbid oxygen requirement; or (b) return to no need for supplemental oxygen; or (c) respiratory rate \<=60, \<=40, \<=34, \<=30, \<=24 or \<=24 breaths/minute (without supplemental oxygen) for Cohorts 1-6 respectively . A normal HR is defined as \<=160, \<=150, \<=140, \<=120, \<=100 or \<=100 bpm for Cohorts 1-6 respectively, and a normal SBP is defined as \>=70, \>=74, \>=76, \>=80, \>=90 or \>=90 mmHg for Cohorts 1-6 respectively. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles).
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Time to Resolution of Individual Vital Signs | SBP, n=128, 7, 11, 12, 27, 14 | 2.0 Days |
| Cohort 6: Adults (18 Years and Older) | Median Time to Resolution of Individual Vital Signs | Afebrile Status, n=120, 7, 11, 7, 24, 13 | 3.0 Days |
| Cohort 6: Adults (18 Years and Older) | Median Time to Resolution of Individual Vital Signs | Respiratory Status, n=89, 7, 10, 12, 23, 9 | 8.0 Days |
| Cohort 6: Adults (18 Years and Older) | Median Time to Resolution of Individual Vital Signs | HR, n=121, 7, 11, 12, 27, 13 | 2.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Resolution of Individual Vital Signs | Respiratory Status, n=89, 7, 10, 12, 23, 9 | 5.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Resolution of Individual Vital Signs | SBP, n=128, 7, 11, 12, 27, 14 | 2.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Resolution of Individual Vital Signs | Afebrile Status, n=120, 7, 11, 7, 24, 13 | 4.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Resolution of Individual Vital Signs | HR, n=121, 7, 11, 12, 27, 13 | 2.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Resolution of Individual Vital Signs | HR, n=121, 7, 11, 12, 27, 13 | 2.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Resolution of Individual Vital Signs | Afebrile Status, n=120, 7, 11, 7, 24, 13 | 2.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Resolution of Individual Vital Signs | SBP, n=128, 7, 11, 12, 27, 14 | 2.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Resolution of Individual Vital Signs | Respiratory Status, n=89, 7, 10, 12, 23, 9 | 2.0 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Resolution of Individual Vital Signs | HR, n=121, 7, 11, 12, 27, 13 | 2.0 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Resolution of Individual Vital Signs | Respiratory Status, n=89, 7, 10, 12, 23, 9 | 3.5 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Resolution of Individual Vital Signs | SBP, n=128, 7, 11, 12, 27, 14 | 2.0 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Resolution of Individual Vital Signs | Afebrile Status, n=120, 7, 11, 7, 24, 13 | 25.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Resolution of Individual Vital Signs | Afebrile Status, n=120, 7, 11, 7, 24, 13 | 3.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Resolution of Individual Vital Signs | SBP, n=128, 7, 11, 12, 27, 14 | 2.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Resolution of Individual Vital Signs | HR, n=121, 7, 11, 12, 27, 13 | 2.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Resolution of Individual Vital Signs | Respiratory Status, n=89, 7, 10, 12, 23, 9 | 3.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Resolution of Individual Vital Signs | Respiratory Status, n=89, 7, 10, 12, 23, 9 | 2.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Resolution of Individual Vital Signs | Afebrile Status, n=120, 7, 11, 7, 24, 13 | 3.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Resolution of Individual Vital Signs | SBP, n=128, 7, 11, 12, 27, 14 | 2.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Resolution of Individual Vital Signs | HR, n=121, 7, 11, 12, 27, 13 | 2.0 Days |
Secondary
Median Time to Return to Pre-morbid Functional Status
Time to return to pre-morbid functional status was assessed on a 3-point scale (bed rest, limited ambulation, or unrestricted). Only those participants available at the specified time points were analyzed.
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Time to Return to Pre-morbid Functional Status | 10.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Return to Pre-morbid Functional Status | 8.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Return to Pre-morbid Functional Status | 3.0 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Return to Pre-morbid Functional Status | 5.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Return to Pre-morbid Functional Status | 5.5 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Return to Pre-morbid Functional Status | 4.0 Days |
Secondary
Median Time to Virologic Improvement
Time to virologic improvement is defined as a 2-log drop in viral load or undetectable viral ribonucleic acid (RNA) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples (PCR positive at Baseline). Only those participants available at the specified time points were analyzed.
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population consisted of all participants who receiveed at least one dose of IV zanamivir.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Median Time to Virologic Improvement | 3.0 Days |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Median Time to Virologic Improvement | 4.0 Days |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Median Time to Virologic Improvement | 4.0 Days |
| Cohort 2: Children (1 to <2 Years of Age) | Median Time to Virologic Improvement | 3.0 Days |
| Cohort 3: Children (2 to <6 Years of Age) | Median Time to Virologic Improvement | 5.0 Days |
| Cohort 4: Children (6 to <13 Years of Age) | Median Time to Virologic Improvement | 4.0 Days |
Secondary
Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza
Concomitant medications (prescription and non-prescription) were permitted during the course of the study at the Investigator's discretion (except for prohibited medications: during the treatment period with IV zanamivir, other influenza antiviral drugs were not permitted). The number of participants who were treated with antibiotics for influenza complications was summarized.
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | 63 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | 5 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | 7 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | 7 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | 12 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza | 6 Participants |
Secondary
Number of Participants With Any AE Categorized as an Influenza Complication
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Any AE Categorized as an Influenza Complication | 45 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With Any AE Categorized as an Influenza Complication | 4 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With Any AE Categorized as an Influenza Complication | 4 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With Any AE Categorized as an Influenza Complication | 3 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With Any AE Categorized as an Influenza Complication | 8 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With Any AE Categorized as an Influenza Complication | 3 Participants |
Secondary
Number of Participants With the Indicated Mortality Status at Day 14 and Day 28
The number of participants who died on or before Study Day 14 and Study Day 28 was summarized. Only those participants available at the specified time points were analyzed.
Time frame: Day 14 and Day 28
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, No | 113 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, Yes | 17 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, No | 108 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, Yes | 22 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, No | 7 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, Yes | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, No | 7 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, Yes | 0 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, Yes | 1 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, No | 10 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, Yes | 0 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, No | 11 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, No | 12 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, Yes | 0 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, Yes | 0 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, No | 12 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, No | 26 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, Yes | 1 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, Yes | 1 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, No | 26 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, Yes | 2 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, No | 11 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 28, Yes | 3 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 | Died on or before Study Day 14, No | 12 Participants |
Secondary
Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation
Ventilation status was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Ventilation status was assessed once daily during inpatient follow-up visits. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD) at any time (AT) on study and at Baseline (Day 1) are summarized.
Time frame: Up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: ECMO | 4 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: Endotracheal | 74 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, SOD | 91 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: ECMO | 3 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: Endotracheal | 60 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, SOD | 46 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: Endotracheal | 3 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: ECMO | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, SOD | 1 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: ECMO | 0 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, SOD | 3 Participants |
| Cohorts 1-5: Pediatrics/Adolescents (6 Months to <18 Years) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: Endotracheal | 2 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, SOD | 3 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: Endotracheal | 3 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: ECMO | 1 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, SOD | 5 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: ECMO | 1 Participants |
| Cohort 1: Infants (6 Months to <1 Year of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: Endotracheal | 5 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: ECMO | 0 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: Endotracheal | 4 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, SOD | 7 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, SOD | 1 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: Endotracheal | 4 Participants |
| Cohort 2: Children (1 to <2 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: ECMO | 0 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: ECMO | 2 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: Endotracheal | 11 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: Endotracheal | 14 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, SOD | 13 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: ECMO | 2 Participants |
| Cohort 3: Children (2 to <6 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, SOD | 6 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: ECMO | 1 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, SOD | 5 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, Machine-Assisted: Endotracheal | 4 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | Day 1, SOD | 1 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: Endotracheal | 4 Participants |
| Cohort 4: Children (6 to <13 Years of Age) | Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation | AT on Study, Machine-Assisted: ECMO | 1 Participants |
Secondary
Number of Participants With Treatment-emergent (TE) Mutations
Viral RNA isolated from participants at Baseline (Day 1) and post-Baseline visits were sequenced to determine the presence of TE neuraminidase (NA) and hemagglutinin (HA) mutations resulting from selective pressure. A mutation was considered to be TE if it was not present at Baseline and was present in the last post-Baseline sample analyzed.These mutations were classified as either known to confer zanamvir resistance or novel mutations with unknown clinical significance. Please note: pediatric data are pending and will be updated when available.
Time frame: Baseline and up to post-treatment (PT) + 23 days
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Treatment-emergent (TE) Mutations | Known Zanamivir-Resistant NA Mutations | 0 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Treatment-emergent (TE) Mutations | Novel NA Mutations | 5 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Treatment-emergent (TE) Mutations | Resistant HA Mutations | 2 Participants |
| Cohort 6: Adults (18 Years and Older) | Number of Participants With Treatment-emergent (TE) Mutations | Novel HA Mutations | 4 Participants |