Clinical Trial Results:
An Open Label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir (Tamiflu®) in the Treatment of Children 1 to 12 Years of Age With Influenza Infection
Summary
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EudraCT number |
2016-003004-31 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
13 Dec 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Feb 2017
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First version publication date |
23 Feb 2017
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NP25139
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01033734 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Mar 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Dec 2012
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
This study was a prospective, open label, pharmacokinetic (PK)/pharmacodynamic (PD) and safety evaluation of intravenous (IV) oseltamivir therapy in three cohorts of children with influenza infection aged 6-12 years (Cohort I), 3-5 years (Cohort II) and 1-2 years (Cohort III). Children with symptoms of influenza were considered for enrollment into this study.
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Protection of trial subjects |
The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice according to the regulations and procedures described in the protocol.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Dec 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
1
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Children (2-11 years) |
7
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
Pre-assignment
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Screening details |
A total of 2836 participants were prescreened, of which 2828 failed evaluation. The most common reasons for screen failure included: negative influenza diagnosis, not meeting the age criterion, ability to tolerate/absorb oral medication, and an inability to comply with the study procedures. | ||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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Oseltamivir - overall | ||||||||||
Arm description |
Participants received oseltamivir (Tamiflu) twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight less than or equal to (<=) 23 kilograms (kg) received 3 milligrams per kilogram (mg/kg); participants with body weight more than (>) 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 milligrams (mg). For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Oseltamivir
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Investigational medicinal product code |
RO0640796
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Other name |
Tamiflu®
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Pharmaceutical forms |
Powder for oral suspension, Powder for solution for infusion
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Routes of administration |
Intravenous use, Oral use
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Dosage and administration details |
Participants received oseltamivir twice daily. The oseltamivir doses were based on participant’s age.
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Baseline characteristics reporting groups
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Reporting group title |
Oseltamivir - overall
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Reporting group description |
Participants received oseltamivir (Tamiflu) twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight less than or equal to (<=) 23 kilograms (kg) received 3 milligrams per kilogram (mg/kg); participants with body weight more than (>) 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 milligrams (mg). For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Oseltamivir - overall
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Reporting group description |
Participants received oseltamivir (Tamiflu) twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight less than or equal to (<=) 23 kilograms (kg) received 3 milligrams per kilogram (mg/kg); participants with body weight more than (>) 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 milligrams (mg). For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | ||
Subject analysis set title |
Oseltamivir: 6 to 12 Years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants aged 6 to 12 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
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Subject analysis set title |
Oseltamivir: 3 to 5 Years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants aged 3 to 5 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
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Subject analysis set title |
Oseltamivir: 1 to 2 Years
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants aged 1 to 2 Years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
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End point title |
Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1 [1] | ||||||||||||||||||||||||
End point description |
PK population included all treated participants who had at least one blood sample evaluable for drug concentration level. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [2] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 [3] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [4] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 [5] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [6] - No participant was evaluable for this arm. [7] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 [8] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [9] - No participant was evaluable for this arm. [10] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 [11] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [12] - No participant was evaluable for this arm. [13] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1 [14] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion
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Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [15] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2 [16] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [17] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 3 [18] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [19] - No participant was evaluable for this arm. [20] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4 [21] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [22] - No participant was evaluable for this arm. [23] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 5 [24] | ||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome. Here, 99999 represent data not estimable due to single participant analyzed.
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End point type |
Primary
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End point timeframe |
Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this open-label study. |
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Notes [25] - No participant was evaluable for this arm. [26] - No participant was evaluable for this arm. |
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No statistical analyses for this end point |
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End point title |
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories. Here, 9999 represent data not available as no participant was evaluable at specified time-point and 99999 represent data not estimable due to single participant analyzed.
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End point type |
Secondary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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No statistical analyses for this end point |
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End point title |
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories. Here, 9999 represent data not available as no participant was evaluable at specified time-point and 99999 represent data not estimable due to single participant analyzed.
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End point type |
Secondary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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No statistical analyses for this end point |
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End point title |
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories. Here, 9999 represent data not available as no participant was evaluable at specified time-point and 99999 represent data not estimable due to single participant analyzed.
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End point type |
Secondary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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No statistical analyses for this end point |
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End point title |
Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [27] - Data not available as no participant was evaluable for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [28] - Data not available as no participant was evaluable for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
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Notes [29] - Data not collected because of changes in planned analysis, due to early study termination. |
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No statistical analyses for this end point |
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End point title |
Participants With Greater Than or Equal to (>=) 5−Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values | ||||||||||||||||||||||||||||||
End point description |
IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either >=5 times change in the NAI IC50 visit value from the Reference value at a visit, >=5 times change in the NAI IC50 Visit value from the Baseline value. Safety population included all participants who received at least one dose of IV study medication and had a safety assessment performed after initiation of treatment. Here, number of participants analyzed = participants evaluable for this outcome measure, and n = participants evaluable for specified time-point, for each arm, respectively. Here, 9999 represent data not available as no participant was evaluable at specified time-point.
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End point type |
Secondary
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End point timeframe |
Baseline, Days 1, 6 and 30
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 30 days
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
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Reporting groups
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Reporting group title |
Oseltamivir - overall
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Reporting group description |
Participants received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight >23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir: 6 to 12 Years
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Reporting group description |
Participants aged 6 to 12 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir: 3 to 5 Years
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Reporting group description |
Participants aged 3 to 5 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir: 1 to 2 Years
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Reporting group description |
Participants aged 1 to 2 Years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant’s body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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08 Mar 2010 |
• Provided additional information regarding oseltamivir central nervous system (CNS) distribution
• Modified the requirements of IV therapy for a specified number of days and provided clarification on dosing for participants on continuous renal replacement therapy
• Removed optional blood pressure monitoring in children <5 years of age and clarified the study population and excluded medication
• Provided an updated schedule with amended timepoints
• Reduced the maximum concentration of IV oseltamivir to 1 milligrams per milliliter (mg/mL)
• Specified that adverse events (AEs) were to be graded based on the Division of Acquired Immune Deficiency Syndrome (AIDS) table for grading the severity of adult and pediatric AEs |
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13 May 2010 |
• Updated the synopsis to reflect changes in the protocol text
• Corrected the exposure data
• Modified dosing in participants with moderate renal impairment
• Revised Exclusion Criterion 1 to accommodate participants with moderate renal impairment
• Specified in the PD assessments section that, for participants who were discharged prior to Study Day 6, it was preferred that the participant returned to the clinic to have the swabs collected on the mornings of Study Day 3 or 4 since PK sampling could occur on Study Day 3 or 4 depending on the time of day (am or pm) initial dose was administered
• Corrected the pH value listed for the reconstituted solution of Tamiflu
• Increased the flexibility of PK sampling by specifying in the PK assessments section that sample collection (1) could occur on a day other than Study Day 1 due to operational logistics, and (2) could occur on Study Day 3 or 4 depending on the time of day (am or pm) that the initial dose was administered
• Added dosing recommendation for participants with renal impairment |
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19 Sep 2011 |
• Added results from nonclinical studies in juvenile animals
• Added clinical experience with the IV formulation text based on results from the previously ongoing adult multiple-dose Study NP25140
• Updated the exposure margins based on data from the multiple-dose IV Study NP25140
• Clarified the day of treatment completion depending on when dosing was started and whether one or two doses were received on Study Day 1
• Changed the upper limit of the range for moderate renal impairment from 50 milliliters per minute (mL/min) to 60 mL/min to reflect the most recent Food and Drug Administration (FDA) Guidance
• Revised the screening and eligibility text to allow flexibility to include data obtained from standard-of-care procedures prior to obtaining informed consent for study participation
• Revised to allow flexibility in PK sampling and clarification regarding blood collection |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
Low number of participants enrolled in the study at the time that the study was terminated limits conclusions that can be derived from the study data. |