Clinical Trial Results:
An open label, prospective, pharmacokinetic/pharmacodynamic and safety evaluation of oseltamivir (Tamiflu®) in the treatment of infants 0 to less than 12 months of age with confirmed influenza infection.
Summary
|
|
EudraCT number |
2009-014365-12 |
Trial protocol |
ES FR DE GB BE NL IT |
Global end of trial date |
04 Jun 2014
|
Results information
|
|
Results version number |
v1 |
This version publication date |
01 Apr 2016
|
First version publication date |
01 Apr 2016
|
Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
WP22849
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00988325 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH 4070
|
||
Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
|
||
Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000365-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
26 Jun 2012
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
02 Apr 2012
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
04 Jun 2014
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To define the pharmacokinetics of oseltamivir and oseltamivir carboxylate in children with confirmed influenza up to one year of age.
|
||
Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and ICH E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all participants and/or their legally authorized representative. Participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Jan 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 14
|
||
Country: Number of subjects enrolled |
Spain: 8
|
||
Country: Number of subjects enrolled |
France: 1
|
||
Country: Number of subjects enrolled |
Germany: 35
|
||
Country: Number of subjects enrolled |
Italy: 5
|
||
Country: Number of subjects enrolled |
Belgium: 2
|
||
Worldwide total number of subjects |
65
|
||
EEA total number of subjects |
65
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
5
|
||
Infants and toddlers (28 days-23 months) |
60
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
|||||||||||||
Recruitment
|
|||||||||||||
Recruitment details |
The study was conducted across 11 centers in Spain, Italy, France, Germany, Belgium, and Poland from 10 January 2011 to 04 April 2012. | ||||||||||||
Pre-assignment
|
|||||||||||||
Screening details |
A total of 65 participants were enrolled. | ||||||||||||
Period 1
|
|||||||||||||
Period 1 title |
Overall period
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Arms
|
|||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||
Arm title
|
Oseltamivir 3 mg | ||||||||||||
Arm description |
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 milligram/kilogram (mg/kg) twice a day for 5 days. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Oseltamivir
|
||||||||||||
Investigational medicinal product code |
Ro 64-0796
|
||||||||||||
Other name |
Tamiflu
|
||||||||||||
Pharmaceutical forms |
Oral suspension
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
The investigational medicinal product (IMP) was provided as 75 mg oseltamivir capsules; however, this was compounded to final concentration of the 10 milligram per milliliter (mg/mL) of oseltamivir in water. It was referred as a bottle of compounded suspension and was used while administering the prescribed dose.
|
||||||||||||
Arm title
|
Oseltamivir 2.5 mg | ||||||||||||
Arm description |
Participants aged 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Oseltamivir
|
||||||||||||
Investigational medicinal product code |
Ro 64-0796
|
||||||||||||
Other name |
Tamiflu
|
||||||||||||
Pharmaceutical forms |
Oral suspension
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
The investigational medicinal product (IMP) was provided as 75 mg oseltamivir capsules; however, this was compounded to final concentration of the 10 milligram per milliliter (mg/mL) of oseltamivir in water. It was referred as a bottle of compounded suspension and was used while administering the prescribed dose.
|
||||||||||||
Arm title
|
Oseltamivir 2 mg | ||||||||||||
Arm description |
Participants aged 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Oseltamivir
|
||||||||||||
Investigational medicinal product code |
Ro 64-0796
|
||||||||||||
Other name |
Tamiflu
|
||||||||||||
Pharmaceutical forms |
Oral suspension
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
The investigational medicinal product (IMP) was provided as 75 mg oseltamivir capsules; however, this was compounded to final concentration of the 10 milligram per milliliter (mg/mL) of oseltamivir in water. It was referred as a bottle of compounded suspension and was used while administering the prescribed dose.
|
||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir 3 mg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 milligram/kilogram (mg/kg) twice a day for 5 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir 2.5 mg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants aged 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir 2 mg
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants aged 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Oseltamivir 3 mg
|
||
Reporting group description |
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 milligram/kilogram (mg/kg) twice a day for 5 days. | ||
Reporting group title |
Oseltamivir 2.5 mg
|
||
Reporting group description |
Participants aged 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days. | ||
Reporting group title |
Oseltamivir 2 mg
|
||
Reporting group description |
Participants aged 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days. | ||
Subject analysis set title |
Pharmacokinetic population
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol.
|
||
Subject analysis set title |
Intent to treat infection (ITTI) population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
ITTI population consisted of all infants who had a positive PCR or viral culture at baseline or any time after first dose dministration and was same as pharmacodynamics (PD) population.
|
||
Subject analysis set title |
Safety population
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Safety population included all treated participants with at least one post-baseline safety assessment (vital sings like temperature, respiratory rate, blood pressure, pulse rate).
|
||
Subject analysis set title |
Reporting group: Genotype A (H1N1)pdm09
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Genotype A (H1N1)pdm09 was present in 21 participants of age group 91 to <365 days, 9 participants of age group 31 to 90 days, and 2 participants of age group less than or equal to (<=) 30 days.
|
||
Subject analysis set title |
Reporting group: Genotype A H3
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Genotype Type A H3 was present in 4 participants and 6 participants of age groups 91 to <365 days and 31 to 90 days, respectively.
|
||
Subject analysis set title |
Reporting group: Genotype B
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Genotype B was present in 12, 2, and 2 participants of age groups <365 days, 31 to 90 days, and <=30 days, respectively.
|
|
|||||||||||||||||||||||||
End point title |
Mean steady state area under plasma concentration time curve time zero to 12 hours of oseltamivir and oseltamivir carboxylate [1] | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is an active metabolite of oseltamivir. At steady state, area under curve from time zero to 12 hours (AUC0-12) was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule. This analysis was performed on PK population. As the EudraCT portal does not accept ‘not estimated’, we have presented an arbitrary value (99999999) for the same.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
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 performed for this end point. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [2] - Data is presented for the participants available at the time of assessment. [3] - Data is presented for the participants available at the time of assessment. [4] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean steady-state maximum observed plasma concentration of oseltamivir and oseltamivir carboxylate [5] | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is an active metabolite of oseltamivir. Maximum observed plasma concentration was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis. This analysis was performed on PK population.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
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 performed for this end point. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [6] - Data is presented for the participants available at the time of assessment. [7] - Data is presented for the participants available at the time of assessment. [8] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean steady-state minimum observed plasma concentration of oseltamivir and oseltamivir carboxylate [9] | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is active metabolite of oseltamivir. Minimum observed plasma concentration was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis. This analysis was performed on PK population.
|
||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
Notes [9] - 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 performed for this end point. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [10] - Data is presented for the participants available at the time of assessment. [11] - Data is presented for the participants available at the time of assessment. [12] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Median time to the maximum observed plasma concentration of oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is an active metabolite of oseltamivir. Time for required to attend maximum plasma concentration was estimated using non-compartmental methods. This analysis was performed on PK population.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [13] - Data is presented for the participants available at the time of assessment. [14] - Data is presented for the participants available at the time of assessment. [15] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean apparent elimination half life of oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
Elimination half life is defined as the time required for elimination of a drug to half its plasma concentration and was computed using non-compartmental method. This analysis was performed on PK population. As the EudraCT portal does not accept ‘not estimated’, we have presented an arbitrary value (99999999) for the same.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [16] - Data is presented for the participants available at the time of assessment. [17] - Data is presented for the participants available at the time of assessment. [18] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean apparent first-order elimination rate constant of oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is active metabolite of oseltamivir. The apparent first-order elimination rate constant was determined by linear regression analysis of terminal data points. A minimum of 3 data points were used for lambda Z estimation. By reporting tool convention, if n<3, no summary statistics were calculated. This analysis was performed on PK population. As the EudraCT portal does not accept ‘not estimated’, we have presented an arbitrary value (99999999) for the same.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [19] - Data is presented for the participants available at the time of assessment. [20] - Data is presented for the participants available at the time of assessment. [21] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean total plasma clearance as a function of bioavailability and apparent plasma clearance of the metabolite as a function of bioavailability of oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is an active metabolite of oseltamivir. Total plasma clearance as a function of bioavailability was calculated as dose/AUCinf, where AUCinf represents the area under the plasma concentration-time curve of the analyte over the time interval from zero extrapolated to infinity. This analysis was performed on PK population. As the EudraCT portal does not accept ‘not estimated’, we have presented an arbitrary value (99999999) for the same.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [22] - Data is presented for the participants available at the time of assessment. [23] - Data is presented for the participants available at the time of assessment. [24] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean volume of distribution as a function of bioavailability of oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is an active metabolite of oseltamivir. The volume of distribution as a function of bioavailability is defined as the theoretical volume in which the total amount of analyte would need to be uniformly distributed to produce the desired blood concentration of a drug. This analysis was performed on PK population. As the EudraCT portal does not accept ‘not estimated’, we have presented an arbitrary value (99999999) for the same.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [25] - Data is presented for the participants available at the time of assessment. [26] - Data is presented for the participants available at the time of assessment. [27] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean time of the last measurable plasma concentration for oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
Oseltamivir carboxylate is an active metabolite of oseltamivir. This analysis was performed on PK population.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of participants with change from Baseline in neurological assessment scores over time | ||||||||||||||||||||
End point description |
Neurological assessment was performed to assess the mental state of the participants through two scales: Infant face scale and Glasgow coma scale. Each scale consists of 3 sub-scales: eye opening (ranging 1 to 4), verbal response (ranging 1 to 5), and motor responses (ranging 1 to 6). The final score is the sum of these ranges and is scored between 3 and 15. Three being the worst, and 15 the best. Change from Baseline (Day 1) is change of final score post-baseline minus the final score at Baseline. The final score of the participants at Baseline was reported as 15. This analysis was performed on safety population.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) to Day 30
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Median time to cessation of viral shedding in participants with positive culture at Baseline | ||||||||||||||||||||
End point description |
Median time to cessation of viral shedding was calculated for all participants with positive by culture / by PCR at Baseline using all data points between the start of the treatment and the 1st time point of negative culture without subsequent positive culture results. These time-to-event analyses were only performed for the viral titre. The day when participants stopped shedding the virus and all the participants from respective groups showed negative viral culture on the corresponding days. This time point was equivalent to change from Baseline of 50% tissue culture infective dose [(log10TCID50)]. This analysis was performed using ITTI population.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) to Day 30
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with virus shedding by virus type over time | ||||||||||||||||||||||||||||||||||||
End point description |
The viral titer was measured by culture and reported in log10 (50% tissue culture infective dose [TCID50]). The viral load was analyzed by PCR and reported as log10 particles/mL. It analyzed the number of days required by observed number of participants to completely shed virus from their body reflecting change from Baseline in log10 (TCID50). This analysis was performed using ITTI population.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18, Day 30
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [28] - Data is presented for the participants available at the time of assessment. [29] - Data is presented for the participants available at the time of assessment. [30] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Median time to resolution of fever in participants with fever at the Baseline | ||||||||||||||||||||
End point description |
This was performed for all participants who had fever at Baseline. Fever is defined as body temperature > 37.0 degree Celsius. Rectal temperature is converted by subtracting 1 degree Celsius. Time to resolution of fever was defined as the time from the initiation of treatment to first time the afebrile state was reached and maintained for at least 21.5 hours, where afebrile state was defined as axillary temperature <= 37 degree Celsius. This analysis was performed on ITTI population.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From Baseline (Day 1) to Day 30
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [31] - Data is presented for the participants available at the time of assessment. [32] - Data is presented for the participants available at the time of assessment. [33] - Data is presented for the participants available at the time of assessment. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of participants with decline of body temperature to the afebrile state over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
This was performed for all participants who had fever at baseline Fever is defined as body temperature >37.0ºC. Rectal temperature is converted by subtracting 1 ºC. The rate of decline of body temperature was calculated as the slope of body temperature between the baseline temperature and the 1st temperature below 37°C. Participants with decline in body temperature were considered to have no fever; however, participants who did not show any decline in body temperature were considered to have persisting fever. This analysis was performed on ITTI population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18, Day 30
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [34] - Participants available at a particular time of assessment were included in the analysis. [35] - Participants available at a particular time of assessment were included in the analysis. [36] - Participants available at a particular time of assessment were included in the analysis. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of participants with adverse events, serious adverse events and secondary illness | ||||||||||||||||||||||||
End point description |
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. Secondary illnesses were influenza disease-related events, namely bronchitis, pneumonia, otitis media, and sinusitis that resolved without sequelae. This analysis was performed using safety population.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to Day 23
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Number of participants showing within-participant variability in vital signs | ||||||||||||||||
End point description |
Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and heart rate were examined for any consistent within-participant post-baseline changes and none were identified. Due to the small numbers of participants in a cohort and the extent of influenza induced variability, clinically significant changes in vital sign patterns cannot be detected. This analysis was performed on ITTI population.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Up to Day 30
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Mean last measurable plasma concentration of oseltamivir and oseltamivir carboxylate | ||||||||||||||||||||||||
End point description |
The last measurable plasma concentration of oseltamivir and oseltamivir carboxylate was the last quantifiable concentration of oseltamivir or oseltamivir carboxylate, respectively. This analysis was performed on PK population.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses were taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose was taken on Day 1
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 23 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Serious adverse events (SAEs) and other adverse events (AEs) were reported for the safety population. Safety population included all treated participants with at least one post-baseline safety assessment.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir 3 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir 2.5 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants aged 31 to 90 days received oral suspension of oseltamivir 2.5 mg/Kg twice a day for 5 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oseltamivir 2 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/Kg twice a day for 5 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
08 Sep 2009 |
a) Added a third cohort, changing the number of cohorts from two to three, such that the original second cohort (0 to < 3 months) was now Cohort II (1 to < 3 months) and Cohort III (0 to 30 days), allowing infants younger than 1 month to participate.
b) Allowed dosing to continue for a further 5 days (an additional 10 doses) if the specimen collected on Day 6 was positive for influenza or the participant had viral infection symptoms.
|
||
01 Oct 2009 |
Changed the dosing of oseltamivir such that younger infants received a lower dose of oseltamivir i.e. (2.5 mg/Kg for participants of 1 to < 3 months and 2 mg/Kg for participants of 0 to 30 days), instead of all infants receiving 3 mg/Kg. |
||
23 Oct 2009 |
Changed, at FDA request, study drug preparation such that oseltamivir dry powder was reconstituted to a suspension with a concentration of 11 mg/mL instead of 12 mg/mL. |
||
30 Nov 2009 |
a) For consistency, changed the grading of the intensity of AEs from a 3-point scale to a 4-point scale (mild, moderate, severe, and life threatening).
b) Cohorts were defined in terms of infant’s age in days instead of age in months.
|
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |