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Trial record 67 of 118 for:    oseltamivir

A Pharmacokinetic/Pharmacodynamic (PK/PD) and Safety Evaluation of Oseltamivir [Tamiflu] in the Treatment of Infants 0 to <12 Months of Age With Confirmed Flu Infection

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ClinicalTrials.gov Identifier: NCT00988325
Recruitment Status : Completed
First Posted : October 2, 2009
Results First Posted : March 20, 2017
Last Update Posted : March 20, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Influenza
Intervention Drug: Tamiflu
Enrollment 65
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. A total of 65 participants were screened.
Pre-assignment Details  
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description Participants aged 91 to <365 days received oral suspension of oseltamivir 3 milligram (mg)/kilogram (kg) twice a day for 5 days Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days.
Period Title: Overall Study
Started 40 20 5
Completed 40 20 5
Not Completed 0 0 0
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg Total
Hide Arm/Group Description Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days. Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days Total of all reporting groups
Overall Number of Baseline Participants 40 20 5 65
Hide Baseline Analysis Population 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).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 40 participants 20 participants 5 participants 65 participants
223.2  (79.41) 57.0  (17.24) 25.2  (5.36) 156.8  (105.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 20 participants 5 participants 65 participants
Female
19
  47.5%
8
  40.0%
2
  40.0%
29
  44.6%
Male
21
  52.5%
12
  60.0%
3
  60.0%
36
  55.4%
1.Primary Outcome
Title Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days.
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour (h)*nanogram(ng)/milliliter (mL)
Oseltamivir, n=37, 17, 4
277
(36.2%)
194
(47.8%)
142
(48.8%)
Oseltamivir carboxylate, n=18,11, 2
4990
(27.4%)
4920
(35.3%)
NA [1] 
(NA%)
[1]
Geometric Mean and Geometric Coefficient of Variation were not calculated for 2 participants analyzed. Individual data are not reported due to privacy concerns
2.Primary Outcome
Title Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is an active metabolite of oseltamivir. Cmax was estimated for both oseltamivir and Oseltamivir carboxylate by non-compartmental analysis.
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Oseltamivir
80.8
(47%)
62.5
(69.1%)
25.2
(211.6%)
Oseltamivir carboxylate
464
(37.7%)
530
(33.1%)
501
(22.2%)
3.Primary Outcome
Title Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is active metabolite of oseltamivir. Cmin was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration.
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days.
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Oseltamivir
2.88
(65.4%)
2.09
(52.6%)
2.56
(90.0%)
Oseltamivir carboxylate
238
(43.8%)
248
(51.5%)
169
(96.4%)
4.Secondary Outcome
Title Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is an active metabolite of oseltamivir.Tmax was estimated using non-compartmental methods
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Median (Full Range)
Unit of Measure: hours
Oseltamivir
1.08
(0.88 to 3.08)
1.08
(0.00 to 2.92)
1.08
(1.00 to 3.00)
Oseltamivir carboxylate
5.04
(2.08 to 7.00)
2.88
(0.00 to 6.67)
5.83
(2.58 to 6.67)
5.Secondary Outcome
Title Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate
Hide 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
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Oseltamivir, n= 37, 17, 4
2.02
(38.5%)
2.01
(49.3%)
1.66
(41.5%)
Oseltamivir carboxylate, n=18, 11, 2
9.45
(53.3%)
11.3
(92.7%)
NA [1] 
(NA%)
[1]
Geometric Mean and Geometric Coefficient of Variation were not calculated for 2 participants analyzed. Individual data are not reported due to privacy concerns
6.Secondary Outcome
Title Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is active metabolite of oseltamivir.The apparent first-order elimination rate constant (Lambda Z) 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
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days.
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 1/hour
Oseltamivir, n= 33, 11, 4
0.349
(39.9%)
0.338
(52.9%)
0.418
(41.5%)
Oseltamivir carboxylate, n=17, 7, 2
0.0735
(55.2%)
0.0475
(110.6%)
NA [1] 
(NA%)
[1]
Geometric Mean and Geometric Coefficient of Variation were not calculated for 2 participants analyzed. Individual data are not reported due to privacy concerns
7.Secondary Outcome
Title Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is active metabolite of oseltamivir. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days.
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Mean (Standard Deviation)
Unit of Measure: mL/hour
Oseltamivir, n= 37, 17, 4 80500  (42.8) 63000  (63.7) 50600  (39.9)
Oseltamivir carboxylate, n=18,11, 2 3940  (38.8) 2180  (54.86) NA [1]   (NA)
[1]
Total Plasma Clearance was not calculated for 2 participants analyzed. Individual data are not reported due to privacy concerns
8.Secondary Outcome
Title The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is active metabolite of oseltamivir. V/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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. n = participants with evaluable drug concentration.
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL
Oseltamivir, n= 37, 17, 4
234000
(66.2%)
183000
(87.9%)
121000
(69.8%)
Oseltamivir carboxylate, n=18,11, 2
53700
(78.1%)
35400
(96.5%)
NA [1] 
(NA%)
[1]
Geometric Mean and Geometric Coefficient of Variation were not calculated for 2 participants analyzed. Individual data are not reported due to privacy concerns
9.Secondary Outcome
Title Clast of Oseltamivir and Oseltamivir Carboxylate
Hide Description The last measurable plasma concentration of oseltamivir and oseltamivir carboxylate was the last quantifiable concentration of oseltamivir or oseltamivir carboxylate, respectively.
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all treated patients with at least one blood sample evaluable for drug concentration level and who were adhered to the protocol
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Oseltamivir
262
(39.2%)
176
(58.3%)
84.3
(154.4%)
Oseltamivir carboxylate
3800
(50.1%)
4410
(34.0%)
3940
(28.2%)
10.Secondary Outcome
Title Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate
Hide Description Oseltamivir carboxylate is an active metabolite of oseltamivir.
Time Frame 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses 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 taken on Day 1
Hide Outcome Measure Data
Hide Analysis Population 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.
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Oseltamivir
9.23
(30.1%)
8.53
(32.9%)
6.94
(24.2%)
Oseltamivir carboxylate
10.11
(21.2%)
10.64
(5.4%)
10.45
(5.3%)
11.Secondary Outcome
Title Number of Participants With Change From Baseline in Neurological Assessment Scores
Hide 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 subscales: 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. 3 being the worst, and 15 the best. Change from baseline is change of final score post-baseline minus the final score at baseline.
Time Frame Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all treated participants with at least one post-baseline safety assessment
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Measure Type: Number
Unit of Measure: participants
With change in infant face scale measurement score 0 2 0
With change in Glasgow coma scale assessment score 0 1 0
12.Secondary Outcome
Title Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline
Hide Description Median time to cessation of viral shedding was calculated for all patients with positive by culture / by polymerase chain reaction (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.
Time Frame Days 1, 3 or 4, 6, 11, 18, and 30
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days.
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Median (95% Confidence Interval)
Unit of Measure: hours
228.5
(118.0 to 231.0)
113.0
(63.0 to 230.0)
113.0
(110.0 to 116.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamivir 3 mg/kg, Oseltamivir 2.5 mg/kg, Oseltamivir 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.166
Comments p-value is for the comparison of the age cohorts (treatment groups)
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon Test was used for testing homogeneity of survival curves
Method of Estimation Estimation Parameter Median time to cessation of viral sheddi
Estimated Value 119
Confidence Interval (2-Sided) 95%
113 to 230
Estimation Comments Median time was estimated from the Kaplan-Meier curve (unstratified)
13.Secondary Outcome
Title Number of Participants With Virus Shedding by Virus Type
Hide 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. The number of patients positive for viral shedding by virus sub-type was measured on specified days from baseline to last visit on Day 30.
Time Frame Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
Arm/Group Title Type A (H1N1)pdm09 Type A H3 Type B
Hide Arm/Group 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 <=30 days
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
Genotype B was present in 12, 2, and 2 participants of age groups <365 days, 31 to 90 days, and <=30 days, respectively.
Overall Number of Participants Analyzed 32 10 16
Measure Type: Number
Unit of Measure: Participants
Baseline 32 10 14
Day 3 or 4 20 5 14
Day 6 12 4 7
Day 11 32 9 16
Day 18 +-2 0 1 0
Day 30 +-2 0 0 0
14.Secondary Outcome
Title Time to Resolution of Fever in Participants With Fever at the Baseline
Hide 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.
Time Frame Days 1 to 11; Day 18; Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 37 17 4
Median (Full Range)
Unit of Measure: hours
12.0
(9.0 to 17.0)
20.5
(12.0 to 36.0)
24.0
(14.0 to 43.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oseltamivir 3 mg/kg, Oseltamivir 2.5 mg/kg, Oseltamivir 2 mg/kg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.059
Comments The p-value is for the comparison of the age cohorts (not including Total)
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Time to Resolution of Fever in Patients
Estimated Value 14.5
Confidence Interval (2-Sided) 95%
12 to 20
Estimation Comments Median time was estimated from the Kaplan-Meier curve (unstratified)
15.Secondary Outcome
Title Percentage of Participants With Decline of Body Temperature to the Afebrile State
Hide 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.
Time Frame Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days.
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 33 11 4
Measure Type: Number
Unit of Measure: percentage of participants
Baseline, n=33, 11, 4, decline 36 55 25
Baseline, n=33, 11, 4, no decline 64 45 75
Day 4, n=33, 11, 4, decline 94 91 100
Day 4, n=33, 11, 4, no decline 6 9 0
Day 11, n=33, 11, 4, decline 97 100 100
Day 11, n=33, 11, 4, no decline 3 0 0
Day 18, n=16, 5, 1, decline 94 100 100
Day 18, n=16, 5, 1, no decline 6 0 0
Day 30, n=31, 9, 4, decline 97 89 100
Day 30, n=31, 9, 4, no decline 3 11 0
16.Secondary Outcome
Title Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness
Hide Description An Adverse Event (AEs) 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. An 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. Adverse events, serious adverse events, and secondary illness are reported for on-treatment period (from the first dose of oseltamivir upto 3 days after the last dose of oseltamivir [Approximately 14 days].
Time Frame Up to 3 days after the last dose of oseltamivir (Approximately 14 days)
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Hide Analysis Population Description
Safety population included all treated participants with at least one post-baseline safety assessment
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 40 20 5
Measure Type: Number
Unit of Measure: Participants
Participants with any AE 13 12 2
Participants with any SAE 3 1 0
Participants with secondary illness 0 1 0
17.Secondary Outcome
Title Number of Participants Showing Within-patient Variability in Vital Signs
Hide Description Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and heart rate were examined for any consistent within-patient post-baseline changes.
Time Frame Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days
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Hide Analysis Population Description
Safety population included all treated participants with at least one post-baseline safety assessment. Due to the small numbers of participants and the extent of influenza induced variability, changes in vital sign patterns cannot be detected.
Arm/Group Title Oseltamivir 3 mg/kg Oseltamivir 2.5 mg/kg Oseltamivir 2 mg/kg
Hide Arm/Group Description:
Participants aged 91 to <365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days
Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days
Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Up to 3 days after the last dose of oseltamivir (Approximately 14 days)
Adverse Event Reporting Description SAEs and other AEs were collected in the safety population. Safety population included all treated participants with at least one post-baseline safety assessment. All AEs are reported for on-treatment period (from the first dose of oseltamivir up to 3 days after the last dose of oseltamivir [Approximately 14 days].
 
Arm/Group Title Oseltamivir 3 mg Oseltamivir 2.5 mg Oseltamivir 2 mg
Hide Arm/Group Description Participants aged 91 to <365 days received oral suspension of oseltamivir 3 milligram (mg)/kilogram (kg) twice a day for 5 days Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/ twice a day for 5 days Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days
All-Cause Mortality
Oseltamivir 3 mg Oseltamivir 2.5 mg Oseltamivir 2 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Oseltamivir 3 mg Oseltamivir 2.5 mg Oseltamivir 2 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/40 (7.50%)   1/20 (5.00%)   0/5 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  1/40 (2.50%)  0/20 (0.00%)  0/5 (0.00%) 
Infections and infestations       
Respiratory syncytial virus bronchiolitis  1  1/40 (2.50%)  1/20 (5.00%)  0/5 (0.00%) 
Cellulitis orbital  1  1/40 (2.50%)  0/20 (0.00%)  0/5 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oseltamivir 3 mg Oseltamivir 2.5 mg Oseltamivir 2 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/40 (32.50%)   12/20 (60.00%)   2/5 (40.00%) 
Eye disorders       
Conjunctivitis  1  2/40 (5.00%)  0/20 (0.00%)  1/5 (20.00%) 
Gastrointestinal disorders       
Vomiting  1  10/40 (25.00%)  11/20 (55.00%)  0/5 (0.00%) 
Diarrhoea  1  4/40 (10.00%)  1/20 (5.00%)  0/5 (0.00%) 
Regurgitation  1  1/40 (2.50%)  6/20 (30.00%)  2/5 (40.00%) 
General disorders       
Pyrexia  1  3/40 (7.50%)  0/20 (0.00%)  0/5 (0.00%) 
Irritability  1  0/40 (0.00%)  2/20 (10.00%)  0/5 (0.00%) 
Crepitations  1  0/40 (0.00%)  1/20 (5.00%)  0/5 (0.00%) 
Infections and infestations       
Oral candidiasis  1  0/40 (0.00%)  1/20 (5.00%)  1/5 (20.00%) 
Rotavirus infection  1  1/40 (2.50%)  1/20 (5.00%)  0/5 (0.00%) 
Otitis media  1  0/40 (0.00%)  1/20 (5.00%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/40 (0.00%)  1/20 (5.00%)  0/5 (0.00%) 
Tachypnoea  1  0/40 (0.00%)  1/20 (5.00%)  0/5 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis diaper  1  0/40 (0.00%)  0/20 (0.00%)  1/5 (20.00%) 
Rash maculo−papular  1  0/40 (0.00%)  1/20 (5.00%)  0/5 (0.00%) 
Seborrhoeic dermatitis  1  0/40 (0.00%)  1/20 (5.00%)  0/5 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 616878333
EMail: global.trial_information@roche.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00988325     History of Changes
Other Study ID Numbers: WP22849
2009-014365-12
First Submitted: September 30, 2009
First Posted: October 2, 2009
Results First Submitted: February 18, 2016
Results First Posted: March 20, 2017
Last Update Posted: March 20, 2017