Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An Open-Label, Randomized, Adaptive, Two-Arm, Multicentre Trial to Evaluate Pharmacokinetics and Pharmacodynamics of Two Doses of Oseltamivir (TAMIFLU®) in the Treatment of Influenza in Immunocompromised Children Less Than 13 Years of Age, With Confirmed Influenza Infection

    Summary
    EudraCT number
    		 2012-002633-11
    Trial protocol
    		 ES   DE   FI   IT   PL   BE   GR  
    Global end of trial date
    07 Aug 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Feb 2019
    First version publication date
    16 Feb 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NV25719
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01715909
    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
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, globa.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Aug 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Aug 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Aug 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this trial was to generate data for the purpose of extrapolation of efficacy from adults with immunodeficiency and to compare and/or integrate exposure and response observations in the pediatric immunocompromised population to that seen in other, non-immunocompromised populations.
    Protection of trial subjects
    All study subjects, parents or guardians were required to read and sign an Informed Consent Form.
    Background therapy
    		 - Conditioning regimen prior to hematopoietic stem cell transplantation (HSCT) or less than 6 months after HSCT - Induction, consolidation, or re-intensification chemotherapy for a hematological malignancy (patients on maintenance therapy were excluded)
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Jan 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Colombia: 1
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Greece: 5
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Mexico: 1
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    Spain: 11
    Worldwide total number of subjects
    30
    EEA total number of subjects
    22
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    1
    Children (2-11 years)
    25
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Thirty subjects were enrolled over 5 northern hemisphere influenza seasons and 5 southern hemisphere influenza seasons at approximately 50 sites in order to enroll at least 20 subjects evaluable for the primary endpoint. The first subject was enrolled on 22 January 2014 and the last visit completed date for the last subject was on 17 July 2018.

    Pre-assignment
    Screening details
    		 Subjects with symptoms of less than 96 hours duration were screened by reverse transcriptase polymerase chain reaction (RT-PCR), culture, or rapid influenza diagnostic test (RIDT) for influenza infection prior to randomization. Influenza was confirmed by RT-PCR by the central laboratory.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Experimental: Conventional Dose
    Arm description
    		 Paediatric immunocompromised subjects less than 13 years of age received conventional dose of oseltamivir (30 to 75 milligrams [mg]) according to weight orally twice daily for a minimum of 5 days and a maximum of 20 days. Infants less than 1 year of age were to receive 3 mg/kg
    Arm type
    		 Experimental

    Investigational medicinal product name
    oseltamivir
    Investigational medicinal product code
    Other name
    Tamiflu
    Pharmaceutical forms
    Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Dose ranging between 30 to 75 milligrams (mg) based on body weight, administered orally as suspension or capsule twice daily for a minimum of 5 days and until a negative result for influenza by RT-PCR for a maximum of 20 days. Either the capsules or the oral suspension could be used as deemed appropriate by the investigator.

    Arm title
    		 Experimental: 3x Conventional Dose
    Arm description
    		 Paediatric immunocompromised subjects less than 13 years of age received 3x conventional dose of oseltamivir (90 to 225 milligrams [mg]) according to weight orally twice daily for a minimum of 5 days and a maximum of 20 days. Infants less than 1 year of age were to be assigned to the conventional group only.
    Arm type
    		 Experimental

    Investigational medicinal product name
    oseltamivir
    Investigational medicinal product code
    Other name
    Tamiflu
    Pharmaceutical forms
    Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Dose ranging between 90 to 225 milligrams (mg) based on body weight, administered orally as suspension or capsule twice daily for a minimum of 5 days and until a negative result for influenza by RT-PCR for a maximum of 20 days. Either the capsules or the oral suspension could be used as deemed appropriate by the investigator.

    Number of subjects in period 1
    		Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Started
    15
    15
    Completed
    14
    13
    Not completed
    1
    2
         Consent withdrawn by subject
    -
    2
         Non-compliance
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Experimental: Conventional Dose
    Reporting group description
    		 Paediatric immunocompromised subjects less than 13 years of age received conventional dose of oseltamivir (30 to 75 milligrams [mg]) according to weight orally twice daily for a minimum of 5 days and a maximum of 20 days. Infants less than 1 year of age were to receive 3 mg/kg

    Reporting group title
    Experimental: 3x Conventional Dose
    Reporting group description
    		 Paediatric immunocompromised subjects less than 13 years of age received 3x conventional dose of oseltamivir (90 to 225 milligrams [mg]) according to weight orally twice daily for a minimum of 5 days and a maximum of 20 days. Infants less than 1 year of age were to be assigned to the conventional group only.

    Reporting group values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose Total
    Number of subjects
    		 15 15 30
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 6.9 ± 4.2 4.3 ± 2.3 -
    Gender Categorical
    Units: Subjects
        Female
    		 5 4 9
        Male
    		 10 11 21

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Experimental: Conventional Dose
    Reporting group description
    		 Paediatric immunocompromised subjects less than 13 years of age received conventional dose of oseltamivir (30 to 75 milligrams [mg]) according to weight orally twice daily for a minimum of 5 days and a maximum of 20 days. Infants less than 1 year of age were to receive 3 mg/kg

    Reporting group title
    Experimental: 3x Conventional Dose
    Reporting group description
    		 Paediatric immunocompromised subjects less than 13 years of age received 3x conventional dose of oseltamivir (90 to 225 milligrams [mg]) according to weight orally twice daily for a minimum of 5 days and a maximum of 20 days. Infants less than 1 year of age were to be assigned to the conventional group only.

    Subject analysis set title
    Intent-to-Treat (ITT) Patient Population
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    All subjects who received at least one dose of oseltamivir regardless of whether they had any follow-up assessments. Subjects were grouped on the basis of randomized treatment. If there was any doubt whether a subject was treated, that subject was assumed to have been treated for the purposes of analysis.

    Subject analysis set title
    Intent-to-treat influenza-infected (ITTi) Subject Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    A subset of ITT subjects who had laboratory confirmed influenza infection from any swab sample collected at baseline or during the study (PCR or culture, not RIDT). The ITTi population is the primary efficacy analysis population unless specified otherwise. This excluded subjects who did not meet the definition of immunocompromised in the protocol. Subjects were grouped based on randomized treatment.

    Subject analysis set title
    Pharmacokinetic Evaluable (PKEP) Subject Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All patients in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit timepoint.

    Subject analysis set title
    Safety Evaluable Patient Population (SEP)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The same as the ITT population. Subjects were classified according to treatment actually received.

    Primary: Pharmacokinetics: Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir

    		 Close Top of page
    End point title
    		 Pharmacokinetics: Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir [1]
    End point description
    AUC0-12 was reported at steady state as nanograms per hour per millilitre (ng/mL*hr). Measured in the PKEP population.
    End point type
    Primary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours Post-dose on Days 3 or 4
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: ng/mL*hr
        arithmetic mean (standard deviation)
    265 ± 91.9
    568 ± 162
    No statistical analyses for this end point

    Primary: Pharmacokinetics: Steady State AUC0-12 of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Pharmacokinetics: Steady State AUC0-12 of Oseltamivir Carboxylate [2]
    End point description
    AUC0-12 was reported at steady state as nanograms per hour per millilitre (ng/mL*hr). The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Primary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4. 8 hours Post-dose on Days 3 or 4
    Notes
    [2] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: ng/mL*hr
        arithmetic mean (standard deviation)
    4350 ± 2320
    8210 ± 2500
    No statistical analyses for this end point

    Primary: Pharmacokinetics: Steady-state Maximum Plasma Concentration (Cmax) of Oseltamivir

    		 Close Top of page
    End point title
    		 Pharmacokinetics: Steady-state Maximum Plasma Concentration (Cmax) of Oseltamivir [3]
    End point description
    Cmax was reported as nanograms per millilitre (ng/mL). The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Primary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours Post-dose on Days 3 or 4
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    61.9 ± 19.5
    153 ± 49.8
    No statistical analyses for this end point

    Primary: Pharmacokinetics: Steady-state Cmax of Osltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Pharmacokinetics: Steady-state Cmax of Osltamivir Carboxylate [4]
    End point description
    Cmax was reported as nanograms per millilitre (ng/mL). The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Primary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours Post-dose on Days 3 or 4
    Notes
    [4] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    434 ± 211
    852 ± 288
    No statistical analyses for this end point

    Primary: Pharmacokinetics: Trough Plasma Concentration (Ctrough) of Oseltamivir

    		 Close Top of page
    End point title
    		 Pharmacokinetics: Trough Plasma Concentration (Ctrough) of Oseltamivir [5]
    End point description
    Ctrough was reported as nanograms per millilitre (ng/mL). The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Primary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    5.17 ± 2.43
    9.07 ± 3.08
    No statistical analyses for this end point

    Primary: Pharmacokinetics: Ctrough of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Pharmacokinetics: Ctrough of Oseltamivir Carboxylate [6]
    End point description
    Ctrough was reported as nanograms per millilitre (ng/mL). The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Primary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration) on Days 3 or 4
    Notes
    [6] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    276 ± 173
    486 ± 136
    No statistical analyses for this end point

    Primary: Time to Cessation of Viral Shedding, as Assessed by Culture Testing

    		 Close Top of page
    End point title
    		 Time to Cessation of Viral Shedding, as Assessed by Culture Testing [7]
    End point description
    Viral titer was determined from nasal swabs. It was reported in log10 scale and expressed in 50% tissue culture infectious dose (TCID50) obtained after viral culture followed by hemagglutination assay for H1N1 and Flu B strains or viral nucleoprotein (NP) ELISA for H3N2 strains. Time to cessation of viral shedding was summarized by the median of the Kaplan-Meier curve for each of the two dose regimens and associated 95% CIs.The ITTi population was used in the analysis.
    End point type
    Primary
    End point timeframe
    From randomization to negative culture test result (up to Day 50)
    Notes
    [7] - 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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    11
    9
    Units: hours
        median (confidence interval 95%)
    109.2 (60.9 to 153.0)
    75.9 (54.7 to 344.1)
    No statistical analyses for this end point

    Primary: Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR)

    		 Close Top of page
    End point title
    		 Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) [8]
    End point description
    Viral load was determined from nasal swabs. It was reported in log10 scale and expressed in virus particles per millilitre (vp/mL) calculated from the quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Time to cessation of viral shedding was summarized by the median of the Kaplan-Meier curve for each of the two dose regimens and associated 95% CIs. The ITTi population was used in the analysis.
    End point type
    Primary
    End point timeframe
    From randomization to negative PCR test result (up to Day 50)
    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: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    11
    9
    Units: hours
        median (confidence interval 95%)
    157.2 (125.3 to 658.0)
    242.3 (60.4 to 392.1)
    No statistical analyses for this end point

    Secondary: Time to Resolution (TTR) of Influenza Symptoms (including fever)

    		 Close Top of page
    End point title
    		 Time to Resolution (TTR) of Influenza Symptoms (including fever)
    End point description
    TTR of all influenza symptoms was defined as the time in hours from randomization to the start of the 24 hour period in which all 18 symptoms items (Canadian Acute Respiratory Infections Scale [CARIFS] 18-symptom scale) had scores of </= 1 (minor problem) and remained </= 1 for at least 21.5 hours. Reported are TTRs in the ITTi population. 9999=not estimable
    End point type
    Secondary
    End point timeframe
    From randomization to resolution of all influenza symptoms (up to Day 50)
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    11
    9
    Units: hours
        median (confidence interval 95%)
    179.4 (24.7 to 9999)
    34.5 (0.0 to 84.9)
    No statistical analyses for this end point

    Secondary: Number of Participants With Adverse Events

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events
    End point description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. The safety population included all subjects who received at least one dose of study drug and had a safety assessment performed post randomisation.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 50
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    15
    15
    Units: number of subjects
    number (not applicable)
        Adverse Events
    96
    77
        Serious Adverse Events
    11
    7
    No statistical analyses for this end point

    Secondary: Number of Subjects With Influenza Associated Complications

    		 Close Top of page
    End point title
    		 Number of Subjects With Influenza Associated Complications
    End point description
    Influenza associated complications include secondary bacterial infections (e.g. bronchitis, sinusitis, pneumonia and otitis media), length of hospital stay and intensive care unit (ICU) admissions, frequency of O2 use and time on ventilator. Reported is the number of subjects with at least one event in the ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 50
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    15
    15
    Units: Number of Subjects
    number (not applicable)
        Number of subjects with secondary infections
    0
    2
        Number of subjects hospitalized
    10
    7
        Number of subjects requiring O2 use
    2
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Viral Resistance

    		 Close Top of page
    End point title
    		 Number of Subjects With Viral Resistance
    End point description
    Viral resistance was determined from nasal swabs. Genotypic and phenotypic viral resistance were investigated. Susceptibility of the virus to inhibition by oseltamivir was determined with the NA-Star assay using the cell culture supernatants of samples from which infectious viruses could be detected by titration after culture (baseline and last titration positive sample). The IC50 (concentration of drug required to inhibit the viral neuraminidase activity by 50%) of each sample was determined together with the reference IC50 value using the appropriate reference virus (A/Puerto Rico/8/34 for influenza A viruses, B/Lee/40 for influenza B viruses) run in parallel. The IC50 values were expressed in units of nanomoles per liter (nM/l). Reported is the number of subjects who developed viral resistance in the ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 50
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    11
    9
    Units: Number
    number (not applicable)
        Overall Resistance
    1
    2
    No statistical analyses for this end point

    Secondary: Half-life (t1/2) of Oseltamivir

    		 Close Top of page
    End point title
    		 Half-life (t1/2) of Oseltamivir
    End point description
    Elimination half-life (t1/2) was reported as hours. The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: hour
        arithmetic mean (standard deviation)
    1.97 ± 0.245
    1.83 ± 0.117
    No statistical analyses for this end point

    Secondary: t1/2 of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 t1/2 of Oseltamivir Carboxylate
    End point description
    Elimination half-life (t1/2) was reported as hours. The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: hour
        arithmetic mean (standard deviation)
    0.189 ± 0.153
    0.0881 ± 0.0417
    No statistical analyses for this end point

    Secondary: Time to Maximum Concentration (Tmax) of Oseltamivir

    		 Close Top of page
    End point title
    		 Time to Maximum Concentration (Tmax) of Oseltamivir
    End point description
    Time to maximum concentration (tmax) was reported as hours. The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: hour
        arithmetic mean (standard deviation)
    1.41 ± 0.56
    1.25 ± 0.354
    No statistical analyses for this end point

    Secondary: Tmax of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Tmax of Oseltamivir Carboxylate
    End point description
    Time to maximum concentration (tmax) was reported as hours. The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Experimental: Conventional Dose Experimental: 3x Conventional Dose
    Number of subjects analysed
    14
    12
    Units: hour
        arithmetic mean (standard deviation)
    4.18 ± 1.05
    3.83 ± 0.634
    No statistical analyses for this end point

    Secondary: Elimination Rate Constant (Ke) of Oseltamivir

    		 Close Top of page
    End point title
    		 Elimination Rate Constant (Ke) of Oseltamivir
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    26
    Units: 1/hour
        arithmetic mean (standard deviation)
    6.43 ± 1.96
    No statistical analyses for this end point

    Secondary: Ke of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Ke of Oseltamivir Carboxylate
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    26
    Units: 1/hour
        arithmetic mean (standard deviation)
    8.2 ± 5.63
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (V/F) of Oseltamivir

    		 Close Top of page
    End point title
    		 Apparent Volume of Distribution (V/F) of Oseltamivir
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    26
    Units: litre (L)
        arithmetic mean (standard deviation)
    35.8 ± 10.7
    No statistical analyses for this end point

    Secondary: V/F of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 V/F of Oseltamivir Carboxylate
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    26
    Units: litre
        arithmetic mean (standard deviation)
    2.67 ± 1.75
    No statistical analyses for this end point

    Secondary: Apparent Clearance (CL/F) of Oseltamivir

    		 Close Top of page
    End point title
    		 Apparent Clearance (CL/F) of Oseltamivir
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    26
    Units: litre per hour (L/hr)
        arithmetic mean (standard deviation)
    228 ± 97.3
    No statistical analyses for this end point

    Secondary: CL/F of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 CL/F of Oseltamivir Carboxylate
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    26
    Units: L/hr
        arithmetic mean (standard deviation)
    14.9 ± 5.3
    No statistical analyses for this end point

    Secondary: Time to Last Measurable Concentration (Tlast) of Oseltamivir

    		 Close Top of page
    End point title
    		 Time to Last Measurable Concentration (Tlast) of Oseltamivir
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    0 [9]
    Units: hour
        arithmetic mean (standard deviation)
    ±
    Notes
    [9] - Data was not analysed for this end point
    No statistical analyses for this end point

    Secondary: Tlast of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Tlast of Oseltamivir Carboxylate
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    0 [10]
    Units: hour
        arithmetic mean (standard deviation)
    ±
    Notes
    [10] - Data was not analysed for this end point
    No statistical analyses for this end point

    Secondary: Last Measurable Concentration (Clast) of Oseltamivir

    		 Close Top of page
    End point title
    		 Last Measurable Concentration (Clast) of Oseltamivir
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    0 [11]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ±
    Notes
    [11] - Data was not analysed for this end point
    No statistical analyses for this end point

    Secondary: Clast of Oseltamivir Carboxylate

    		 Close Top of page
    End point title
    		 Clast of Oseltamivir Carboxylate
    End point description
    The PKEP population comprised all subjects in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit time point.
    End point type
    Secondary
    End point timeframe
    Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4
    End point values
    		 Pharmacokinetic Evaluable (PKEP) Subject Population
    Number of subjects analysed
    0 [12]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ±
    Notes
    [12] - Data was not analysed for this end point
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to Day 50
    Adverse event reporting additional description
    The safety population included all subjects who received at least one treatment with study medication.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Experimental: Triple Standard Dose
    Reporting group description
    		 Immunocompromised participants will receive triple standard dose (90 to 225 mg) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for </= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.

    Reporting group title
    Experimental: Standard Dose
    Reporting group description
    		 Immunocompromised paticipants will receive standard dose (30 to 75 milligrams [mg]) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for </= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.

    Serious adverse events
    		 Experimental: Triple Standard Dose Experimental: Standard Dose
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 15 (33.33%)
    7 / 15 (46.67%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Body Temperature Increased
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile Neutropenia
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Graft Versus Host Disease
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Erythema of Eyelid
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eyelid Oedema
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoventilation
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device Malfunction
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Experimental: Triple Standard Dose Experimental: Standard Dose
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 15 (86.67%)
    12 / 15 (80.00%)
    Vascular disorders
    Thrombophlebitis Superficial
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    Platelet Transfusion
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    2
    4
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Chills
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Mucosal Inflammation
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Pyrexia
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         occurrences all number
    1
    2
    Immune system disorders
    Graft Versus Host Disease in Skin
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         occurrences all number
    1
    3
    Epistaxis
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Dyspnoea
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Respiratory Distress
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Psychiatric disorders
    Abnormal Behaviour
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Nervousness
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Blood Lactate Dehydrogenase Increased
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Body Temperature Increased
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    C-Reactive Protein Increased
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Escherichia Test Positive
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Transfusion Reaction
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Headache
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Tremor
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 15 (6.67%)
    4 / 15 (26.67%)
         occurrences all number
    3
    6
    Febrile Neutropenia
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         occurrences all number
    1
    1
    Leukopenia
         subjects affected / exposed
    2 / 15 (13.33%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    Neutropenia
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 15 (13.33%)
    2 / 15 (13.33%)
         occurrences all number
    3
    5
    Ear and labyrinth disorders
    Ear Pain
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Retinal Haemorrhage
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    2 / 15 (13.33%)
    2 / 15 (13.33%)
         occurrences all number
    8
    2
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Anal Inflammation
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    3 / 15 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    Diarrhoea
         subjects affected / exposed
    2 / 15 (13.33%)
    5 / 15 (33.33%)
         occurrences all number
    2
    5
    Dyschezia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Intestinal Pseudo-obstruction
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Lip Swelling
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    3 / 15 (20.00%)
    1 / 15 (6.67%)
         occurrences all number
    3
    1
    Parotid Gland Enlargement
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    6 / 15 (40.00%)
    5 / 15 (33.33%)
         occurrences all number
    8
    5
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 15 (13.33%)
    3 / 15 (20.00%)
         occurrences all number
    2
    3
    Rash Erythematous
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Skin Discolouration
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Glycosuria
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Renal Impairment
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Back Pain
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Neck Pain
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Pain in Extremity
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Cellulitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Citrobacter Infection
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Eye Infection
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    2
    Gastroenteritis
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Gastroenteritis Clostridial
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Herpes Virus Infection
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Septic Shock
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Viral Infection
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Vulvovaginitis
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Hypokalaemia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Hypomagnesaemia
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         occurrences all number
    1
    2
    Hypoproteinaemia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jul 2013
    In Protocol Version 2, the following significant changes were made: 1) The middle dose cohort (2x conventional oseltamivir dose) was discontinued with a concomitant increase in the size of the remaining two dose cohorts from 7 patients to 10 patients. This enriched the PK and PD data collected from the conventional and 3x conventional dose cohort and balanced the density of data collected for the doses tested compared to having more doses tested but with a lower data density per dose. 2) The age of the study population was restricted to patients aged 2 weeks to less than 13 years of age (as opposed to 0 − 18 years of age previously), which intended to enrich the dataset by allowing the data collected to be spread over a narrower age range. 3) Inclusion criteria referring to females in the reproductive age group were removed. 4) Study enrollment was modified to require at least 12 patients with onset of influenza symptoms less than < 48 hours prior to randomization. 5) Objectives were rephrased in order to clarify the purpose of the study. 6) Schedule of Assessments were amended to add a serum biochemistry sample requirement at baseline and on the PK sampling day (if serum creatinine results for these timepoints were not otherwise available) to allow estimation of creatinine clearance required for the population PK modeling.
    23 Jun 2014
    In Protocol Version 3, the following significant changes were made: 1) Study population was modified to remove the restriction that infants had to be 2 weeks of age. 2) An additional follow-up visit (Follow-Up Visit 2 occurring at least 30 days after the end of study treatment) was added. 3) Creatinine clearance estimates were corrected to include normalization for height, in line with the 2009 Schwartz formula. 4) Dose modification for infants (<1 year of age) with renal impairment was removed.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 08:46:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA