A Study of Oseltamivir (Tamiflu) for Treatment of Influenza in Immunocompromised Participants.

Resistance was defined as the presence of oseltamivir resistance mutations in viruses isolated from nasopharyngeal swab samples, identified by sequencing of the neuraminidase (NA) and hemagglutinin (HA) genes (genotypic resistance) and/or determination of the oseltamivir concentration at which the response is reduced by half (IC50) in an NA inhibition assay (phenotypic resistance). Reported are post-baseline phenotypic and genotypic resistance in adults \>/= 18 years and children and adolescents \<18 years in the modified Intent-to-Treat infected (mITTi) population.

Time frame: Baseline up to Day 40

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

An adverse event is any untoward medical occurrence in a participant 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.

Time frame: Baseline up to Day 40

Population: The safety population included all participants who received at least one dose of study drug and had a safety assessment performed post randomization.

The percentage of transplant patients in the safety population who experienced tissue rejection and/or GvHD is reported.

Time frame: Baseline up to Day 40

Population: The safety population included all participants who received at least one dose of study drug and had a safety assessment performed post randomization.

Nasopharyngeal swab samples were cultured in Madin-Darby Canine Kidney cells. Culture supernatants were harvested after 2 weeks, or after a full-blown cytopathic effect was observed. Presence of infectious viruses in the cell culture supernatants (viral titer), expressed as log10 50% Tissue Culture Infectious Dose/milliliter (TCID50/mL), was determined by hemagglutination assay using turkey erythrocytes for H1 and B viruses or by detection of the virus nucleoprotein (NP) using ELISA for H3 viruses. A value of \< 0.5 log10 TCID50/mL was interpreted as negative. Data are reported for adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Nasopharyngeal swab samples were tested for influenza A and B RNA using semi-quantitative RT-PCR specific for influenza A and B matrix gene, respectively, after viral RNA isolation. Cycle threshold (Ct) value was determined for each sample. Conversion of Ct values into viral load, expressed as log10 virus particles/mL (vp/mL), was obtained using external standard curves ran in parallel in all RT-PCR experiments. A value of \< 2.6 log10 vp/mL for Flu A strains and \< 3.0 log10 vp/mL for Flu B strains was interpreted as a negative result. Data are reported for adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Reported is the duration of hospitalization at any time between treatment initiation and the end of the study period, in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline up to Day 40

Population: The ITTi population included all participants randomized and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Reported is the percentage of participants, who required hospitalization at any time between treatment initiation and the end of the study period, in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline up to Day 40

Population: The ITTi population included all participants randomized and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Secondary illness included bronchitis, pneumonia, acute sinusitis, sinusitis, lower respiratory infection or otitis media. Reported is the percentage of participants with at least one event in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline up to Day 40

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Secondary illness included bronchitis, pneumonia, acute sinusitis, sinusitis, lower respiratory infection or otitis media. Reported is the percentage of participants with secondary illness, who initiated antibiotic treatment, in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline up to Day 40

Population: The safety population included all participants who received at least one dose of study drug and had a safety assessment performed post randomization.

Persistent shedding was defined as a viral load reduction \<1 log10 vp/mL at end of treatment compared with baseline. Reported is the percentage of participants with persistent viral shedding at end of treatment in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline to Day 11 (EOT)

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Viral shedding was determined through measurement of the viral titer after viral culture in Madin-Darby Canine Kidney cells by hemagglutination assay (for Flu A/H1N1 and Flu B) and NP-ELISA (for Flu A/H3N2) and expressed in log10 TCID50/mL. Reported is the percentage of participants with viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Viral shedding was determined by direct viral load measurement from nasopharyngeal swabs by RT-PCR assay and expressed in log10 vp/mL. Reported is the percentage of subjects with viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline (Day 1), Day 2/3, Day 6, Day 8, Day 11 end of treatment (EOT), follow-up (FU) Day 15 and FU Day 40.

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Reported here are oseltamivir carboxylate CL/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate CL/F data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir CL/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir CL/F data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate Vc/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate Vc/F data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir Vc/F data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir Vc/F data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

AUC0-12 was reported at steady state as nanograms per hour per milliliter. (ng\*hr/mL). Reported here are oseltamivir AUC0-12 data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

AUC0-12 will be reported at steady state as ng\*hr/mL. Reported here are oseltamivir carboxylate AUC0-12 data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate AUC0-12 data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all particiants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

AUC0-12 will be reported at steady state as ng\*hr/mL. Reported here are oseltamivir AUC0-12 data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all subjects in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate Cmax data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate Cmax data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir Cmax data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate Ctrough data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate Ctrough data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir Ctrough data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate ke data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oxeltamivir carboxylate ke data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir ke data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir ke data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir Cmax data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The pharmacokinetic evaluable patient (PKEP) population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir tmax data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate tmax data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir carboxylate tmax data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir data for adolescents and children \< 18 years. Individual data are provided as participants received different drug doses. Drug dose is indicated in the row title for each participant.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Reported here are oseltamivir Ctrough data for adults \>/= 18 years.

Time frame: Pre-dose (30 minutes), 1.5, 4, 8 hours postdose on Day 6 or any day after the 11th dose

Population: The PKEP population comprised all participants in the ITT population who had at least one valid post-dose drug concentration measurement at a scheduled visit time point.

Viral shedding was determined through measurement of the viral titer after viral culture in Madin-Darby Canine Kidney cells by hemagglutination assay (for Flu A/H1N1 and Flu B) and NP-ELISA (for Flu A/H3N2) and expressed in log10 TCID50/mL. Reported is the time to cessation of viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline up to Day 40

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Viral shedding was determined by direct viral load measurement from nasopharyngeal swabs by RT-PCR assay and expressed in log10 vp/mL. Reported is the time to cessation of viral shedding over time in adults \>/= 18 years and adolescents and children \< 18 years.

Time frame: Baseline up to Day 40

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

Fever was defined as temperature \>/= 37.8 degrees Celsius at any time point during the study. TTR of fever was determined in Adults \>/= 18 years, Adults and adolescents \>/= 13 years and Children \< 13 years of the mITTi population.

Time frame: Baseline up to Day 40

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.

TTR of all clinical influenza symptoms was defined as the time from treatment initiation to the start of the 24-hour period in which all 7 influenza symptoms had scores \</= 1 (mild) and remained \</=1 for at least 21.5 hours. . Reported are TTRs in adults \>/= 18 years, adults and adolescents \>/= 13 years and children \<13 years in the mITTi population.

Time frame: Baseline up to Day 40

Population: mITTi: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline, and for whom data were available.

The overall extent and severity of illness was quantified by the AUE of the total symptom scores over the duration of illness, i.e., from the start of treatment to the time symptoms first alleviated. Total symptom scores were calculated from the sum of seven individual symptom scores with each individual symptom scored from 0 (healthy) to 3 (worst sickness) and a maximum total symptom score of 21. The AUE of these average scores was then calculated for each participant using the trapezoidal rule (the trapezoidal rule calculates the area under any curve by adding up all trapezoids under such a curve). A larger area indicates more severe disease. In this study participants were treated for 10 days. If a participant had scored 21 on every visit then AUE would have been 21 score x 10 days x 24 hours/day =5040 score x hours units, which is the highest possible score. The lowest possible score is 0. Reported are results for adults \>/= 18 years in the mITTi population.

Time frame: Baseline up to Day 40

Population: mITTi population: all participants randomized to a particular treatment, regardless of whether they received that treatment or not, who received at least one dose of study drug and with central laboratory confirmation of influenza infection, excluding participants infected with oseltamivir-resistant influenza at baseline.