Safety, PK and Effectiveness of IV Peramivir Versus Oseltamivir in Pediatric Subjects With Uncomplicated Influenza

Safety evaluation included assessment of Adverse Events (AEs).

Time frame: 14 days

Population: The Safety population included all randomized subjects who received ≥ 1 partial dose of peramivir or oseltamivir.

Change in influenza viral titers was defined as the time-weighted change from Baseline in log\_10 tissue culture infective dose\_50 (TCID50/mL) and was summarized for each treatment group.

Time frame: Change from baseline assessed on days 3, 7 and 14.

Population: The Intent To Treat Infected (ITTI) population included all subjects who were enrolled, received study drug, and had confirmed influenza A and/or B by PCR. Thirteen subjects were excluded due to a negative or missing baseline titer.

The investigator performed a full physical exam at baseline. At each follow-up visit, study personnel evaluated the subject for the presence of clinical signs and symptoms of the following influenza-related complications: sinusitis, otitis media, bronchitis, and pneumonia requiring antibiotic use, diagnosed after initiation of treatment.

Time frame: 14 days

Population: Intent-to-treat infected (ITTI) population

Up to 4 blood samples will be drawn, where possible: immediately following infusion and 30 to 60 mins, 1 to 3 hrs and 4 to 6 hrs post-infusions. AUC calculations were performed in Phoenix WinNonlin using the linear/log trapezoidal rule. AUC0-last was calculated between start of the infusion and the time of the last measurable concentration.

Time frame: up to 6 hours post peramivir infusion

Population: The Intent-to-Treat (ITTI) population included all randomized subjects. Of these 114 subjects, 106 had sufficient PK samples collected for inclusion in the peramivir PK analysis

Assessment of viral shedding in bilateral, mid-nasal swab specimens taken at baseline and then on Day 3, 7 and 14.

Time frame: 14 days

Population: Intent to treat infected (ITTI) population + ITT population with positive baseline influenza viral titers \[\> 0.5 log10 TCID50/mL\]; a total of 84 subjects.

Time for fever resolution based on subject diary record of temperature recorded twice daily. A subject had resolution of fever if he/she had oral temperature of \< 99.4°F or an axillary temperature of \< 98.4°F and no antipyretic medications were taken for ≥ 12 hours. The time to resolution of fever was estimated for each age group and overall using the Kaplan-Meier method with temperature and symptom relief medication information obtained from the Subject Diary data.

Time frame: 14 days

Population: Intent to treat infected (ITTI) population. Subjects who did not have resolution of fever were censored at the time of their last non-missing post-baseline temperature assessment; this included 1 subject in the '≥ 28 days - \< 2 years' cohort treated with Peramivir. Seventeen subjects were excluded from summaries due to missing data or events resolving prior to initiation of study drug.

Subjects or parents or caregivers were asked to provide an assessment of age-appropriate influenza symptoms on a 4-point severity scale (0,absent; 1, mild; 2, moderate; 3, severe) twice daily beginning before screening on Day 1 until symptoms resolved or until the last follow-up visit. Time to alleviation of symptoms was the number of hours from initiation of study drug until the start of the time period in which all age-appropriate symptoms of influenza were either absent or present at a level no greater than mild for at least 21.5 (24 - 10%) hours. Subjects who did not experience alleviation of symptoms were censored at the last observed symptom assessment.

Time frame: 14 days

Population: Intent to treat infected (ITTI) population. Subjects with no alleviation of symptoms were censored at date of last post-baseline assessment; including 1 subject in the '≥ 28 days to \< 2 yrs, Peramivir' group, 1 subject in the '≥ 2 to \< 7 yrs, Peramivir' group, 4 subjects in the '≥ 7 to \< 13 yrs, Peramivir' group and 1 subject each in the '≥ 13 to \< 18 yrs' Peramivir and Oseltamivir groups. Seven subjects were excluded due to missing data or events resolving prior to initiation of study drug.