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

Study Overview
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Brief Summary
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This study will evaluate the safety, pharmacokinetics and effectiveness of a single dose of IV peramivir compared to a standard 5 day course of oral oseltamivir in the treatment of pediatric subjects with acute uncomplicated influenza.

Official Title
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A Phase 3, Randomized, Open Label, Active-controlled Study to Evaluate the Safety, Pharmacokinetics and Effectiveness of IV Peramivir Compared to Oral Oseltamivir in Pediatric Subjects With Acute Uncomplicated Influenza

Conditions
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Influenza

Intervention / Treatment
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* Drug: Peramivir
* Drug: Oseltamivir


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical signs and symptoms consistent with acute influenza infection consisting of an oral temperature ≥ 100°F (37.8°C) or rectal temperature ≥ 101.3ºF (≥ 38.5ºC) with at least one respiratory symptom (cough or rhinitis) OR Positive influenza determined by PCR or Rapid Antigen Test Onset of symptoms no more than 72 hours before presentation for screening for subjects < 2 years old. Key Exclusion Criteria: Pregnant or breast-feeding females Development of symptoms while hospitalized Presence of a chronic disease or illness that may indicate increased risk for influenza-related complications Presence of immunocompromised status

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peramivir (IV)<br>Subjects randomized to peramivir will receive an age appropriate single dose, diluted to a maximum volume of 100 mL in normal saline, administered as a short intravenous infusion over a minimum of 15 minutes. Subjects ≥12 years will receive a dose of 600 mg. Subjects <12 years will receive a dose of 12 mg/kg (to a maximum dose of 600 mg). Subjects < 6 months will receive a dose of 8 mg/kg. | Drug: Peramivir<br> <br> |
| Active Comparator: Oseltamivir<br>Subjects randomized to oral oseltamivir will receive an age appropriate dose twice daily for 5 days. Subjects ≥ 13 years will receive a 75mg dose administered as a capsule or oral suspension (twice daily for 5 days). Subjects < 13 years of age will receive a weight-based dose administered as a capsule or oral suspension (twice daily for 5 days). | Drug: Oseltamivir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability, as Measured by the Number of Participants Experiencing Adverse Events. | Safety evaluation included assessment of Adverse Events (AEs). | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Exposure of IV Peramivir as Measured by the Drug Concentration Over 6 Hours Post-dose | 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. | up to 6 hours post peramivir infusion | 
| Time to Resolution of Fever | 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. | 14 days | 
| Time to Resolution of Influenza Symptoms | 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. | 14 days | 
| Time to Reduction in Viral Shedding | Assessment of viral shedding in bilateral, mid-nasal swab specimens taken at baseline and then on Day 3, 7 and 14. | 14 days | 
| Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. | 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. | Change from baseline assessed on days 3, 7 and 14. | 
| Influenza-Related Complications Assessment. | 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. | 14 days |