A Phase II, Multicenter, Randomized, Placebo -Controlled, Study To Evaluate The Efficacy and Safety Of Intramuscular Peramivir 600 mg In Subjects With Uncomplicated Acute Influenza

Study Overview
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Brief Summary
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The purpose of this study is to determine whether peramivir is safe and effective in the treatment of uncomplicated seasonal influenza.

Official Title
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A Phase II, Multicenter, Randomized, Placebo -Controlled, Study To Evaluate The Efficacy and Safety Of Intramuscular Peramivir 600 mg In Subjects With Uncomplicated Acute Influenza

Conditions
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Acute, Uncomplicated Human Influenza

Intervention / Treatment
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* Drug: Peramivir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant female subjects age ≥18 years. A positive Influenza A or B Rapid Antigen Test (RAT) performed with a commercially available test kit on an adequate anterior nasal specimen, in accordance with the manufacturer's instructions. A negative initial RAT should be repeated within one hour. Presence of fever at time of screening of ≥38.0 ºC (≥100.4 ºF) taken orally, or ≥38.5 ºC (≥101.2 ºF) taken rectally. A subject self-report of a history of fever or feverishness within the 24 hours prior to screening will also qualify for enrollment in the absence of documented fever at the time of screening. Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of at least moderate severity. Presence of at least one constitutional symptom (myalgia [aches and pains], headache, feverishness, or fatigue) of at least moderate severity. Onset of symptoms no more than 36 hours before presentation for screening. Written informed consent. Exclusion Criteria: Women who are pregnant or breast-feeding. Presence of clinically significant signs of acute respiratory distress History of severe chronic obstructive pulmonary disease (COPD) or severe persistent asthma. History of heart failure or angina requiring daily pharmacotherapy with symptoms consistent with New York Heart Association Class III or IV functional status within the past 12 months. Screening ECG which suggests acute ischemia or presence of medically significant dysrhythmia. History of chronic renal impairment requiring hemodialysis and/or known or suspected to have moderate or severe renal impairment (actual or estimated creatinine clearance <50 mL/min). Clinical evidence of worsening of any chronic medical condition (temporally associated with the onset of symptoms of influenza) which, in the investigator's opinion, indicates that such finding(s) could represent complications of influenza. Current clinical evidence, including clinical signs and/or symptoms consistent with otitis, bronchitis, sinusitis and/or pneumonia, or active bacterial infection at any body site that requires therapy with oral or systemic antibiotics. Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy which would include oral or systemic treatment with > 10 mg prednisone or equivalent on a daily basis within 30 days of screening. Currently receiving treatment for viral hepatitis B or viral hepatitis C. Presence of known HIV infection with a CD4 count <350 cell/mm3. Current therapy with oral warfarin or other systemic anticoagulant. Receipt of any doses of rimantadine, amantadine, zanamivir, or oseltamivir in the 7 days prior to screening. Immunized against influenza with live attenuated virus vaccine (FluMist®) in the previous 21 days. Immunized against influenza with inactivated virus vaccine within the previous 14 days. Receipt of any intramuscular injection with the previous 7 days. History of alcohol abuse or drug addiction within 1 year prior to admission in the study. Participation in a previous study of intramuscular or intravenous peramivir or previous participation in this study. Participation in a study of any investigational drug or device within the last 30 days.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peramivir 600 mg<br>600 mg peramivir administered as bilateral 2-mL intramuscular injection. | Drug: Peramivir<br>* 600 mg peramivir administered as bilateral 2-mL intramuscular injection<br>|
| Placebo Comparator: Placebo<br>Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection. | Drug: Placebo<br>* Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Alleviation of Symptoms (Kaplan-Meier Estimate) | The primary efficacy endpoint was the time to alleviation of symptoms calculated as the number of hours from initiation of study drug until the start of the time period in which all 7 symptoms of influenza were either absent or present at a level no greater than mild for at least 21.5 (24 hours - 10%) hours. Subjects with missing diary data were excluded and those who did not experience alleviation of symptoms were censored at the last observed symptom assessment. | Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Influenza Virus Shedding | Changes from Baseline in log10 TCID50/mL through Days 3, 4, and 9 were presented by treatment group for subjects with positive viral titers at Baseline (log10 TCID50/mL >0.5). | Baseline and Days 3, 4, 9 |