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

• To evaluate the safety and tolerability of peramivir administered intramuscularly. [ Time Frame: Through Day 14 ]
• To evaluate changes in influenza virus titer in nasopharyngeal samples (viral shedding) in response to treatment. [ Time Frame: Through Day 14 ]

• Subject's Severity of Illness (Score*Hours) [ Time Frame: Information collected predose on Day 1 and then once daily through Day 14 ]

  A subject's severity of illness (area under the symptom score curve, as measured in score-hours) was assessed using available symptom score data until the time of alleviation of symptoms.The score-hours were calculated as the product of the daily symptom score times the hours to alleviation. All available data until time of alleviation were utilized.

  The daily symptom score was defined as the sum of the 7 symptoms of influenza recorded by the subject in the diary each day (cough; sore throat; nasal congestion; myalgia [aches and pains]; headache; feverishness; and fatigue), each graded on a 4-point severity scale [0, absent; 1, mild; 2, moderate; 3, severe]); for the composite score, individual scores were summed, with a range from 0 to 21.

• Time to Resolution of Fever [ Time Frame: Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 ]
  Time to resolution of fever was defined as the number of hours from initiation of study drug until temperature was less than 37.2 °C (99.0 °F) and no antipyretic medication had been taken for at least 12 hours.
• Incidence of Influenza-related Complications [ Time Frame: 14 days ]
  Study personnel were provided with an IRC checklist in the CRF to evaluate the subject for the presence of clinical signs and/or symptoms of the following IRCs: sinusitis, otitis, bronchitis, and pneumonia. Subjects with clinical signs and/or symptoms consistent with these conditions at Screening were not eligible for enrollment in this study.
• Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) [ Time Frame: Baseline ]
  Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates.
• Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) [ Time Frame: Baseline and up to 14 days ]
  Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype.
• Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) [ Time Frame: Baseline and up to 14 days ]
  Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug.
• Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) [ Time Frame: Baseline and up to 14 days ]
  Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug.

• Drug: Peramivir
  600 mg peramivir administered as bilateral 2-mL intramuscular injection
• Drug: Placebo
  Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.

• Experimental: Peramivir 600 mg
  600 mg peramivir administered as bilateral 2-mL intramuscular injection.
  Intervention: Drug: Peramivir
• Placebo Comparator: Placebo
  Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.
  Intervention: Drug: Placebo

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.