A Study of Intravenously Administered Tamiflu (Oseltamivir) in Patients Over 13 Years of Age With Influenza

• Pharmacokinetics [ Time Frame: Days 1, 3 ] [ Designated as safety issue: No ]
• Percentage of Participants With Viral Shedding by Culture or RT-PCR [ Time Frame: Days 1, 4, 6, 11, 15 and 30 ] [ Designated as safety issue: No ]
  Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by a positive culture [log10 median tissue culture infective dose (TCID50) > 0.5) or detection by RT-PCR (log 10 copies/mL).
• Percentage of Participants With Viral Shedding by Culture [ Time Frame: Days 1, 4, 6, 11, 15, 30 ] [ Designated as safety issue: No ]
  Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by a positive culture=log10 median tissue culture infective dose (TCID50) > 0.5.
• Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) [ Time Frame: Days 1, 4, 6, 11, 15 and 30 ] [ Designated as safety issue: No ]
  Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by detection by RT-PCR (log 10 copies/mL).
• Change From Baseline in Influenza Titer by Culture at Day 4 [ Time Frame: Baseline, Day 4 ] [ Designated as safety issue: No ]
  Nasal and throat swabs collected at Baseline and Day 4 were sent to a laboratory for analysis. Viral influenza titer (amount of virus present) was determined by culture. A log 10 median tissue culture infective dose (TCID50) > 0.5= Positive culture. A negative change from Baseline indicated improvement (less virus present).
• Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 [ Time Frame: Baseline, Day 4 ] [ Designated as safety issue: No ]
  Nasal and throat swabs were collected at Baseline and Day 4 and were sent to a central laboratory for analysis. Influenza Viral titers (amount of virus present) were determined by RT-PCR for Flu A and Flu B and were reported in log 10 copies/milliliter (mL). A negative change from Baseline indicated improvement (less virus present).
• Percentage of Participants Who Had a Fever During the Study [ Time Frame: Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108 ] [ Designated as safety issue: No ]
  Fever was defined as a temperature of ≥ 37.8 C (degrees Celcius).
• Time to Resolution of Fever for Participants Who Had a Fever at Baseline [ Time Frame: Baseline, Up to 30 Days ] [ Designated as safety issue: No ]
  Fever was defined as a temperature of ≥ 37.8 C (degrees Celsius). Resolution of fever was a temperature ≤ 37.2 for at least 21.5 hours.
• Number of Participants With Viral Resistance [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  Nasal and Throat swabs were collected on Days 1, 4, 6, 11, 15 and 30 and were sent to a central laboratory for testing. Viral resistance was determined by phenotypic and genotypic testing.
• Percentage of Participants With Influenza Symptoms [ Time Frame: Days 1, 11, 15, 30 ] [ Designated as safety issue: No ]
  Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.

• Pharmacokinetics [ Time Frame: Days 1, 3 ] [ Designated as safety issue: No ]
• Viral load and shedding [ Time Frame: Days 1, 4, 6, 11 ] [ Designated as safety issue: No ]

This partially randomized, multi-center parallel-group study will evaluate the safety, pharmacokinetics and the effect on viral load and viral shedding of Tamiflu (Oseltamivir) in patients with influenza. Adult and adolescent patients will be randomized to receive either 100 mg or 200 mg of study drug intravenously every 12 hours. Investigators and patients are blinded to knowledge of the assigned dose of Tamiflu. There is an option to convert to oral Tamiflu after 6 intravenous infusions. The anticipated time on study treatment is 5 days, with an optional treatment extension of a further 5 days, if necessary. There will be a non-randomized, open-label treatment group for patients with moderate/severe renal impairment or renal failure. Intravenous dose levels and frequency will be adjusted appropriately to their renal situation.

• Drug: Oseltamivir IV
  Oseltamivir IV infusions over 2 hours two times a day (every 12 hours) for 5 days for patients with moderate renal impairment. Patients with severe renal impairment received once daily dosing and patients on renal replacement therapy received dose/frequency according to protocol.
  Other Name: TAMIFLU®
• Drug: Oseltamivir Oral
  Oseltamivir (TAMIFLU®) capsules taken orally for 5 days. Twice daily (every 12 hours) for patients with moderate renal impairment, once daily for patients with severe renal impairment and dose frequency according to protocol for patients on renal replacement therapy.
  Other Name: TAMIFLU®

• Experimental: Oseltamivir (TAMIFLU®) 100 mg
  Oseltamivir (TAMIFLU®) 100 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 75 mg oral oseltamivir twice daily to complete the 5 days of treatment. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days.
  Interventions:

  • Drug: Oseltamivir IV
  • Drug: Oseltamivir Oral
• Experimental: Oseltamivir (TAMIFLU®) 200 mg
  Oseltamivir (TAMIFLU®) 200 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 150 mg oral oseltamivir twice daily for 5 days. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days.
  Interventions:

  • Drug: Oseltamivir IV
  • Drug: Oseltamivir Oral
• Experimental: Oseltamivir Open Label
  Moderate/Severe renal impaired participants received open label oseltamivir IV or oseltamivir capsules at reduced doses for 5 days as per protocol. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug as per protocol.
  Interventions:

  • Drug: Oseltamivir IV
  • Drug: Oseltamivir Oral

Inclusion Criteria:

• Adult and adolescent patients, 13 years of age and older
• Diagnosis of influenza
• ≤ 144 hours between the onset of influenza-like illness and first dose of study drug

Non-randomized, open-label treatment group:

• Patients with moderate/severe renal impairment or renal failure with creatinine clearance 10-60 mL/min

Exclusion Criteria:

• Clinical evidence of severe hepatic decompensation at the time of randomization
• Acute ischemia or significant arrhythmia