A Multicenter Study of the Safety of Oseltamivir Administered Intravenously for the Treatment of Influenza in Patients Aged Greater Than or Equal to 13 Years
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 118
- Primary Endpoint
- Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 13 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Oseltamivir IV (Drug)
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.
Intervention: Oseltamivir Oral (Drug)
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.
Intervention: Oseltamivir IV (Drug)
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.
Intervention: Oseltamivir Oral (Drug)
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.
Intervention: Oseltamivir IV (Drug)
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.
Intervention: Oseltamivir Oral (Drug)
Outcomes
Primary Outcomes
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death
Time Frame: Up to 30 days
Safety was assessed by adverse events (AEs) as measured by the collection of AEs, vital signs, electrocardiograms and laboratory parameters. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. On treatment = AEs that started between the day of first dose and within 2 days after the last dose. Off treatment = AEs that started more than 2 days after the last dose of study drug.
Secondary Outcomes
- Pharmacokinetics(Days 1, 3)
- Percentage of Participants With Viral Shedding by Culture or RT-PCR(Days 1, 4, 6, 11, 15 and 30)
- Percentage of Participants With Viral Shedding by Culture(Days 1, 4, 6, 11, 15, 30)
- Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)(Days 1, 4, 6, 11, 15 and 30)
- Change From Baseline in Influenza Titer by Culture at Day 4(Baseline, Day 4)
- Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4(Baseline, Day 4)
- Percentage of Participants Who Had a Fever During the Study(Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108)
- Time to Resolution of Fever for Participants Who Had a Fever at Baseline(Baseline, Up to 30 Days)
- Number of Participants With Viral Resistance(30 days)
- Percentage of Participants With Influenza Symptoms(Days 1, 11, 15, 30)