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

Influenza Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01050257
• Other study ID #: NV25118
• Status: Completed
• Phase: Phase 3
• First received: January 14, 2010
• Last updated: August 28, 2013
• Start date: January 2010
• Est. completion date: September 2012

Study information

• Verified date: August 2013
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Denmark,  France,  Hungary,  Italy,  Lithuania,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death	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.	Up to 30 days	No
Secondary	Pharmacokinetics		Days 1, 3	No
Secondary	Percentage of Participants With Viral Shedding by Culture or RT-PCR	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).	Days 1, 4, 6, 11, 15 and 30	No
Secondary	Percentage of Participants With Viral Shedding by Culture	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.	Days 1, 4, 6, 11, 15, 30	No
Secondary	Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)	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).	Days 1, 4, 6, 11, 15 and 30	No
Secondary	Change From Baseline in Influenza Titer by Culture at Day 4	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).	Baseline, Day 4	No
Secondary	Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4	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).	Baseline, Day 4	No
Secondary	Percentage of Participants Who Had a Fever During the Study	Fever was defined as a temperature of = 37.8 C (degrees Celcius).	Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108	No
Secondary	Time to Resolution of Fever for Participants Who Had a Fever at Baseline	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.	Baseline, Up to 30 Days	No
Secondary	Number of Participants With Viral Resistance	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.	30 days	No
Secondary	Percentage of Participants With Influenza Symptoms	Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.	Days 1, 11, 15, 30	No