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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01050257
First received: January 14, 2010
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Influenza
Drug: Oseltamivir IV
Drug: Oseltamivir Oral
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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.


Enrollment: 118
Study Start Date: January 2010
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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®) 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.
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 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.
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®

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050257

  Show 96 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01050257     History of Changes
Other Study ID Numbers: NV25118
Study First Received: January 14, 2010
Results First Received: August 28, 2013
Last Updated: August 28, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014