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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00705406
First received: June 24, 2008
Last updated: February 12, 2015
Last verified: February 2015
  Purpose

The purpose of this study is to determine whether peramivir is safe and effective in the treatment of uncomplicated seasonal influenza.


Condition Intervention Phase
Acute, Uncomplicated Human Influenza
Drug: Peramivir
Drug: Placebo
Phase 2

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 Phase II, Multicenter, Randomized, Placebo -Controlled, Study To Evaluate The Efficacy and Safety Of Intramuscular Peramivir 600 mg In Subjects With Uncomplicated Acute Influenza

Resource links provided by NLM:


Further study details as provided by BioCryst Pharmaceuticals:

Primary Outcome Measures:
  • Time to Alleviation of Symptoms (Kaplan-Meier Estimate) [ Time Frame: Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 ] [ Designated as safety issue: No ]
    The primary efficacy endpoint was the time to alleviation of symptoms calculated as the number of hours from initiation of study drug until the start of the time period in which all 7 symptoms of influenza were either absent or present at a level no greater than mild for at least 21.5 (24 hours - 10%) hours. Subjects with missing diary data were excluded and those who did not experience alleviation of symptoms were censored at the last observed symptom assessment.


Secondary Outcome Measures:
  • Change in Influenza Virus Shedding [ Time Frame: Baseline and Days 3, 4, 9 ] [ Designated as safety issue: No ]
    Changes from Baseline in log10 TCID50/mL through Days 3, 4, and 9 were presented by treatment group for subjects with positive viral titers at Baseline (log10 TCID50/mL >0.5).


Other Outcome Measures:
  • Subject's Severity of Illness (Score*Hours) [ Time Frame: Information collected predose on Day 1 and then once daily through Day 14 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 405
Study Start Date: July 2008
Study Completion Date: October 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peramivir 600 mg
600 mg peramivir administered as bilateral 2-mL intramuscular injection.
Drug: Peramivir
600 mg peramivir administered as bilateral 2-mL intramuscular injection
Placebo Comparator: Placebo
Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.
Drug: Placebo
Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00705406

  Show 123 Study Locations
Sponsors and Collaborators
BioCryst Pharmaceuticals
  More Information

No publications provided

Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00705406     History of Changes
Other Study ID Numbers: BCX1812-212, HHS 0100200700032C
Study First Received: June 24, 2008
Results First Received: January 16, 2015
Last Updated: February 12, 2015
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
New Zealand: Medsafe
South Africa: Medicines Control Council

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases

ClinicalTrials.gov processed this record on July 27, 2015