Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza

Phase II, Multicenter, Randomized, Double-Mask, Double-Dummy Study Comparing Efficacy and Safety of Intravenous Peramivir Once Daily Versus Oral Oseltamivir Twice Daily in Adults With Acute Serious or Potentially Life-Threatening Influenza

This study has been designed as a randomized, double-blind, controlled, study to evaluate the efficacy and safety of two once daily intravenous peramivir regimens (200 mg and 400 mg) versus oral oseltamivir phosphate (75 mg twice daily) in hospitalized subjects with acute serious or potentially life threatening influenza. Study treatments will be provided for up to 5 consecutive days.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Peramivir 200 mg; Drug: Peramivir 400 mg; Drug: Oseltamivir

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
    • Wentworthville, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Cairns Base Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Daw Park, South Australia, Australia, 5041
      • Repatriation General Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6060
      • Sir Charles Gairdner Hospital
• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 3T1
      • Kelowna General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences-McMaster University Medical Centre
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton-L424
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital / Toronto Medical Laboratories
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Center de Sante et des Services Sociaux de Chicoutimi
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre de sante et de services sociaux Rimouski-Neigette (CSSSRN)
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Division of Infectious Diseases
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong
    • United Christian Hospital
  • Shatin - New Territories, Hong Kong
    • The Prince of Wales Hospital
• New Zealand
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Hamilton, New Zealand
    • Waikato Hospital
  • Tauranga, New Zealand, 3110
    • Tauranga Hospital
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 169608
    • National University Hospital
• South Africa
  • E. Cape
    • Port Elizabeth, E. Cape, South Africa, 6020
      • Global Clinical Trial Center
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Genclin Corporation
  • Gauteng
    • Benoni, Gauteng, South Africa, 1500
      • Benmed / Pentagon Hospital
    • Cape Town, Gauteng, South Africa, 1724
      • Private Practice
    • Johannesburg,, Gauteng, South Africa, 2001
      • Newgate Centre
    • Krugersdorp, Gauteng, South Africa, 1739
      • DJW Navorsing
    • Pretoria, Gauteng, South Africa, 0001
      • Medforum Hospital
    • Pretoria, Gauteng, South Africa, 0084
      • Eugene Marais Hospital
    • Pretoria, Gauteng, South Africa, 0186
      • Global Clinical Trials (GCT)
    • Soweto, Gauteng, South Africa, 1818
      • Dr Bhorat
  • KZ-Natal
    • Durban, KZ-Natal, South Africa, 4001
      • Sebastian, P
  • Mpumalanga
    • Nelspruit, Mpumalanga, South Africa, 1201
      • Eksteen, MC
  • W Cape
    • Worcester, W Cape, South Africa, 6850
      • Dr. L.J. van Zyl
  • WC
    • Cape town, WC, South Africa, 7460
      • N1 City Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Pulmonary Associates of Mobile, P.C.
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • St. Bernards Research Center/Clopton Clinic
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Orange, California, United States, 92868
      • Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center, Department of Emergency Medicine
    • San Jose, California, United States, 95124
      • Good Samaritan Hospital
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center, Clinical Research Unit
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Regional Healthcare
    • Tampa, Florida, United States, 33612
      • James A. Haley Veterans Hospital, Department of Infectious Disease
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta, P.C.
    • Savannah, Georgia, United States, 31405
      • St. Joseph's/Candler Health System, Inc.
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Idaho Falls Infectious Diseases, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Springfield, Illinois, United States, 62701
      • Springfield Clinic, LLP
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Infectious Disease Of Indiana, Psc
    • Indianapolis, Indiana, United States, 46202
      • Wishard Hospital/Indiana University
  • Louisiana
    • Natchitoches, Louisiana, United States, 71457
      • Natchitoches Internal Medicine
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center-Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • VA Maryland Health Care System
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Detroit, Michigan, United States, 48201
      • Wayne State University School of Medicine
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital Troy
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group, PLLC
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center, Department of Infectious Disease
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • University of New Mexico
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Rochester, New York, United States, 14621-3001
      • Rochester General Hospital/University of Rochester
  • Ohio
    • Cleveland, Ohio, United States, 44106-5083
      • University Hospitals Case Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Lowcountry Infectious Diseases, P.A.
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Center
  • Virginia
    • Salem, Virginia, United States, 24153
      • Veterans Affairs Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • Franciscan Health System
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449-5703
      • Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years of age, male or female
• Able to provide informed consent, or for whom consent may be provided by guardian
• Presence of fever at time of screening of ≥38.0°C (≥ 100.0°F) taken orally, or ≥38.5°C (≥101.2°F) taken rectally. This requirement is waived if the subject has (1) a history of fever within 24 hours prior to screening and administered any antipyretic(s) in the 24 hours prior to screening, or (2) has no history of documented fever as defined above, but reports a symptom of feverishness at some time during 48 hours prior to screening
• Presence of at least 1 respiratory symptom (cough, sore throat, nasal congestion/symptoms) of any severity (mild, moderate, severe)
• Presence of at least 1 constitutional symptom (headache, myalgia, feverishness, malaise, fatigue) of any severity (mild, moderate, severe)
• Onset of illness no more than 72 hours before presentation. Time of onset of illness defined as either (1) the time when temperature (oral or rectal) was elevated (at least 1°C of elevation-oral temperature), OR (2) the time when the subject experienced the presence of at least 1 respiratory symptom AND the presence of at least 1 constitutional symptom
• Presence of 1 or more of the following factors in a subject willing to be hospitalized for inpatient observation and treatment:
• Age ≥60 years
• Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy
• History of congestive heart failure with or without medically significant recent change in cardiac status, but without signs or symptoms compatible with NYHA Class IV functional status
• Presence of diabetes mellitus, clinically stable or unstable
• Transcutaneous oxygen saturation <94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value
• Systolic blood pressure <90 mmHg
• Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care
• Positive rapid antigen test (RAT) for influenza A and/or influenza B (using an approved test kit) or other test for influenza virus antigen performed in a clinical laboratory at the screening/enrollment evaluation
• Females of childbearing potential must report one of the following:
• Be surgically sterile or clinically post-menopausal
• Have been sexually abstinent 4 weeks prior to date of screening evaluation and be willing to remain abstinent through 4 weeks after study-drug administration for all perimenopausal women or women of child-bearing potential
• Use oral contraceptives or other form of hormonal birth control including hormonal vaginal rings or transdermal patches and have been using these for 3 months prior through 4 weeks after study-drug administration for all perimenopausal women or women of child-bearing potential
• Use an intra-uterine device (IUD), or adequate barrier contraception (or double-barrier method such as condom or diaphragm with spermicidal gel or foam) as birth control 4 weeks prior to date of screening evaluation through 4 weeks after study drug administration for all perimenopausal women or women of child-bearing potential

Exclusion Criteria:

• Immunized against influenza with live attenuated virus vaccine in the previous weeks
• Treatment with any dose(s) of rimantadine, amantadine, zanamivir, or oseltamivir in the previous 7 days
• Current clinical evidence of a recognized or suspected acute non-influenzal infectious illness with onset prior to Screening
• Serum creatinine laboratory result at Screening >1.6 mg/dL or a result >25% above the upper limit of normal for the laboratory performing the test
• History of clinically significant proteinuria (≥1000 mg/24 hrs)
• History of moderate or severe renal impairment and/or previous clinical laboratory data indicating an estimated creatinine clearance <50 mL/min during the previous 12 months
• Electrocardiogram (ECG) at Screening visit showing evidence of acute ischemia, or presence of a medically significant dysrhythmia
• Presence of cardiac signs or symptoms compatible with NYHA Class III or Class IV functional status for congestive heart failure or angina (see NYHA Appendix V)
• Presence of diagnosed COPD or other chronic lung condition requiring either continuous or intermittent oxygen therapy as an outpatient. Note: Subjects who are determined to require acute supplemental oxygen therapy at the time of Screening and/or at hospital admission may be enrolled, if exclusion criteria #13 or #14 are not applicable.
• History of organ transplantation during the previous 12 months
• Known HIV infection with most recent CD4+ T-cell count ≤350 cells/mL
• History of diagnosis of any type of cancer (hematologic or solid tumor), that has required chemotherapy or radiation therapy in the previous 12 months, excluding non-melanomatous localized skin cancer
• Presence of ongoing requirement for chronic mechanical ventilation, either via oral or nasotracheal intubation or via tracheostomy, or chronic or intermittent requirement for BiPAP (bilevel positive airway pressure) at screening. Note: Subjects who require intermittent CPAP treatment for sleep apnea (without oxygen supplementation) may be enrolled
• Subjects who require acute mechanical ventilatory support of any type at the time of screening.
• History of alcohol abuse or drug addiction during the previous 12 months
• Participation in a clinical study of an experimental medication or other treatment during the previous 4 weeks
• Previous treatment with intravenous or intramuscular peramivir
• Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding
• Subjects who have been hospitalized due to a condition other than acute influenza and in whom influenza is diagnosed during hospitalization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Peramivir 200 mg; Peramivir 200 mg administered intravenously once daily for 5 days (5 doses)	Drug: Peramivir 200 mg; Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment
Experimental: Arm 2: Peramivir 400 mg; Peramivir 400 mg administered intravenously once daily for 5 days (5 doses)	Drug: Peramivir 400 mg; Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 ml)
Experimental: Arm 3: Oseltamivir; Oseltamivir 75 mg oral suspension administered orally twice daily for 5 days (10 doses)	Drug: Oseltamivir; Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinical Stability (Kaplan-Meier Estimate)	Time to clinical stability was summarized overall and for individual clinical signs for each treatment group using the method of Kaplan Meier. Subjects who did not experience clinical stability were censored at the date of their last non-missing assessment during the study (whether this assessment occurred as an inpatient or as an outpatient).	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Scores of Symptoms of Influenza	Descriptive statistics for the change from baseline in each of the 7 symptoms of influenza (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]) were tabulated by treatment group. Missing data were excluded.	Baseline, Days 2, 3, 4, 5, 10, and 14
Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate)	Changes in each subject's ability to perform usual activities as determined from the visual analog scale (0 to 10, where 0 indicated subject was unable to perform usual activities at all and 10 indicated subject was able to perform all usual activities fully) were summarized by study visit and treatment group. The time to resumption of a subject's ability to perform usual activities was estimated using the method of Kaplan Meier. Subjects who did not return to the pre-study level of performance of usual activities were censored at the time of their last assessment. (Note: N is the number of ITTI participants with available data).	14 days
Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study)	The number of subjects with clinical relapse, defined as changes in 2 or more signs of clinical stability to values outside the range of normalization criteria for a duration of at least 12 consecutive hours after clinical stability had been attained, were summarized by treatment group.	14 days
Time to Hospital Discharge (Kaplan-Meier Estimate)	Time to discharge from hospital was estimated using the method of Kaplan Meier. Subjects who were not discharged from the hospital were censored at the time of their last assessment.	14 days
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined)	Reduction in viral shedding, assessed as the change in quantitative viral titers and defined as the time-weighted change from baseline in TCID50/mL, was summarized for each treatment group.	Baseline, and 12, 24, 36, 48, 72, and 96 hours

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals

Publications and helpful links

General Publications

• Ison MG, Hui DS, Clezy K, O'Neil BJ, Flynt A, Collis PJ, Simon TJ, Alexander WJ. A clinical trial of intravenous peramivir compared with oral oseltamivir for the treatment of seasonal influenza in hospitalized adults. Antivir Ther. 2013;18(5):651-61. doi: 10.3851/IMP2442. Epub 2012 Oct 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: March 27, 2007
• First Submitted That Met QC Criteria: March 28, 2007
• First Posted (Estimate): March 29, 2007

Study Record Updates

• Last Update Posted (Estimate): February 12, 2015
• Last Update Submitted That Met QC Criteria: January 28, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: influenza; flu
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir; Peramivir
• Other Study ID Numbers: BCX1812-201