Evaluation of the Efficacy and Safety of Peramivir in Subjects With Uncomplicated Acute Influenza.

A Phase II, Multicenter, Randomized, Double-Mask, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Intramuscular Peramivir in Subjects With Uncomplicated Acute Influenza.

This is a study for patients with flu who also have a fever as well as other flu symptoms. Patients must have had symptoms for less than 48 hours in order to participate. Patients will have two out of three chances of getting an active study treatment and the other third will receive a placebo (dummy drug). Nobody will know who gets the active drug and who gets the inactive drug. All patients will get supplies to treat symptoms of flu. Patients will need to be seen 5 more times after they are enrolled in the study.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Peramivir 150 mg; Drug: Peramivir 300 mg; Drug: Placebo

Detailed Description

Peramivir is a neuraminidase inhibitor that was previously shown to be effective in the treatment of human experimental influenza using an oral formulation. Parenteral formulations of peramivir (for intramuscular and intravenous injection) entered clinical development at the time of this Phase 2 study. A series of Phase 1 studies in human volunteers was completed that provided safety and pharmacokinetic results that supported the initiation of this Phase 2 multinational, randomized, double-mask study that compared the antiviral efficacy and safety of peramivir administered intramuscularly versus placebo in adults with uncomplicated acute influenza. Because of the unique pharmacokinetic and pharmacodynamic properties of peramivir - a long terminal half life in plasma and an extended duration of binding to the neuraminidase enzyme - subjects were randomized in a 1:1:1 ratio to receive a single dose of one of three treatments: peramivir 150 mg, peramivir 300 mg, and placebo. Study drug was administered as one 2-mL intramuscular injection in each gluteal muscle (total of 4 mL, injected in divided doses). This multinational study was originally to be conducted at approximately 80 sites in the US and Canada. When enrollment during the North American influenza season of 2006-2007 did not achieve the target, the study was extended to sites in Australia, New Zealand, South Africa, and Hong Kong.

• Study Type: Interventional
• Enrollment (Actual): 344
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3C3P1
      • Calgary West Medical Cnetre Clinical Studies
    • Edmonton, Alberta, Canada, T5COA3
      • Belvedere Medicentre
    • Edmonton, Alberta, Canada, T5COA3
      • Hermitage Medicentres
    • Edmonton, Alberta, Canada, T5N2N8
      • RJA Medicentres
    • Edmonton, Alberta, Canada, T5X3N5
      • Castledowns Medicentre
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
      • Gain Medical Centre
  • Ontario
    • Hawkesbury, Ontario, Canada, K6A1A1
      • Source Unique Clinic
    • Toronto, Ontario, Canada, M9W4L6
      • Manna Research
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Omnispec Clinical Reasearch Inc
    • Ste-Foy, Quebec, Canada, G1V4P9
      • Clinique Médicale des Campus
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7H 5M3
      • Prairie Clinical
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Radiant Research
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Clopton Clinic
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Anaheim, California, United States, 92801
      • Orange County Clinical Trials
    • Carmichael, California, United States, 95608
      • Medical Center
    • El Centro, California, United States, 92243
      • Pacific Sleep Medicines Service
    • Orange, California, United States, 92869
      • Advanced Clinical Research Institute
    • Sacramento, California, United States, 95816
      • Benchmark Research
    • San Diego, California, United States, 92121
      • Pacific Sleep Medicine Services
    • San Francisco, California, United States, 94105
      • Pacific Sleep Medicine Services
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington Unviersity
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of Southern Florida
    • DeLand, Florida, United States, 32720
      • University Clinical Research-Deland, LLC
    • Gainesville, Florida, United States, 32607
      • Florida Medical Research Institute
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32205
      • Jacksonville Center for Clinical Research
    • Sarasota, Florida, United States, 34239
      • Clinical Research Center
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Georgia Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Wishard Hospital
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Radiant Research
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric / Adult Research
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Assoc, Inc
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Radiant Research, Minneapolis
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital Emergency Department
    • St. Louis, Missouri, United States, 63124
      • Medex Healthcare Research, Inc.
    • St. Louis, Missouri, United States, 63141
      • Radiant Research
  • Montana
    • Bozeman, Montana, United States, 59715
      • Bozeman Urgent Care Center
  • Nebraska
    • Alliance, Nebraska, United States, 69301
      • Alliance Medical Center
    • Omaha, Nebraska, United States, 68154
      • Midwest Family Physicians
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • UMDNJ
    • East Brunswick, New Jersey, United States, 08816
      • Pulmonary & Critical Care Associates
  • New York
    • Brooklyn, New York, United States, 11201
      • Brooklyn Hospital Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Integrated Medical Research, PC
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Research Across America at Oyster Point Family Health Center
    • Philadelphia, Pennsylvania, United States, 19115
      • Radiant Research
    • Pittsburgh, Pennsylvania, United States, 15241
      • Primary Physicians Research, Inc
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • New England Center for Clinical Research, Inc
    • Cranston, Rhode Island, United States, 02920
      • Paragon Clinical Research, Inc.
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Simpsonville, South Carolina, United States, 29681
      • Hillcrest Family Practice
  • Texas
    • Dallas, Texas, United States, 75234
      • Research Across America
    • Dallas, Texas, United States, 75235
      • Radiant Research
    • Garland, Texas, United States, 75041
      • Towngate Plaza Medical Center
    • Houston, Texas, United States, 77030
      • Baylor Clinic-Baylor College of Medicine
    • San Antonio, Texas, United States, 78213
      • Gsa Research
    • San Antonio, Texas, United States, 78217
      • Radiant Research-San Antonio Northeast
    • San Antonio, Texas, United States, 78229
      • Radiant Research San Antonio
    • Tomball, Texas, United States, 77375
      • Balbir Chahal M.D. ,P.A
    • Tomball, Texas, United States, 77375
      • Dynamed Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. Foothill Family Clinic South
    • West Jordan, Utah, United States, 84084
      • J. Lewis Research, Inc./Southwest Family Medicine

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
• 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. However, this requirement is waived if the subject has a history of fever within the 24 hours prior to screening and has been administered antipyretic(s) in the 6 hours prior to screening.
• Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of any severity (mild, moderate, or severe)
• Presence of at least one constitutional symptom (headache, malaise, myalgia, sweats and/or chills, or fatigue) of any severity (mild, moderate, or severe)
• Onset of illness no more than 48 hours before presentation. Note: Time of onset of illness is defined as either (1) the time when the temperature (either oral or rectal) was first measured as elevated (at least one ºC of elevation-oral temperature), OR (2) the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
• Rapid Antigen Test (RAT) performed on an adequate specimen collected from an anterior nasal swab is positive. A negative initial RAT may be repeated within one hour of obtaining a negative result. A second negative RAT result will exclude the subject from evaluation for enrollment.

• Females of childbearing potential must report one of the following:

  • Be surgically sterile
  • 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
  • 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
  • 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.

Exclusion Criteria:

• Women who are breast-feeding
• History of diagnosed chronic obstructive pulmonary disease or diagnosis of severe persistent asthma
• History of chronic renal impairment requiring hemodialysis or known or suspected to have moderate or severe renal impairment (actual or estimated creatinine clearance <50 mL/min)
• History of congestive heart failure requiring daily pharmacotherapy with symptoms consistent with New York Heart Association Class II, III, or IV within the past 12 months
• Immunocompromised status due to illness or previous organ transplant
• Current use of systemic immunosuppressive medications (except inhaled corticosteroids)
• Use of rimantadine, amantadine, zanamivir, or oseltamivir in the past 7 days
• Immunized against influenza with live attenuated virus vaccine (FluMist®) in the previous 21 days
• Clinical evidence of active bacterial infection at any body site requiring therapy with oral or systemic antibiotics
• Clinically significant signs of acute respiratory distress
• Clinically significant signs of acute cardiac disease
• Screening ECG which suggests acute ischemia or presence of medically significant dysrhythmia
• Presence of a chronic disease or illness(es) with either clinical or historical evidence of recent exacerbation of such disease(s) or illness(es) or lack of control of such disease(s) or illness(es)
• History of hepatitis B, hepatitis C, or human immunodeficiency virus infection
• History of alcohol abuse or drug addiction within 1 year prior to admission in the study
• Participation in a study of any investigational drug within the last 30 days
• Positive urine pregnancy test

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
Placebo Comparator: Placebo	Drug: Placebo; Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Experimental: Peramivir 150 mg	Drug: Peramivir 150 mg; Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).; Other Names: BCX1812
Experimental: Peramivir 300 mg	Drug: Peramivir 300 mg; Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).; Other Names: BCX1812

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Alleviation of Symptoms (Kaplan-Meier Estimate)	Descriptive statistics for the primary efficacy variables were tabulated by treatment group. Alleviation of symptoms was determined by data recorded in the Subject Diary. Treatment differences were assessed using a Cox Regression model with effects for current smoking behavior, treatment, and geographic region. Subjects who did not experience alleviation of symptoms were censored at the date of their last assessment. A Bonferroni adjustment for the primary comparisons of each active dose with placebo was performed.	Up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Resolution of Fever	The time to resolution of fever (defined as the number of hours from initiation of study drug until temperature is less than 37.2 degrees C [99.0 degrees F] and no antipyretic medications had been taken in the previous 12 hours) was estimated using the method of Kaplan-Meier. Differences between the treatment groups were assessed using the log rank statistic controlling for current smoking behavior. Subjects who did not have resolution of fever were censored at the time of the last assessment. No adjustment for multiple comparisons was performed.	Up to 14 days
Time to Resumption of Ability to Perform Usual Activities	The time to resumption of a subject's self-assessed ability to perform his or her usual activities was estimated using the method of Kaplan-Meier. Differences between the treatment groups were assessed using the log rank statistic controlling for current smoking behavior. Subjects who were not able to resume performance of usual activities were censored at the time of the last assessment.	Up to 14 days
Change From Baseline to Day 2 in Influenza Virus Titer	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).	Baseline and approximately 24 hours after treatment
Change From Baseline to Day 3 in Influenza Virus Titer	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).	Baseline and approximately 48 hours after treatment
Change From Baseline to Day 5 in Influenza Virus Titer	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).	Baseline and approximately 96 hours after treatment
Change From Baseline to Day 9 in Influenza Virus Titer	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).	Baseline and approximately 192 hours after treatment

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Wayne Harper, MD, Wake Research Associates, LLC; Principal Investigator: Monica Pierson, MD, Radiant Research; Principal Investigator: Stanley Block, MD, Kentucky Pediatric/Adult Research; Principal Investigator: James Borders, MD, Central Kentucky Research Assoc, Inc; Principal Investigator: Robert Broker, MD, Hillcrest Family Practice; Principal Investigator: Paul Browstone, MD, Alpine Clinical Research Center; Principal Investigator: Jeffry Jacqmein, MD, Jacksonville Center for Clinical Research; Principal Investigator: Isaac Marcadis, MD, Palm Beach Research Center; Principal Investigator: Mark Stich, MD, Jacksonville Center for Clinical Research; Principal Investigator: George Atiee, MD, Gsa Research; Principal Investigator: Joe Blumenau, MD, Research Across America; Principal Investigator: John Champlin, MD, Medical Center; Principal Investigator: Shane Christensen, MD, J. Lewis Research, Inc. Foothill Family Clinic South; Principal Investigator: Steven Duckor, MD, Advanced Clinical Research Institute; Principal Investigator: Lewis Eirinberg, MD, Midwest Family Physicians; Principal Investigator: Milton K. Erman, MD, Pacific Sleep Medicine Services; Principal Investigator: Stanley Cohen, MD, Radiant Research; Principal Investigator: David L. Fried, MD, Omega Medical Research; Principal Investigator: Yury Furman, MD, Pacific Sleep Medicine Services, Inc.; Principal Investigator: Dan C Henry, MD, J. Lewis Research, Inc. Foothill Family Clinic; Principal Investigator: John M. Hill, MD, University Clinical Research-Deland, LLC; Principal Investigator: Veryl Hodges, DO, Clopton Clinic; Principal Investigator: Reuben Holland, III, MD, Clinical Research Center; Principal Investigator: William Jennings, MD, Radiant Research San Antonio; Principal Investigator: James Edmond Kelaher, MD,MPH, Baylor Clinic-Baylor College of Medicine; Principal Investigator: Allan Kelly, MD, Hermitage Medicentres; Principal Investigator: Ben Lasko, MD, Manna Research; Principal Investigator: Mark Leber, MD, The Brooklyn Hospital Center; Principal Investigator: Larissa Lim, MD, Florida Medical Research Institute; Principal Investigator: Alain Martel, MD, Clinique Médicale des Campus; Principal Investigator: Dennis Mikolich, MD, Paragon Clinical Research, Inc.; Principal Investigator: Julie Mullen, MD, Sterling Research Group, Ltd.; Principal Investigator: David Parenti, MD, George Washington University; Principal Investigator: Robert Poirier, MD, Barnes-Jewish Hospital Emergency Department; Principal Investigator: Ivan Rarick, MD, Benchmark Research; Principal Investigator: Dennis Riff, MD, Advanced Clinical Research Institute; Principal Investigator: Q Rizvi, MD, Castledowns Medicentre; Principal Investigator: Michael Rokeach, MD, Pacific Sleep Medicine Services; Principal Investigator: Rawle Seupaul, MD, Wishard Hospital; Principal Investigator: Daniel Shu, MD, Gain Medical Research Centre; Principal Investigator: Steve Sitar, MD, Orange County Clinical Trials; Principal Investigator: Kirk Stiffler, MD, Summa Emergency Associates Inc.; Principal Investigator: Guy Tellier, MD, Omnispec clinical research inc; Principal Investigator: Michael Warren, MD, Research Across America at Oyster Point Family Health Center; Principal Investigator: Randall Watson, MD, J. Lewis Research, Inc./Southwest Family Medicine; Principal Investigator: John Michael Wise, MD, Bozeman Urgent Care Center; Principal Investigator: Chivers Woodruff, Jr., MD, Radiant Research; Principal Investigator: Bruce Berwald, MD, Radiant Research; Principal Investigator: Frank Maggiacomo, DO, New England Center for Clinical Research, Inc; Principal Investigator: Barry Packman, MD, Radiant Research; Principal Investigator: Sheila Rodstein, MD, Radiant Research, Minneapolis; Principal Investigator: Bernardo Ng, MD, Pacific Sleep Medicines Service; Principal Investigator: Gerardo Losoya, MD, Towngate Plaza Medical Center; Principal Investigator: Francis X. Burch, MD, Radiant Research-San Antonio Northeast; Principal Investigator: John P. Delgado, MD, Integrated Medical Research, PC; Principal Investigator: Edward Fein, MD, Pulmonary & Critical Care Associates; Principal Investigator: Bruce D. Forney, MD, Alliance Medical Center; Principal Investigator: James E. Greenwald, MD, Medex Healthcare Research, Inc.; Principal Investigator: Robert Hudrick, DO, University of Medicine & Dentistry of New Jersey; Principal Investigator: Robert Jeanfreau, MD, Benchmark Research; Principal Investigator: Robert Kaufmann, MD, Georgia Clinical Research; Principal Investigator: Sy Lam, MD, Calgary West Medical Centre Clinical Studies; Principal Investigator: Keith S. Reisinger, MD, MPH, Primary Physicians Research, Inc; Principal Investigator: Keith S. Reisinger, MD, MPH, Family Practice Medical Associates South; Principal Investigator: Earl Martin, MD, Dynamed Clinical Research; Principal Investigator: Jean-Sebastien Gauthier, MD, Q & T Research Inc.; Principal Investigator: Jeffrey Rosen, MD, Clinical Research of Southern Florida; Principal Investigator: Gerald Burns, MD, New Orleans Medical; Principal Investigator: Stewart Behiel, MD, Belvedere Medicentre; Principal Investigator: Giuseppe D'Ignazio, MD, Source Unique Clinic; Principal Investigator: Indravadan Dattani, MD, Prairie Clinical; Principal Investigator: Roy A. Gritter, MD, RJA Medicentres; Principal Investigator: Balbir Chahal, MD, Balbir Chahal M.D. ,P.A.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: January 4, 2007
• First Submitted That Met QC Criteria: January 5, 2007
• First Posted (Estimate): January 8, 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; Peramivir
• Other Study ID Numbers: BCX1812-211