Clinical trial NCT00419263: Evaluation of the Efficacy and Safety of Peramivir in Subjects With Uncomplicated Acute Influenza.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: influenza
flu
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-01-08
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to Alleviation of Symptoms (Kaplan-Meier Estimate)
timeFrame: Up to 14 days
Secondary outcomes:
measure: Time to Resolution of Fever
timeFrame: Up to 14 days
measure: Time to Resumption of Ability to Perform Usual Activities
timeFrame: Up to 14 days
measure: Change From Baseline to Day 2 in Influenza Virus Titer
timeFrame: Baseline and approximately 24 hours after treatment
measure: Change From Baseline to Day 3 in Influenza Virus Titer
timeFrame: Baseline and approximately 48 hours after treatment
measure: Change From Baseline to Day 5 in Influenza Virus Titer
timeFrame: Baseline and approximately 96 hours after treatment
measure: Change From Baseline to Day 9 in Influenza Virus Titer
timeFrame: Baseline and approximately 192 hours after treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Radiant Research
state: Alabama
city: Jonesboro
country: United States
facility: Clopton Clinic
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Anaheim
country: United States
facility: Orange County Clinical Trials
state: California
city: Carmichael
country: United States
facility: Medical Center
state: California
city: El Centro
country: United States
facility: Pacific Sleep Medicines Service
state: California
city: Orange
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Sacramento
country: United States
facility: Benchmark Research
state: California
city: San Diego
country: United States
facility: Pacific Sleep Medicine Services
state: California
city: San Francisco
country: United States
facility: Pacific Sleep Medicine Services
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: Washington
country: United States
facility: George Washington Unviersity
state: District of Columbia
city: Coral Gables
country: United States
facility: Clinical Research of Southern Florida
state: Florida
city: DeLand
country: United States
facility: University Clinical Research-Deland, LLC
state: Florida
city: Gainesville
country: United States
facility: Florida Medical Research Institute
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Sarasota
country: United States
facility: Clinical Research Center
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: Georgia Clinical Research
state: Georgia
city: Indianapolis
country: United States
facility: Wishard Hospital
state: Indiana
city: Overland Park
country: United States
facility: Radiant Research
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric / Adult Research
state: Kentucky
city: Lexington
country: United States
facility: Central Kentucky Research Assoc, Inc
state: Kentucky
city: Metairie
country: United States
facility: Benchmark Research
state: Louisiana
city: Edina
country: United States
facility: Radiant Research, Minneapolis
state: Minnesota
city: St Louis
country: United States
facility: Barnes-Jewish Hospital Emergency Department
state: Missouri
city: St. Louis
country: United States
facility: Medex Healthcare Research, Inc.
state: Missouri
city: St. Louis
country: United States
facility: Radiant Research
state: Missouri
city: Bozeman
country: United States
facility: Bozeman Urgent Care Center
state: Montana
city: Alliance
country: United States
facility: Alliance Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Midwest Family Physicians
state: Nebraska
city: Cherry Hill
country: United States
facility: UMDNJ
state: New Jersey
city: East Brunswick
country: United States
facility: Pulmonary & Critical Care Associates
state: New Jersey
city: Brooklyn
country: United States
facility: Brooklyn Hospital Center
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Akron
country: United States
facility: Summa Health
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Group, LTD.
state: Ohio
city: Ashland
country: United States
facility: Integrated Medical Research, PC
state: Oregon
city: Lancaster
country: United States
facility: Research Across America at Oyster Point Family Health Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Radiant Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Primary Physicians Research, Inc
state: Pennsylvania
city: Cranston
country: United States
facility: New England Center for Clinical Research, Inc
state: Rhode Island
city: Cranston
country: United States
facility: Paragon Clinical Research, Inc.
state: Rhode Island
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Simpsonville
country: United States
facility: Hillcrest Family Practice
state: South Carolina
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: Dallas
country: United States
facility: Radiant Research
state: Texas
city: Garland
country: United States
facility: Towngate Plaza Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor Clinic-Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: GSA Research
state: Texas
city: San Antonio
country: United States
facility: Radiant Research-San Antonio Northeast
state: Texas
city: San Antonio
country: United States
facility: Radiant Research San Antonio
state: Texas
city: Tomball
country: United States
facility: Balbir Chahal M.D. ,P.A
state: Texas
city: Tomball
country: United States
facility: Dynamed Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. Foothill Family Clinic South
state: Utah
city: West Jordan
country: United States
facility: J. Lewis Research, Inc./Southwest Family Medicine
state: Utah
city: Calgary
country: Canada
facility: Calgary West Medical Cnetre Clinical Studies
state: Alberta
city: Edmonton
country: Canada
facility: Belvedere Medicentre
state: Alberta
city: Edmonton
country: Canada
facility: Hermitage Medicentres
state: Alberta
city: Edmonton
country: Canada
facility: RJA Medicentres
state: Alberta
city: Edmonton
country: Canada
facility: Castledowns Medicentre
state: Alberta
city: Coquitlam
country: Canada
facility: Gain Medical Centre
state: British Columbia
city: Hawkesbury
country: Canada
facility: Source Unique Clinic
state: Ontario
city: Toronto
country: Canada
facility: Manna Research
state: Ontario
city: Mirabel
country: Canada
facility: Omnispec Clinical Reasearch Inc
state: Quebec
city: Ste-Foy
country: Canada
facility: Clinique Medicale des Campus
state: Quebec
city: Saskatoon
country: Canada
facility: Prairie Clinical
state: Saskatchewan
Study officials:
affiliation: Kentucky Pediatric/Adult Research
name: Stanley Block, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Kentucky Research Assoc, Inc
name: James Borders, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hillcrest Family Practice
name: Robert Broker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alpine Clinical Research Center
name: Paul Browstone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jacksonville Center For Clinical Research
name: Jeffry Jacqmein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Palm Beach Research Center
name: Isaac Marcadis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jacksonville Center For Clinical Research
name: Mark Stich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: GSA Research
name: George Atiee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Across America
name: Joe Blumenau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Center
name: John Champlin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J. Lewis Research, Inc. Foothill Family Clinic South
name: Shane Christensen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Advanced Clinical Research Institute
name: Steven Duckor, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Midwest Family Physicians
name: Lewis Eirinberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Sleep Medicine Services
name: Milton K. Erman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research
name: Stanley Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Omega Medical Research
name: David L. Fried, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Sleep Medicine Services, Inc.
name: Yury Furman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Research Associates, LLC
name: Wayne Harper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J. Lewis Research, Inc. Foothill Family Clinic
name: Dan C Henry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Clinical Research-Deland, LLC
name: John M. Hill, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clopton Clinic
name: Veryl Hodges, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Center
name: Reuben Holland, III, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research San Antonio
name: William Jennings, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor Clinic-Baylor College of Medicine
name: James Edmond Kelaher, MD,MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Hermitage Medicentres
name: Allan Kelly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Manna Research
name: Ben Lasko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Brooklyn Hospital Center
name: Mark Leber, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida Medical Research Institute
name: Larissa Lim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinique medicale des Campus
name: Alain Martel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Paragon Clinical Research, Inc.
name: Dennis Mikolich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sterling Research Group, LTD.
name: Julie Mullen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: George Washington University
name: David Parenti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research
name: Monica Pierson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barnes-Jewish Hospital Emergency Department
name: Robert Poirier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Benchmark Research
name: Ivan Rarick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Advanced Clinical Research Institute
name: Dennis Riff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Castledowns Medicentre
name: Q Rizvi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Sleep Medicine Services
name: Michael Rokeach, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wishard Hospital
name: Rawle Seupaul, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gain Medical Research Centre
name: Daniel Shu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Orange County Clinical Trials
name: Steve Sitar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Summa Emergency Associates Inc.
name: Kirk Stiffler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Omnispec clinical research Inc
name: Guy Tellier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Across America at Oyster Point Family Health Center
name: Michael Warren, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: J. Lewis Research, Inc./Southwest Family Medicine
name: Randall Watson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bozeman Urgent Care Center
name: John Michael Wise, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research
name: Chivers Woodruff, Jr., MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research
name: Bruce Berwald, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New England Center for Clinical Research, Inc
name: Frank Maggiacomo, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research
name: Barry Packman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research, Minneapolis
name: Sheila Rodstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Sleep Medicines Service
name: Bernardo Ng, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Towngate Plaza Medical Center
name: Gerardo Losoya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research-San Antonio Northeast
name: Francis X. Burch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Integrated Medical Research, PC
name: John P. Delgado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pulmonary & Critical Care Associates
name: Edward Fein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alliance Medical Center
name: Bruce D. Forney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medex Healthcare Research, Inc.
name: James E. Greenwald, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Medicine & Dentistry of New Jersey
name: Robert Hudrick, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Benchmark Research
name: Robert Jeanfreau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Georgia Clinical Research
name: Robert Kaufmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Calgary West Medical Centre Clinical Studies
name: Sy Lam, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Primary Physicians Research, Inc
name: Keith S. Reisinger, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Family Practice Medical Associates South
name: Keith S. Reisinger, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Dynamed Clinical Research
name: Earl Martin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Q & T Research Inc.
name: Jean-Sebastien Gauthier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research of Southern Florida
name: Jeffrey Rosen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New Orleans Medical
name: Gerald Burns, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Belvedere Medicentre
name: Stewart Behiel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Source Unique Clinic
name: Giuseppe D'Ignazio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Prairie Clinical
name: Indravadan Dattani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: RJA Medicentres
name: Roy A. Gritter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Balbir Chahal M.D. ,P.A.
name: Balbir Chahal, MD
role: PRINCIPAL_INVESTIGATOR
References: