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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00419263
First received: January 4, 2007
Last updated: January 28, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Influenza
Drug: Peramivir 150 mg
Drug: Peramivir 300 mg
Drug: Placebo
Phase 2

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

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: Up to 14 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Resolution of Fever [ Time Frame: Up to 14 days ] [ Designated as safety issue: No ]
    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.

  • Time to Resumption of Ability to Perform Usual Activities [ Time Frame: Up to 14 days ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Day 2 in Influenza Virus Titer [ Time Frame: Baseline and approximately 24 hours after treatment ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline to Day 3 in Influenza Virus Titer [ Time Frame: Baseline and approximately 48 hours after treatment ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline to Day 5 in Influenza Virus Titer [ Time Frame: Baseline and approximately 96 hours after treatment ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline to Day 9 in Influenza Virus Titer [ Time Frame: Baseline and approximately 192 hours after treatment ] [ Designated as safety issue: No ]
    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).


Enrollment: 344
Study Start Date: January 2007
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: BCX1812
Placebo Comparator: Placebo Drug: Placebo
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00419263

  Show 69 Study Locations
Sponsors and Collaborators
BioCryst Pharmaceuticals
Investigators
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: Wayne Harper, MD Wake Research Associates, LLC
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 medicale 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: Monica Pierson, MD Radiant Research
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.
  More Information

No publications provided

Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00419263     History of Changes
Other Study ID Numbers: BCX1812-211
Study First Received: January 4, 2007
Results First Received: January 16, 2015
Last Updated: January 28, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by BioCryst Pharmaceuticals:
influenza
flu

ClinicalTrials.gov processed this record on March 26, 2015