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

Influenza Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00419263
• Other study ID #: BCX1812-211
• Status: Completed
• Phase: Phase 2
• First received: January 4, 2007
• Last updated: January 28, 2015
• Start date: January 2007
• Est. completion date: September 2007

Study information

• Verified date: January 2015
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

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).
• Peramivir 300 mg
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
• Placebo
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).

Locations

Country	Name	City	State
Canada	Calgary West Medical Cnetre Clinical Studies	Calgary	Alberta
Canada	Gain Medical Centre	Coquitlam	British Columbia
Canada	Belvedere Medicentre	Edmonton	Alberta
Canada	Castledowns Medicentre	Edmonton	Alberta
Canada	Hermitage Medicentres	Edmonton	Alberta
Canada	RJA Medicentres	Edmonton	Alberta
Canada	Source Unique Clinic	Hawkesbury	Ontario
Canada	Omnispec Clinical Reasearch Inc	Mirabel	Quebec
Canada	Prairie Clinical	Saskatoon	Saskatchewan
Canada	Clinique Medicale des Campus	Ste-Foy	Quebec
Canada	Manna Research	Toronto	Ontario
United States	Summa Health	Akron	Ohio
United States	Alliance Medical Center	Alliance	Nebraska
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Orange County Clinical Trials	Anaheim	California
United States	Integrated Medical Research, PC	Ashland	Oregon
United States	Georgia Clinical Research	Atlanta	Georgia
United States	Kentucky Pediatric / Adult Research	Bardstown	Kentucky
United States	Radiant Research	Birmingham	Alabama
United States	Alpine Clinical Research Center	Boulder	Colorado
United States	Bozeman Urgent Care Center	Bozeman	Montana
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Medical Center	Carmichael	California
United States	UMDNJ	Cherry Hill	New Jersey
United States	Sterling Research Group, LTD.	Cincinnati	Ohio
United States	Clinical Research of Southern Florida	Coral Gables	Florida
United States	New England Center for Clinical Research, Inc	Cranston	Rhode Island
United States	Paragon Clinical Research, Inc.	Cranston	Rhode Island
United States	Radiant Research	Dallas	Texas
United States	Research Across America	Dallas	Texas
United States	University Clinical Research-Deland, LLC	DeLand	Florida
United States	Pulmonary & Critical Care Associates	East Brunswick	New Jersey
United States	Radiant Research, Minneapolis	Edina	Minnesota
United States	Pacific Sleep Medicines Service	El Centro	California
United States	Florida Medical Research Institute	Gainesville	Florida
United States	Towngate Plaza Medical Center	Garland	Texas
United States	Baylor Clinic-Baylor College of Medicine	Houston	Texas
United States	Wishard Hospital	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Clopton Clinic	Jonesboro	Arkansas
United States	Research Across America at Oyster Point Family Health Center	Lancaster	Pennsylvania
United States	Central Kentucky Research Assoc, Inc	Lexington	Kentucky
United States	Benchmark Research	Metairie	Louisiana
United States	Midwest Family Physicians	Omaha	Nebraska
United States	Advanced Clinical Research Institute	Orange	California
United States	Radiant Research	Overland Park	Kansas
United States	Radiant Research	Philadelphia	Pennsylvania
United States	Primary Physicians Research, Inc	Pittsburgh	Pennsylvania
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	Benchmark Research	Sacramento	California
United States	J. Lewis Research, Inc. Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewis Research, Inc. Foothill Family Clinic South	Salt Lake City	Utah
United States	GSA Research	San Antonio	Texas
United States	Radiant Research San Antonio	San Antonio	Texas
United States	Radiant Research-San Antonio Northeast	San Antonio	Texas
United States	Pacific Sleep Medicine Services	San Diego	California
United States	Pacific Sleep Medicine Services	San Francisco	California
United States	Clinical Research Center	Sarasota	Florida
United States	Hillcrest Family Practice	Simpsonville	South Carolina
United States	Barnes-Jewish Hospital Emergency Department	St Louis	Missouri
United States	Medex Healthcare Research, Inc.	St. Louis	Missouri
United States	Radiant Research	St. Louis	Missouri
United States	Balbir Chahal M.D. ,P.A	Tomball	Texas
United States	Dynamed Clinical Research	Tomball	Texas
United States	Omega Medical Research	Warwick	Rhode Island
United States	George Washington Unviersity	Washington	District of Columbia
United States	J. Lewis Research, Inc./Southwest Family Medicine	West Jordan	Utah
United States	Palm Beach Research Center	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No