Acute, Uncomplicated Human Influenza Clinical Trial
Official title:
A Phase II, Multicenter, Randomized, Placebo -Controlled, Study To Evaluate The Efficacy and Safety Of Intramuscular Peramivir 600 mg In Subjects With Uncomplicated Acute Influenza
The purpose of this study is to determine whether peramivir is safe and effective in the treatment of uncomplicated seasonal influenza.
| Status | Completed |
| Enrollment | 405 |
| Est. completion date | October 2009 |
| Est. primary completion date | April 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Male and non-pregnant female subjects age =18 years. - A positive Influenza A or B Rapid Antigen Test (RAT) performed with a commercially available test kit on an adequate anterior nasal specimen, in accordance with the manufacturer's instructions. A negative initial RAT should be repeated within one hour. - 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. A subject self-report of a history of fever or feverishness within the 24 hours prior to screening will also qualify for enrollment in the absence of documented fever at the time of screening. - Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of at least moderate severity. - Presence of at least one constitutional symptom (myalgia [aches and pains], headache, feverishness, or fatigue) of at least moderate severity. - Onset of symptoms no more than 36 hours before presentation for screening. - Written informed consent. Exclusion Criteria: - Women who are pregnant or breast-feeding. - Presence of clinically significant signs of acute respiratory distress - History of severe chronic obstructive pulmonary disease (COPD) or severe persistent asthma. - History of heart failure or angina requiring daily pharmacotherapy with symptoms consistent with New York Heart Association Class III or IV functional status within the past 12 months. - Screening ECG which suggests acute ischemia or presence of medically significant dysrhythmia. - History of chronic renal impairment requiring hemodialysis and/or known or suspected to have moderate or severe renal impairment (actual or estimated creatinine clearance <50 mL/min). - Clinical evidence of worsening of any chronic medical condition (temporally associated with the onset of symptoms of influenza) which, in the investigator's opinion, indicates that such finding(s) could represent complications of influenza. - Current clinical evidence, including clinical signs and/or symptoms consistent with otitis, bronchitis, sinusitis and/or pneumonia, or active bacterial infection at any body site that requires therapy with oral or systemic antibiotics. - Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy which would include oral or systemic treatment with > 10 mg prednisone or equivalent on a daily basis within 30 days of screening. - Currently receiving treatment for viral hepatitis B or viral hepatitis C. - Presence of known HIV infection with a CD4 count <350 cell/mm3. - Current therapy with oral warfarin or other systemic anticoagulant. - Receipt of any doses of rimantadine, amantadine, zanamivir, or oseltamivir in the 7 days prior to screening. - Immunized against influenza with live attenuated virus vaccine (FluMist®) in the previous 21 days. - Immunized against influenza with inactivated virus vaccine within the previous 14 days. - Receipt of any intramuscular injection with the previous 7 days. - History of alcohol abuse or drug addiction within 1 year prior to admission in the study. - Participation in a previous study of intramuscular or intravenous peramivir or previous participation in this study. - Participation in a study of any investigational drug or device within the last 30 days. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Athelstone Medical Clinic | Adelaide | |
| Australia | Rivercity Private Hospital Specialist | Auchenflower | Queensland |
| Australia | Pacific Medical Centre Blacktown | Blacktown | New South Wales |
| Australia | Trialworks Clinical Research Services | Brisbane | |
| Australia | Dr Doongs Surgery | Burwood | |
| Australia | Caboolture Clinical Research Centre | Caboolture | Queensland |
| Australia | Health Services -University of Melbourne | Carlton | Victoria |
| Australia | East Sydney Doctors | Darlinghurst | New South Wales |
| Australia | Holdsworth House Medical Practice | Darlinghurst | |
| Australia | Symbion Pathology | Hurtsville | New South Wales |
| Australia | Peninsula Specialist Centre | Kpparing | Queensland |
| Australia | Doctors of Ivanhoe, | Melbourne | |
| Australia | Lung Institute of Western Australia, | Nedlands | |
| Australia | Pitt Street Merrylands Medical Centre | Sydney | |
| Australia | Peninsula Medical Centre | Umina | New South Wales |
| New Zealand | Greenhithe Medical Centre | Auckland | |
| New Zealand | Southern Clinical Trials Ltd | Christchurch | |
| New Zealand | St George's Hospital | Christchurch | |
| New Zealand | Caversham Medical Centre | Dunedin | |
| New Zealand | Bairds Road Family Health Care | Rotorua | |
| New Zealand | Dr. Gillies | Rotorua | |
| New Zealand | Hinemoa House Family Health Centre | Rotorua | |
| South Africa | Dr. van Rensburg | Amanzimtoti | |
| South Africa | Benmed Park Clinic | Benoni | |
| South Africa | Jsha Research | Bloemfontein | |
| South Africa | Quinta-Research | Bloemfontein | Free State |
| South Africa | Armansis Medical Centre | Brits | |
| South Africa | NHC Medical Centre | Bryanston | Gauteng |
| South Africa | Cape Clinical Trial, Bishop Lavis Day Hospital | Cape town | |
| South Africa | First House | Cape Town | |
| South Africa | Kaapzicht Centre | Cape Town | W. Cape |
| South Africa | Syzygy SMO Intercare Medical and Dental Centre | Cape Town | W. Cape |
| South Africa | Dr. Janari | Durban | |
| South Africa | Synapta Clinical Research Centre | Durban | |
| South Africa | Vawda, Z.FA | Durban | KZ-Natal |
| South Africa | Nortje, MD | Goodwood | Capetown |
| South Africa | Greenbury Medical Centre | Greenbury | Durban |
| South Africa | Dr. Makan | Johannesburg | |
| South Africa | Newgate Centre | Johannesburg | |
| South Africa | le Clus, MD | Kempton Park | Pretoria |
| South Africa | R. Dulabh, MD | Klipspruit West | Gauteng |
| South Africa | DJW Navorsing | Noordheuwel | Krugersdorp |
| South Africa | GCT Trials, Mercantile Hospital no 9 | Port Elizabeth | |
| South Africa | Dr. de Bruin | Pretoria | |
| South Africa | Dr. Nel | Pretoria | |
| South Africa | Emmed Research | Pretoria | |
| South Africa | Westmed Clinical Trial Centre, Pretoria West Medicross Building | Pretoria | |
| South Africa | Wilhase, AC | Reigerpark | Gauteg |
| South Africa | Dr. Fouche | Roodepoort | |
| South Africa | Dr. de Villiers | Scottburgh | |
| South Africa | Sebastian, MD | Silverglen | Durban |
| South Africa | Dr. Bhorat | Soweto | |
| South Africa | Sunnyside Medi-Clinic | Sunnyside Pretoria | Pretoria |
| South Africa | Pillay, MD | Verulam | Kwa Zulu Natal |
| South Africa | Clinical Project Research SA (Pty) Ltd. | Worcester | W. Cape |
| South Africa | Clinical Projects Research SA Ltd | Worcester | |
| United States | Integrated Medical Research, PC | Ashland | Oregon |
| United States | Acadia Clinical Research | Bangor | Maine |
| United States | Gulf Coast Research, LLC | Baton Rouge | Louisiana |
| United States | Northwest Clinical Research Center | Bellevue | Washington |
| United States | Impact Clinical Trials | Beverly Hills | California |
| United States | Greystone Medical Research, LLC | Birmingham | Alabama |
| United States | West Alabama Research, Inc. | Birmingham | Alabama |
| United States | Dr. Arthur Davida | Bloomingdale | Illinois |
| United States | Alpine Research Center | Boulder | Colorado |
| United States | Bozeman Urgent Care Center | Bozeman | Montana |
| United States | Holston Medical Group | Bristol | Tennessee |
| United States | Miray Medical Center | Brockton | Massachusetts |
| United States | DiscoveResearch, Inc. | Bryan | Texas |
| United States | Mercury Street Medical Group, PLLC | Butte | Montana |
| United States | Community Medical Associates, LLC | Canfield | Ohio |
| United States | Medcenter | Carmichael | California |
| United States | 1st Allergy and Clinical Research Center | Centennial | Colorado |
| United States | Clarksburg Medical Center | Clarksburg | Maryland |
| United States | Southeast Regional Research Group | Columbus | Georgia |
| United States | Clinical Research of South Florida | Coral Gables | Florida |
| United States | Corpus Christi Family Wellness Center, Research Division | Corpus Christi | Texas |
| United States | New England Center for Clinical Research, Inc. | Cranston | Rhode Island |
| United States | Notheast Clinical Research | Cumberland | Rhode Island |
| United States | Allergy/Immunology Research Center of North Texas | Dallas | Texas |
| United States | Detroit Receiving Hospital, UHC 6G | Detroit | Michigan |
| United States | Medical Associates Clinic | Dubuque | Iowa |
| United States | Prairie Fields Family Medicine, P.C. | Fremont | Nebraska |
| United States | Towngate Plaza Medical Center | Garland | Texas |
| United States | Bland Clinic | Greensboro | North Carolina |
| United States | Kentucky Lung Clinic | Hazard | Kentucky |
| United States | West Houston Clinical Research | Houston | Texas |
| United States | Idaho Falls Infectious Diseases | Idaho Falls | Idaho |
| United States | Investigators Research Group, LLC | Indianapolis | Indiana |
| United States | Jacksonville Center for Clinical Research | Jacksonville | Florida |
| United States | Westside Center for Clinical Research | Jacksonville | Florida |
| United States | United Medical Associates | Johnson City | New York |
| United States | Clinical Partners, LLC | Johnston | Rhode Island |
| United States | Clopton Clinic | Jonesboro | Arkansas |
| United States | NEA Clinic | Jonesboro | Arkansas |
| United States | Impact Clinical Trials, Las Vegas | Las Vegas | Nevada |
| United States | North Central Arkansas Medical Associates | Mountain Home | Arkansas |
| United States | Olive Branch Family Medical Center | Olive Branch | Mississippi |
| United States | Dean Medical Center | Oregon | Wisconsin |
| United States | Urgent Care of Green County, PLLC | Owasso | Oklahoma |
| United States | Center for Clinical Trials, LLC | Paramount | California |
| United States | University Clinical Research, Inc. | Pembroke Pines | Florida |
| United States | NextCare Institute for Clinical Research | Phoenix | Arizona |
| United States | DMI Research, Inc. | Pinellas Park | Florida |
| United States | Health Concepts | Rapid City | South Dakota |
| United States | Twelve Corners Internal Medicine | Rochester | New York |
| United States | William Beaumont Hospital | Royal Oak | Michigan |
| United States | J. Lewis Research, Inc., FirstMed | Salt Lake City | Utah |
| United States | J. Lewis Research, Inc./FirstMed East | Salt Lake City | Utah |
| United States | J. Lewis Research, Inc./Foothill Family Clinic South | Salt Lake City | Utah |
| United States | J. Lewis Research, Inc./Foothill Family Clinic South | Salt Lake City | Utah |
| United States | Texas Medical Research Associates, LLC | San Antonio | Texas |
| United States | Coastal Medical Research Group, Inc. | San Luis Obispo | California |
| United States | Southeast Regional Research Group | Savannah | Georgia |
| United States | Heart of America Research | Shawnee | Kansas |
| United States | Hillcrest Clinical Research, LLC | Simpsonville | South Carolina |
| United States | Pivotal Clinical Research, LLC | Souderton | Pennsylvania |
| United States | KMED Research | St. Claire Shores | Michigan |
| United States | Wilker/Powers Center for Clinical Studies, d/b/a ProHealth Clinical Studies | St. Cloud | Florida |
| United States | Advanced Health Care Services, Inc | Thornville | Ohio |
| United States | Martin Diagnostic Clinic | Tomball | Texas |
| United States | Omega Medical Research | Warwick | Rhode Island |
| United States | The Kaufmann Clinic, Inc. | Woodstock | Georgia |
| Lead Sponsor | Collaborator |
|---|---|
| BioCryst Pharmaceuticals |
United States, Australia, New Zealand, South Africa,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Subject's Severity of Illness (Score*Hours) | A subject's severity of illness (area under the symptom score curve, as measured in score-hours) was assessed using available symptom score data until the time of alleviation of symptoms.The score-hours were calculated as the product of the daily symptom score times the hours to alleviation. All available data until time of alleviation were utilized. The daily symptom score was defined as the sum of the 7 symptoms of influenza recorded by the subject in the diary each day (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]); for the composite score, individual scores were summed, with a range from 0 to 21. |
Information collected predose on Day 1 and then once daily through Day 14 | No |
| Other | Time to Resolution of Fever | Time to resolution of fever was defined as the number of hours from initiation of study drug until temperature was less than 37.2 °C (99.0 °F) and no antipyretic medication had been taken for at least 12 hours. | Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 | No |
| Other | Incidence of Influenza-related Complications | Study personnel were provided with an IRC checklist in the CRF to evaluate the subject for the presence of clinical signs and/or symptoms of the following IRCs: sinusitis, otitis, bronchitis, and pneumonia. Subjects with clinical signs and/or symptoms consistent with these conditions at Screening were not eligible for enrollment in this study. | 14 days | No |
| Other | Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50) | Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. | Baseline | No |
| Other | Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50) | Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype. | Baseline and up to 14 days | No |
| Other | Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50) | Baseline value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug. | Baseline and up to 14 days | No |
| Other | Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50) | Change from Baseline to last positive value of influenza virus susceptibility to neuraminidase inhibitors was assessed using virology laboratory tests. Virology laboratory tests included phenotypic characterizations of influenza virus recovered (hemagglutinin and neuraminidase) and viral susceptibility to zanamivir, oseltamivir, and peramivir, as well as genotyping of virus isolates. These analyses were presented separately by treatment group and viral subtype. Baseline was defined as the last non-missing value occuring prior to the initiation of study drug. | Baseline and up to 14 days | No |
| Primary | Time to Alleviation of Symptoms (Kaplan-Meier Estimate) | The primary efficacy endpoint was the time to alleviation of symptoms calculated as the number of hours from initiation of study drug until the start of the time period in which all 7 symptoms of influenza were either absent or present at a level no greater than mild for at least 21.5 (24 hours - 10%) hours. Subjects with missing diary data were excluded and those who did not experience alleviation of symptoms were censored at the last observed symptom assessment. | Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 | No |
| Secondary | Change in Influenza Virus Shedding | Changes from Baseline in log10 TCID50/mL through Days 3, 4, and 9 were presented by treatment group for subjects with positive viral titers at Baseline (log10 TCID50/mL >0.5). | Baseline and Days 3, 4, 9 | No |