Clinical trial NCT00453999: Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza
Official title: Phase II, Multicenter, Randomized, Double-Mask, Double-Dummy Study Comparing Efficacy and Safety of Intravenous Peramivir Once Daily Versus Oral Oseltamivir Twice Daily in Adults With Acute Serious or Potentially Life-Threatening Influenza
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: influenza
flu
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-03-29
Enrollment: 137
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 study has been designed as a randomized, double-blind, controlled, study to evaluate the efficacy and safety of two once daily intravenous peramivir regimens (200 mg and 400 mg) versus oral oseltamivir phosphate (75 mg twice daily) in hospitalized subjects with acute serious or potentially life threatening influenza. Study treatments will be provided for up to 5 consecutive days.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years of age, male or female
* Able to provide informed consent, or for whom consent may be provided by guardian
* Presence of fever at time of screening of ≥38.0°C (≥ 100.0°F) taken orally, or ≥38.5°C (≥101.2°F) taken rectally. This requirement is waived if the subject has (1) a history of fever within 24 hours prior to screening and administered any antipyretic(s) in the 24 hours prior to screening, or (2) has no history of documented fever as defined above, but reports a symptom of feverishness at some time during 48 hours prior to screening
* Presence of at least 1 respiratory symptom (cough, sore throat, nasal congestion/symptoms) of any severity (mild, moderate, severe)
* Presence of at least 1 constitutional symptom (headache, myalgia, feverishness, malaise, fatigue) of any severity (mild, moderate, severe)
* Onset of illness no more than 72 hours before presentation. Time of onset of illness defined as either (1) the time when temperature (oral or rectal) was elevated (at least 1°C of elevation-oral temperature), OR (2) the time when the subject experienced the presence of at least 1 respiratory symptom AND the presence of at least 1 constitutional symptom
* Presence of 1 or more of the following factors in a subject willing to be hospitalized for inpatient observation and treatment:
* Age ≥60 years
* Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy
* History of congestive heart failure with or without medically significant recent change in cardiac status, but without signs or symptoms compatible with NYHA Class IV functional status
* Presence of diabetes mellitus, clinically stable or unstable
* Transcutaneous oxygen saturation \<94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value
* Systolic blood pressure \<90 mmHg
* Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care
* Positive rapid antigen test (RAT) for influenza A and/or influenza B (using an approved test kit) or other test for influenza virus antigen performed in a clinical laboratory at the screening/enrollment evaluation
* Females of childbearing potential must report one of the following:
* Be surgically sterile or clinically post-menopausal
* 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 for all perimenopausal women or women of child-bearing potential
* 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 for all perimenopausal women or women of child-bearing potential
* 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 for all perimenopausal women or women of child-bearing potential

Exclusion Criteria:

* Immunized against influenza with live attenuated virus vaccine in the previous weeks
* Treatment with any dose(s) of rimantadine, amantadine, zanamivir, or oseltamivir in the previous 7 days
* Current clinical evidence of a recognized or suspected acute non-influenzal infectious illness with onset prior to Screening
* Serum creatinine laboratory result at Screening \>1.6 mg/dL or a result \>25% above the upper limit of normal for the laboratory performing the test
* History of clinically significant proteinuria (≥1000 mg/24 hrs)
* History of moderate or severe renal impairment and/or previous clinical laboratory data indicating an estimated creatinine clearance \<50 mL/min during the previous 12 months
* Electrocardiogram (ECG) at Screening visit showing evidence of acute ischemia, or presence of a medically significant dysrhythmia
* Presence of cardiac signs or symptoms compatible with NYHA Class III or Class IV functional status for congestive heart failure or angina (see NYHA Appendix V)
* Presence of diagnosed COPD or other chronic lung condition requiring either continuous or intermittent oxygen therapy as an outpatient. Note: Subjects who are determined to require acute supplemental oxygen therapy at the time of Screening and/or at hospital admission may be enrolled, if exclusion criteria #13 or #14 are not applicable.
* History of organ transplantation during the previous 12 months
* Known HIV infection with most recent CD4+ T-cell count ≤350 cells/mL
* History of diagnosis of any type of cancer (hematologic or solid tumor), that has required chemotherapy or radiation therapy in the previous 12 months, excluding non-melanomatous localized skin cancer
* Presence of ongoing requirement for chronic mechanical ventilation, either via oral or nasotracheal intubation or via tracheostomy, or chronic or intermittent requirement for BiPAP (bilevel positive airway pressure) at screening. Note: Subjects who require intermittent CPAP treatment for sleep apnea (without oxygen supplementation) may be enrolled
* Subjects who require acute mechanical ventilatory support of any type at the time of screening.
* History of alcohol abuse or drug addiction during the previous 12 months
* Participation in a clinical study of an experimental medication or other treatment during the previous 4 weeks
* Previous treatment with intravenous or intramuscular peramivir
* Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding
* Subjects who have been hospitalized due to a condition other than acute influenza and in whom influenza is diagnosed during hospitalization.

Primary outcomes:
measure: Time to Clinical Stability (Kaplan-Meier Estimate)
timeFrame: 14 days
Secondary outcomes:
measure: Change From Baseline in Scores of Symptoms of Influenza
timeFrame: Baseline, Days 2, 3, 4, 5, 10, and 14
measure: Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate)
timeFrame: 14 days
measure: Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study)
timeFrame: 14 days
measure: Time to Hospital Discharge (Kaplan-Meier Estimate)
timeFrame: 14 days
measure: Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined)
timeFrame: Baseline, and 12, 24, 36, 48, 72, and 96 hours
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Pulmonary Associates of Mobile, P.C.
state: Alabama
city: Jonesboro
country: United States
facility: St. Bernards Research Center/Clopton Clinic
state: Arkansas
city: Orange
country: United States
facility: Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center, Department of Emergency Medicine
state: California
city: San Jose
country: United States
facility: Good Samaritan Hospital
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center, Clinical Research Unit
state: Colorado
city: Orlando
country: United States
facility: Orlando Regional Healthcare
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital, Department of Infectious Disease
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta, P.C.
state: Georgia
city: Savannah
country: United States
facility: St. Joseph's/Candler Health System, Inc.
state: Georgia
city: Idaho Falls
country: United States
facility: Idaho Falls Infectious Diseases, PLLC
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic, LLP
state: Illinois
city: Indianapolis
country: United States
facility: Wishard Hospital/Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Infectious Disease of Indiana, PSC
state: Indiana
city: Natchitoches
country: United States
facility: Natchitoches Internal Medicine
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center-Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: VA Maryland Health Care System
state: Maryland
city: Baltimore
country: United States
facility: Franklin Square Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital Troy
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group, PLLC
state: Montana
city: Hackensack
country: United States
facility: Hackensack University Medical Center, Department of Infectious Disease
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: Rochester General Hospital/University of Rochester
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Lowcountry Infectious Diseases, P.A.
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Salem
country: United States
facility: Veterans Affairs Medical Center
state: Virginia
city: Tacoma
country: United States
facility: Franciscan Health System
state: Washington
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Randwick
country: Australia
facility: Prince Of Wales Hospital
state: New South Wales
city: Wentworthville
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Cairns
country: Australia
facility: Cairns Base Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Daw Park
country: Australia
facility: Repatriation General Hospital
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-McMaster University Medical Centre
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton-L424
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital / Toronto Medical Laboratories
state: Ontario
city: Chicoutimi
country: Canada
facility: Center de Sante et des Services Sociaux de Chicoutimi
state: Quebec
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Rimouski
country: Canada
facility: Centre de sante et de services sociaux Rimouski-Neigette (CSSSRN)
state: Quebec
city: Saskatoon
country: Canada
facility: Division of Infectious Diseases
state: Saskatchewan
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec-Pavillon CHUL
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: United Christian Hospital
city: Shatin - New Territories
country: Hong Kong
facility: The Prince of Wales Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Port Elizabeth
country: South Africa
facility: Global Clinical Trial Center
state: E. Cape
city: Bloemfontein
country: South Africa
facility: Genclin Corporation
state: Free State
city: Benoni
country: South Africa
facility: Benmed / Pentagon Hospital
state: Gauteng
city: Cape Town
country: South Africa
facility: Private Practice
state: Gauteng
city: Johannesburg,
country: South Africa
facility: Newgate Centre
state: Gauteng
city: Krugersdorp
country: South Africa
facility: DJW Navorsing
state: Gauteng
city: Pretoria
country: South Africa
facility: Medforum Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Eugene Marais Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Global Clinical Trials (GCT)
state: Gauteng
city: Soweto
country: South Africa
facility: Dr Bhorat
state: Gauteng
city: Durban
country: South Africa
facility: Sebastian, P
state: KZ-Natal
city: Nelspruit
country: South Africa
facility: Eksteen, MC
state: Mpumalanga
city: Worcester
country: South Africa
facility: Dr. L.J. van Zyl
state: W Cape
city: Cape town
country: South Africa
facility: N1 City Hospital
state: WC
Study officials:
References:
citation: Ison MG, Hui DS, Clezy K, O'Neil BJ, Flynt A, Collis PJ, Simon TJ, Alexander WJ. A clinical trial of intravenous peramivir compared with oral oseltamivir for the treatment of seasonal influenza in hospitalized adults. Antivir Ther. 2013;18(5):651-61. doi: 10.3851/IMP2442. Epub 2012 Oct 30.