Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza

NCT ID: NCT00453999

Last Updated: 2015-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2009-08-31

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.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1: Peramivir 200 mg

Peramivir 200 mg administered intravenously once daily for 5 days (5 doses)

Group Type: EXPERIMENTAL

Peramivir 200 mg

Intervention Type: DRUG

Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment

Arm 2: Peramivir 400 mg

Peramivir 400 mg administered intravenously once daily for 5 days (5 doses)

Group Type: EXPERIMENTAL

Peramivir 400 mg

Intervention Type: DRUG

Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 ml)

Arm 3: Oseltamivir

Oseltamivir 75 mg oral suspension administered orally twice daily for 5 days (10 doses)

Group Type: EXPERIMENTAL

Oseltamivir

Intervention Type: DRUG

Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)

Interventions

Peramivir 200 mg

Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment

Intervention Type: DRUG

Peramivir 400 mg

Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 ml)

Intervention Type: DRUG

Oseltamivir

Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)

Intervention Type: DRUG

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)
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioCryst Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pulmonary Associates of Mobile, P.C.

Mobile, Alabama, United States

St. Bernards Research Center/Clopton Clinic

Jonesboro, Arkansas, United States

Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.

Orange, California, United States

University of California Irvine Medical Center

Orange, California, United States

University of California Davis Medical Center, Department of Emergency Medicine

Sacramento, California, United States

Good Samaritan Hospital

San Jose, California, United States

National Jewish Medical and Research Center, Clinical Research Unit

Denver, Colorado, United States

Orlando Regional Healthcare

Orlando, Florida, United States

James A. Haley Veterans Hospital, Department of Infectious Disease

Tampa, Florida, United States

Medical College of Georgia

Augusta, Georgia, United States

Infectious Disease Specialists of Atlanta, P.C.

Decatur, Georgia, United States

St. Joseph's/Candler Health System, Inc.

Savannah, Georgia, United States

Idaho Falls Infectious Diseases, PLLC

Idaho Falls, Idaho, United States

Northwestern University

Chicago, Illinois, United States

Springfield Clinic, LLP

Springfield, Illinois, United States

Wishard Hospital/Indiana University

Indianapolis, Indiana, United States

Infectious Disease of Indiana, PSC

Indianapolis, Indiana, United States

Natchitoches Internal Medicine

Natchitoches, Louisiana, United States

Louisiana State University Health Sciences Center-Shreveport

Shreveport, Louisiana, United States

VA Maryland Health Care System

Baltimore, Maryland, United States

Franklin Square Hospital

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Wayne State University School of Medicine

Detroit, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

William Beaumont Hospital Troy

Troy, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercury Street Medical Group, PLLC

Butte, Montana, United States

Hackensack University Medical Center, Department of Infectious Disease

Hackensack, New Jersey, United States

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

University of New Mexico

Albuquerque, New Mexico, United States

Rochester General Hospital/University of Rochester

Rochester, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Lowcountry Infectious Diseases, P.A.

Charleston, South Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

Veterans Affairs Medical Center

Salem, Virginia, United States

Franciscan Health System

Tacoma, Washington, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Prince Of Wales Hospital

Randwick, New South Wales, Australia

Westmead Hospital

Wentworthville, New South Wales, Australia

Cairns Base Hospital

Cairns, Queensland, Australia

Mater Adult Hospital

South Brisbane, Queensland, Australia

Gold Coast Hospital

Southport, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Repatriation General Hospital

Daw Park, South Australia, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Kelowna General Hospital

Kelowna, British Columbia, Canada

Hamilton Health Sciences-McMaster University Medical Centre

Hamilton, Ontario, Canada

St. Joseph's Healthcare Hamilton-L424

Hamilton, Ontario, Canada

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Mount Sinai Hospital / Toronto Medical Laboratories

Toronto, Ontario, Canada

Center de Sante et des Services Sociaux de Chicoutimi

Chicoutimi, Quebec, Canada

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Quebec-Pavillon CHUL

Québec, Quebec, Canada

Centre de sante et de services sociaux Rimouski-Neigette (CSSSRN)

Rimouski, Quebec, Canada

Division of Infectious Diseases

Saskatoon, Saskatchewan, Canada

Princess Margaret Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

United Christian Hospital

Hong Kong, , Hong Kong

The Prince of Wales Hospital

Shatin - New Territories, , Hong Kong

Christchurch Hospital

Christchurch, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Tauranga Hospital

Tauranga, , New Zealand

National University Hospital

Singapore, , Singapore

Tan Tock Seng Hospital

Singapore, , Singapore

Global Clinical Trial Center

Port Elizabeth, E. Cape, South Africa

Genclin Corporation

Bloemfontein, Free State, South Africa

Benmed / Pentagon Hospital

Benoni, Gauteng, South Africa

Private Practice

Cape Town, Gauteng, South Africa

Newgate Centre

Johannesburg, Gauteng, South Africa

DJW Navorsing

Krugersdorp, Gauteng, South Africa

Medforum Hospital

Pretoria, Gauteng, South Africa

Eugene Marais Hospital

Pretoria, Gauteng, South Africa

Global Clinical Trials (GCT)

Pretoria, Gauteng, South Africa

Dr Bhorat

Soweto, Gauteng, South Africa

Sebastian, P

Durban, KZ-Natal, South Africa

Eksteen, MC

Mbombela, Mpumalanga, South Africa

Dr. L.J. van Zyl

Worcester, W Cape, South Africa

N1 City Hospital

Cape Town, WC, South Africa

Countries

United States; Australia; Canada; Hong Kong; New Zealand; Singapore; South Africa

References

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.

Reference Type: DERIVED

PMID: 23111657 (View on PubMed)

Other Identifiers

BCX1812-201

Identifier Type: -

Identifier Source: org_study_id