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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00453999
• Other study ID #: BCX1812-201
• Status: Completed
• Phase: Phase 2
• First received: March 27, 2007
• Last updated: January 28, 2015
• Start date: July 2007
• Est. completion date: August 2009

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 CanadaAustralia: Human Research Ethics CommitteeHong Kong: Department of HealthNew Zealand: Institutional Review BoardSingapore: Health Sciences AuthoritySouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: August 2009
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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

Locations

Country	Name	City	State
Australia	Cairns Base Hospital	Cairns	Queensland
Australia	Repatriation General Hospital	Daw Park	South Australia
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Prince Of Wales Hospital	Randwick	New South Wales
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	Gold Coast Hospital	Southport	Queensland
Australia	Westmead Hospital	Wentworthville	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Center de Sante et des Services Sociaux de Chicoutimi	Chicoutimi	Quebec
Canada	Hamilton Health Sciences-McMaster University Medical Centre	Hamilton	Ontario
Canada	St. Joseph's Healthcare Hamilton-L424	Hamilton	Ontario
Canada	Kelowna General Hospital	Kelowna	British Columbia
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec-Pavillon CHUL	Quebec
Canada	Centre de sante et de services sociaux Rimouski-Neigette (CSSSRN)	Rimouski	Quebec
Canada	Division of Infectious Diseases	Saskatoon	Saskatchewan
Canada	Mount Sinai Hospital / Toronto Medical Laboratories	Toronto	Ontario
Hong Kong	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
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato Hospital	Hamilton
New Zealand	Tauranga Hospital	Tauranga
Singapore	National University Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
South Africa	Benmed / Pentagon Hospital	Benoni	Gauteng
South Africa	Genclin Corporation	Bloemfontein	Free State
South Africa	N1 City Hospital	Cape town	WC
South Africa	Private Practice	Cape Town	Gauteng
South Africa	Sebastian, P	Durban	KZ-Natal
South Africa	Newgate Centre	Johannesburg,	Gauteng
South Africa	DJW Navorsing	Krugersdorp	Gauteng
South Africa	Eksteen, MC	Nelspruit	Mpumalanga
South Africa	Global Clinical Trial Center	Port Elizabeth	E. Cape
South Africa	Eugene Marais Hospital	Pretoria	Gauteng
South Africa	Global Clinical Trials (GCT)	Pretoria	Gauteng
South Africa	Medforum Hospital	Pretoria	Gauteng
South Africa	Dr Bhorat	Soweto	Gauteng
South Africa	Dr. L.J. van Zyl	Worcester	W Cape
United States	University of New Mexico	Albuquerque	New Mexico
United States	Medical College of Georgia	Augusta	Georgia
United States	Franklin Square Hospital	Baltimore	Maryland
United States	VA Maryland Health Care System	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Mercury Street Medical Group, PLLC	Butte	Montana
United States	Lowcountry Infectious Diseases, P.A.	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Infectious Disease Specialists of Atlanta, P.C.	Decatur	Georgia
United States	National Jewish Medical and Research Center, Clinical Research Unit	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Wayne State University School of Medicine	Detroit	Michigan
United States	Hackensack University Medical Center, Department of Infectious Disease	Hackensack	New Jersey
United States	Baylor College of Medicine	Houston	Texas
United States	Idaho Falls Infectious Diseases, PLLC	Idaho Falls	Idaho
United States	Infectious Disease of Indiana, PSC	Indianapolis	Indiana
United States	Wishard Hospital/Indiana University	Indianapolis	Indiana
United States	St. Bernards Research Center/Clopton Clinic	Jonesboro	Arkansas
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Pulmonary Associates of Mobile, P.C.	Mobile	Alabama
United States	Natchitoches Internal Medicine	Natchitoches	Louisiana
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.	Orange	California
United States	University of California Irvine Medical Center	Orange	California
United States	Orlando Regional Healthcare	Orlando	Florida
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Rochester General Hospital/University of Rochester	Rochester	New York
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Medical Center, Department of Emergency Medicine	Sacramento	California
United States	Veterans Affairs Medical Center	Salem	Virginia
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Good Samaritan Hospital	San Jose	California
United States	St. Joseph's/Candler Health System, Inc.	Savannah	Georgia
United States	Louisiana State University Health Sciences Center-Shreveport	Shreveport	Louisiana
United States	Springfield Clinic, LLP	Springfield	Illinois
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Franciscan Health System	Tacoma	Washington
United States	James A. Haley Veterans Hospital, Department of Infectious Disease	Tampa	Florida
United States	William Beaumont Hospital Troy	Troy	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Clinical Stability (Kaplan-Meier Estimate)	Time to clinical stability was summarized overall and for individual clinical signs for each treatment group using the method of Kaplan Meier. Subjects who did not experience clinical stability were censored at the date of their last non-missing assessment during the study (whether this assessment occurred as an inpatient or as an outpatient).	14 days	No
Secondary	Change From Baseline in Scores of Symptoms of Influenza	Descriptive statistics for the change from baseline in each of the 7 symptoms of influenza (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]) were tabulated by treatment group. Missing data were excluded.	Baseline, Days 2, 3, 4, 5, 10, and 14	No
Secondary	Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate)	Changes in each subject's ability to perform usual activities as determined from the visual analog scale (0 to 10, where 0 indicated subject was unable to perform usual activities at all and 10 indicated subject was able to perform all usual activities fully) were summarized by study visit and treatment group. The time to resumption of a subject's ability to perform usual activities was estimated using the method of Kaplan Meier. Subjects who did not return to the pre-study level of performance of usual activities were censored at the time of their last assessment. (Note: N is the number of ITTI participants with available data).	14 days	No
Secondary	Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study)	The number of subjects with clinical relapse, defined as changes in 2 or more signs of clinical stability to values outside the range of normalization criteria for a duration of at least 12 consecutive hours after clinical stability had been attained, were summarized by treatment group.	14 days	No
Secondary	Time to Hospital Discharge (Kaplan-Meier Estimate)	Time to discharge from hospital was estimated using the method of Kaplan Meier. Subjects who were not discharged from the hospital were censored at the time of their last assessment.	14 days	No
Secondary	Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined)	Reduction in viral shedding, assessed as the change in quantitative viral titers and defined as the time-weighted change from baseline in TCID50/mL, was summarized for each treatment group.	Baseline, and 12, 24, 36, 48, 72, and 96 hours	No