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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00453999




Registration number
NCT00453999
Ethics application status
Date submitted
27/03/2007
Date registered
29/03/2007
Date last updated
12/02/2015

Titles & IDs
Public title
Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza
Scientific 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
Secondary ID [1] 0 0
BCX1812-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Peramivir 200 mg
Treatment: Drugs - Peramivir 400 mg
Treatment: Drugs - Oseltamivir

Experimental: Arm 1: Peramivir 200 mg - Peramivir 200 mg administered intravenously once daily for 5 days (5 doses)

Experimental: Arm 2: Peramivir 400 mg - Peramivir 400 mg administered intravenously once daily for 5 days (5 doses)

Experimental: Arm 3: Oseltamivir - Oseltamivir 75 mg oral suspension administered orally twice daily for 5 days (10 doses)


Treatment: Drugs: 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

Treatment: Drugs: 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)

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
14 days
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Days 2, 3, 4, 5, 10, and 14
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
14 days
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
14 days
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
14 days
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline, and 12, 24, 36, 48, 72, and 96 hours

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Prince Of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Westmead Hospital - Wentworthville
Recruitment hospital [3] 0 0
Cairns Base Hospital - Cairns
Recruitment hospital [4] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [5] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 0 0
Repatriation General Hospital - Daw Park
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Wentworthville
Recruitment postcode(s) [3] 0 0
4870 - Cairns
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
4215 - Southport
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
5041 - Daw Park
Recruitment postcode(s) [8] 0 0
3050 - Parkville
Recruitment postcode(s) [9] 0 0
6060 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Montana
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
Country [27] 0 0
Canada
State/province [27] 0 0
British Columbia
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Canada
State/province [30] 0 0
Saskatchewan
Country [31] 0 0
Hong Kong
State/province [31] 0 0
Hong Kong
Country [32] 0 0
Hong Kong
State/province [32] 0 0
Shatin - New Territories
Country [33] 0 0
New Zealand
State/province [33] 0 0
Christchurch
Country [34] 0 0
New Zealand
State/province [34] 0 0
Hamilton
Country [35] 0 0
New Zealand
State/province [35] 0 0
Tauranga
Country [36] 0 0
Singapore
State/province [36] 0 0
Singapore
Country [37] 0 0
South Africa
State/province [37] 0 0
E. Cape
Country [38] 0 0
South Africa
State/province [38] 0 0
Free State
Country [39] 0 0
South Africa
State/province [39] 0 0
Gauteng
Country [40] 0 0
South Africa
State/province [40] 0 0
KZ-Natal
Country [41] 0 0
South Africa
State/province [41] 0 0
Mpumalanga
Country [42] 0 0
South Africa
State/province [42] 0 0
W Cape
Country [43] 0 0
South Africa
State/province [43] 0 0
WC

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BioCryst Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00453999
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications