Safety Study of IV Peramivir in Hospitalized Subjects With Confirmed or Suspected Influenza

• Sponsor: BioCryst Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00957996
• Collaborator: Department of Health and Human Services (U.S. Fed)
• Enrollment: 234
• Locations: 110
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 3, open-label, randomized study of the antiviral activity, safety, and tolerability of intravenous Peramivir in hospitalized subjects with confirmed or suspected influenza infection.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Influenza; Cough; Sore Throat; Nasal Congestion; Myalgia; Headache; Fatigue	Drug: Peramivir; Drug: Peramivir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-Label, Randomized Study of the Antiviral Activity, Safety, and Tolerability of Intravenous Peramivir in Hospitalized Subjects With Confirmed or Suspected Influenza Infection
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peramivir 300 mg Peramivir 300 mg twice daily	Drug: Peramivir; 300 mg twice daily
Experimental: Peramivir 600 mg Peramivir 600 mg once daily	Drug: Peramivir; 600 mg once daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Influenza Virus Titer (48 Hours) [Baseline and 48 hours]

   The time-weighted change from baseline in log10 tissue culture infective dose50 (TCID50/mL) was calculated on a by-subject basis through 48 hours using the trapezoidal rule with all available data minus the baseline value. Ninety-five percent confidence intervals about the median time-weighted change from baseline were presented for each treatment group.

Secondary Outcome Measures

1. Change in Influenza Virus Titer, as Measured by Quantitative RT-PCR (log10 vp/mL) [Baseline, 48, 108, 216 hours]

   The time-weighted change from baseline in viral titer measured by RT-PCR was calculated on a by-subject basis through 216 hours using the trapezoidal rule with all available data minus the baseline value. Ninety-five percent confidence intervals about the median time-weighted change from baseline were presented for each treatment group.

2. Time to Clinical Resolution [28 days]

   Time to clinical resolution was the number of hours from initiation of study treatment until 4 of the 5 signs of clinical stability (including both body temperature and transcutaneous oxygen saturation) met resolution criteria that was maintained for at least 24 hours. The median time to clinical resolution and associated 95% confidence interval were estimated for each treatment group using the method of Kaplan-Meier. Subjects who did not achieve clinical resolution were censored at the time of their last assessment.

3. Number of Participants With Clinical Resolution [28 days]

   Clinical resolution was defined as normalization of at least 4 of the 5 signs of clinical stability (including both body temperature and transcutaneous oxygen saturation) for at least 24 hours.

4. Time to Alleviation of Symptoms [28 days]

   Time to alleviation of symptoms, defined as the time from initiation of study drug until the start of the 24 hour period where all seven symptoms of influenza are recorded as none or mild, was estimated using the method of Kaplan-Meier (adolescents and adults). The 95% confidence interval about the median was presented. Subjects who did not experience alleviation of symptoms were censored at the time of the last non-missing symptom assessment.

5. Time to Resolution of Fever [28 days]

   Time to resolution of fever was the number of hours from initiation of study treatment until temperature was ≤37.2°C/≤99°F oral or ≤37.8°C/≤100°F rectal or tympanic for at least 24 hours with no antipyretic medication taken within 4 hours prior to the temperature measurement. Subjects who did not achieve resolution of fever were censored at the time of their last assessment. The 95% confidence interval about the median were presented.

6. Time to Resumption of Usual Activities [28 days]

   Subject's ability to perform usual activities as determined from the visual analog scale (scale ranges from 0 to 10 where 0 indicates subject was unable to perform usual activities at all and 10 indicates subject is able to perform all usual activities fully) was summarized by study visit day and treatment group. The median time to resumption of usual daily activities and associated 95% CI was estimated using the method of Kaplan-Meier for adults and adolescents. Subjects who did not return to the pre-study level of performance of usual daily activities were censored at the time of their last non-missing visual analog scale value. A separate analysis was conducted for children.

7. Time to Hospital Discharge [28 days]

   Time to hospital discharge, defined as the number of days from initiation of study drug until the subject is discharged from the hospital, was estimated using the method of Kaplan-Meier. The 95% confidence interval about the median was presented. Subjects who were not discharged during the study period were censored at the last study visit. Subjects who died prior to discharge were censored at the longest observed time to discharge.

8. Number of Participants Experiencing Influenza-related Complications [28 days]

   Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis and pneumonia as reported on the Influenza-related complications CRF.

9. Number of Participants Admitted to ICU After Initiation of Treatment [28 days]

   The number of subjects experiencing ICU admission after initiation of treatment.

10. Duration of Postbaseline ICU Admission (Kaplan-Meier Estimate) [28 days]

    The duration of ICU admission after initiation of treatment was estimated by the method of Kaplan-Meier. Subjects who were not discharged from the ICU were censored at the time of their last assessment

11. Survival (Kaplan-Meier Estimates) [14 and 28 days]

    Survival was calculated as the number of days from initiation of study drug until death or last contact. Overall survival was estimated by the method of Kaplan-Meier; 95% confidence intervals for 14- and 28-day survival were presented by treatment group. Subjects who had not died were censored at the date of last contact.

Other Outcome Measures

1. Number of Participants Who Required More Than 5 Days of Peramivir Treatment [28 days]

   The number of subjects who continued more than 5 days were as reported on the Continuation of Treatment CRF page.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and non-pregnant female subjects 6 years of age or older.

• Able to provide written informed consent, or for whom written consent may be provided by a parent guardian or legally authorized representative, unless consent provided by a parent, guardian or legally authorized representative is not consistent with applicable local or ethical procedures, directives and /or guidelines.

• Presence of clinical signs and/or symptoms consistent with an acute illness compatible with influenza infection; a measured temperature of ≥ 38.0°C (100.4°F) oral, or ≥ 38.6°C (101.4°F) rectal or tympanic and recent onset of at least one of the following: rhinorrhea or nasal congestion, sore throat or cough. Measured temperature can include fever meeting the above criteria as reported by the subject or their parent, guardian or legally authorized representative in the 24 hours prior to Screening. The requirement for fever is waived for any subject with influenza infection already confirmed by laboratory tests (including Rapid Antigen Tests).

• Confirmation of influenza A or B infection in the local community by one of the following means:

• the institution's local laboratory,

• the local public health system

• the national public health system

• a laboratory of a recognized national or multinational influenza surveillance scheme.

• Severity of illness requiring or anticipated to require in-hospital care.

Exclusion Criteria:

• Subjects who have been hospitalized for greater than 24 hours (not including time spent in the emergency department).Blood platelet count of < 20 x 109/L.

• Serum bilirubin > 6 mg/dL at time of Screening evaluation.

• Serum ALT or AST > 5 X upper limit of normal at time of Screening evaluation.

• Serum creatinine > 5.0 mg/dL at time of Screening evaluation.

• Subjects who require peritoneal dialysis or hemofiltration.

• Altered neurologic status as defined by a Glasgow Coma Score of ≤ 9, unless medically induced.

• Females who are pregnant (positive urine or serum pregnancy test at Screening evaluation) or breastfeeding.

• Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy. (Subjects who have completed treatment 30 days prior to enrollment are allowed to enroll in the study. Hormone treatment for cancer is also acceptable).

• Prior hematopoietic stem cell transplantation or solid organ transplant during the previous 4 months.

• HIV infection with a known CD4 count < 200 cells/ mm3 unless on a stable highly active antiretroviral (HAART) regimen for at least 6 months.

• Presence of a preexisting chronic infection that is undergoing or requiring medical therapy (eg, tuberculosis). (Subjects with chronic osteomyelitis or hepatitis B or C not requiring treatment are not excluded).

• Presence of any preexisting illness that, in the opinion of the Investigator, would place the subject at an unreasonably increased risk through participation in this study.

• Participation as a subject in any study of an experimental treatment for any condition within the 30 days prior to the time of the Screening evaluation.

• Subjects diagnosed with cystic fibrosis.

• Subjects with confirmed clinical evidence of acute non-influenzal infection at the time of Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Dothan	Alabama	United States
2		Mobile	Alabama	United States
3		Jonesboro	Arkansas	United States
4		Little Rock	Arkansas	United States
5		Fountain Valley	California	United States
6		Harbor City	California	United States
7		La Mesa	California	United States
8		Long Beach	California	United States
9		Los Angeles	California	United States
10		Modesto	California	United States
11		Oceanside	California	United States
12		Orange	California	United States
13		Palo Alto	California	United States
14		Sacramento	California	United States
15		San Diego	California	United States
16		San Francisco	California	United States
17		San Jose	California	United States
18		Denver	Colorado	United States
19		Wheat Ridge	Colorado	United States
20		Washington	District of Columbia	United States
21		Brandon	Florida	United States
22		Ft. Lauderdale	Florida	United States
23		Gainsville	Florida	United States
24		Ocoee	Florida	United States
25		Orlando	Florida	United States
26		West Palm Beach	Florida	United States
27		Columbus	Georgia	United States
28		Decatur	Georgia	United States
29		Honolulu	Hawaii	United States
30		Idaho Falls	Idaho	United States
31		Chicago	Illinois	United States
32		Rock Island	Illinois	United States
33		Springfield	Illinois	United States
34		Indianapolis	Indiana	United States
35		South Bend	Indiana	United States
36		Topeka	Kansas	United States
37		Hazard	Kentucky	United States
38		Natchitoches	Louisiana	United States
39		Shreveport	Louisiana	United States
40		Baltimore	Maryland	United States
41		Boston	Massachusetts	United States
42		Detroit	Michigan	United States
43		Royal Oak	Michigan	United States
44		Troy	Michigan	United States
45		Minneapolis	Minnesota	United States
46		St. Louis	Missouri	United States
47		Butte	Montana	United States
48		Omaha	Nebraska	United States
49		Englewood	New Jersey	United States
50		Hackensack	New Jersey	United States
51		Neptune	New Jersey	United States
52		New Brunswick	New Jersey	United States
53		Somers Point	New Jersey	United States
54		Albuquerque	New Mexico	United States
55		Albany	New York	United States
56		Bronx	New York	United States
57		Brooklyn	New York	United States
58		Buffalo	New York	United States
59		Jamaica	New York	United States
60		New York	New York	United States
61		Valhalla	New York	United States
62		Akron	Ohio	United States
63		Cleveland	Ohio	United States
64		Lima	Ohio	United States
65		Toledo	Ohio	United States
66		Portland	Oregon	United States
67		Philadelphia	Pennsylvania	United States
68		Providence	Rhode Island	United States
69		Charleston	South Carolina	United States
70		Sioux Falls	South Dakota	United States
71		Houston	Texas	United States
72		San Antonio	Texas	United States
73		Tomball	Texas	United States
74		Salt Lake City	Utah	United States
75		Norfolk	Virginia	United States
76		Salem	Virginia	United States
77		Bellevue	Washington	United States
78		Seattle	Washington	United States
79		Milwaukee	Wisconsin	United States
80		Brisbane	Queensland	Australia
81		Cairns	Queensland	Australia
82		Southport	Queensland	Australia
83		Clayton	Victoria	Australia
84		Melbourne	Victoria	Australia
85		Parkville	Victoria	Australia
86		Kelowna	British Columbia	Canada
87		Winnipeg	Manitoba	Canada
88		Hamilton	Ontario	Canada
89		Kingston	Ontario	Canada
90		Ottawa	Ontario	Canada
91		Toronto	Ontario	Canada
92		Chicoutimi	Quebec	Canada
93		Montréal	Quebec	Canada
94		Sainte-Foy	Quebec	Canada
95		Sherbrooke	Quebec	Canada
96		Trois-Rivieres	Quebec	Canada
97		Saskatoon	Saskatchewan	Canada
98		Edmonton		Canada
99		Aguascalientes	AGS	Mexico
100		Distrito Federal	DF	Mexico
101		Guadalajara	JAL	Mexico
102		Zapopan	JAL	Mexico
103		Monterrey	NL	Mexico
104		San Luis Potosi	SLP	Mexico
105		Durango		Mexico
106		Auckland	Wellington	New Zealand
107		Christchurch		New Zealand
108		Hamilton		New Zealand
109		Tauranga		New Zealand
110		San Juan		Puerto Rico

Sponsors and Collaborators

• BioCryst Pharmaceuticals
• Department of Health and Human Services

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00957996
• Other Study ID Numbers: BCX1812-303; HHS 0100200700032C
• First Posted: Aug 13, 2009
• Last Update Posted: Feb 12, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by BioCryst Pharmaceuticals: influenza; hospitalized; flu; antiviral
• Additional relevant MeSH terms: Influenza, Human; Pharyngitis; Myalgia; Headache; Peramivir

Study Results

Participant Flow

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Period Title: Overall Study
STARTED	117	117
COMPLETED	91	89
NOT COMPLETED	26	28

Baseline Characteristics

Arm/Group Title	Peramivir 300mg	Peramivir 600mg	Total
Arm/Group Description	300 mg twice daily Peramivir: 300 mg twice daily	600 mg once daily Peramivir: 600 mg once daily	Total of all reporting groups
Overall Participants	117	117	234
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	48.3	48.4	48.3
Age, Customized (participants) [Number]
Children 6-11 years	0 0%	0 0%	0 0%
Adolescents 12-17 years	3 2.6%	1 0.9%	4 1.7%
Adults 18-24 years	4 3.4%	8 6.8%	12 5.1%
Adults 25-34 years	17 14.5%	19 16.2%	36 15.4%
Adults 35-44 years	29 24.8%	18 15.4%	47 20.1%
Adults 45-54 years	26 22.2%	29 24.8%	55 23.5%
Adults 55-64 years	18 15.4%	27 23.1%	45 19.2%
Adults 65-74 years	11 9.4%	10 8.5%	21 9%
Adults ≥75 years	9 7.7%	5 4.3%	14 6%
Sex: Female, Male (Count of Participants)
Female	74 63.2%	65 55.6%	139 59.4%
Male	43 36.8%	52 44.4%	95 40.6%
Race/Ethnicity, Customized (participants) [Number]
White	78 66.7%	84 71.8%	162 69.2%
Black, of African Heritage or African American	16 13.7%	13 11.1%	29 12.4%
Other	15 12.8%	11 9.4%	26 11.1%
Asian	5 4.3%	5 4.3%	10 4.3%
American Indian or Alaska Native	3 2.6%	1 0.9%	4 1.7%
Native Hawaiian or other Pacific Islander	0 0%	3 2.6%	3 1.3%
Body mass index (BMI) (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	32	31	31
Smoking status (participants) [Number]
Current smoker	43 36.8%	45 38.5%	88 37.6%
Not current smoker	73 62.4%	72 61.5%	145 62%
Missing	1 0.9%	0 0%	1 0.4%
Influenza vaccination status (participants) [Number]
Not vaccinated this year	74 63.2%	81 69.2%	155 66.2%
Vaccinated this year	41 35%	36 30.8%	77 32.9%
Missing	2 1.7%	0 0%	2 0.9%
Number of subjects with ICU admission at Baseline (participants) [Number]
Number [participants]	18 15.4%	21 17.9%	39 16.7%
APACHE II Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	14 (7.5)	17 (5.4)	15 (6.6)
Chest X-ray at Screening (participants) [Number]
Normal	82 70.1%	86 73.5%	168 71.8%
Abnormal	31 26.5%	28 23.9%	59 25.2%
Missing	4 3.4%	3 2.6%	7 3%
Duration of illness (participants) [Number]
≤48 hours	18 15.4%	16 13.7%	34 14.5%
>48 hours	99 84.6%	101 86.3%	200 85.5%
Hemisphere of enrollment (participants) [Number]
Northern Hemisphere 09-10	107 91.5%	108 92.3%	215 91.9%
Southern Hemisphere 10	10 8.5%	9 7.7%	19 8.1%
Moderate renal impairment (participants) [Number]
Impaired	10 8.5%	11 9.4%	21 9%
Not impaired	103 88%	105 89.7%	208 88.9%
Missing	4 3.4%	1 0.9%	5 2.1%
Screening serum albumin (participants) [Number]
Grade 3	6 5.1%	8 6.8%	14 6%
Other Grade	105 89.7%	103 88%	208 88.9%
Missing	6 5.1%	6 5.1%	12 5.1%
Screening lymphocytes (participants) [Number]
Grade 3/4	15 12.8%	22 18.8%	37 15.8%
Other Grade	89 76.1%	89 76.1%	178 76.1%
Missing	13 11.1%	6 5.1%	19 8.1%
Screening neutrophils (participants) [Number]
Grade 3/4	0 0%	3 2.6%	3 1.3%
Other Grade	104 88.9%	108 92.3%	212 90.6%
Missing	13 11.1%	6 5.1%	19 8.1%
Supplemental oxygen required at Screening (participants) [Number]
Yes	75 64.1%	83 70.9%	158 67.5%
No	41 35%	32 27.4%	73 31.2%
Missing	1 0.9%	2 1.7%	3 1.3%
Subjects who received antivirals prior to treatment (participants) [Number]
Number [participants]	88 75.2%	82 70.1%	170 72.6%
Duration of hospital admission prior to first dose (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	1.1 (0.98)	1.3 (2.86)	1.2 (2.13)
Corticosteroid at enrollment (participants) [Number]
Yes	52 44.4%	68 58.1%	120 51.3%
No	65 55.6%	49 41.9%	114 48.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Influenza Virus Titer (48 Hours)
Description	The time-weighted change from baseline in log10 tissue culture infective dose50 (TCID50/mL) was calculated on a by-subject basis through 48 hours using the trapezoidal rule with all available data minus the baseline value. Ninety-five percent confidence intervals about the median time-weighted change from baseline were presented for each treatment group.
Time Frame	Baseline and 48 hours

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology. Overall, 83 subjects were excluded due to negative Baseline titers (log10 TCID50 0.5).

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	300 mg twice daily Peramivir: 300 mg twice daily	600 mg once daily Peramivir: 600 mg once daily
Measure Participants	20	24
Median (95% Confidence Interval) [log10 TCID50/mL]	-1.66	-1.47

2. Secondary Outcome

Title	Change in Influenza Virus Titer, as Measured by Quantitative RT-PCR (log10 vp/mL)
Description	The time-weighted change from baseline in viral titer measured by RT-PCR was calculated on a by-subject basis through 216 hours using the trapezoidal rule with all available data minus the baseline value. Ninety-five percent confidence intervals about the median time-weighted change from baseline were presented for each treatment group.
Time Frame	Baseline, 48, 108, 216 hours

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology. Overall, 41 subjects were excluded due to negative Baseline titers (viral particles/mL RT-PCR value 1.58 for Influenza A and 1.49 for Influenza B).

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	37	49
Change from baseline, 48 hours	-1.00	-1.07
Change from baseline, 108 hours	-1.65	-1.59
Change from baseline, 216 hours	-2.15	-1.79

3. Secondary Outcome

Title	Time to Clinical Resolution
Description	Time to clinical resolution was the number of hours from initiation of study treatment until 4 of the 5 signs of clinical stability (including both body temperature and transcutaneous oxygen saturation) met resolution criteria that was maintained for at least 24 hours. The median time to clinical resolution and associated 95% confidence interval were estimated for each treatment group using the method of Kaplan-Meier. Subjects who did not achieve clinical resolution were censored at the time of their last assessment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	56	70
Median (95% Confidence Interval) [hours]	44.7	166.1

4. Secondary Outcome

Title	Number of Participants With Clinical Resolution
Description	Clinical resolution was defined as normalization of at least 4 of the 5 signs of clinical stability (including both body temperature and transcutaneous oxygen saturation) for at least 24 hours.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	300 mg twice daily Peramivir: 300 mg twice daily	600 mg once daily Peramivir: 600 mg once daily
Measure Participants	57	70
Number [participants]	41 35%	42 35.9%

5. Secondary Outcome

Title	Time to Alleviation of Symptoms
Description	Time to alleviation of symptoms, defined as the time from initiation of study drug until the start of the 24 hour period where all seven symptoms of influenza are recorded as none or mild, was estimated using the method of Kaplan-Meier (adolescents and adults). The 95% confidence interval about the median was presented. Subjects who did not experience alleviation of symptoms were censored at the time of the last non-missing symptom assessment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology. Symptom data for 18 subjects was missing.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	51	58
Median (95% Confidence Interval) [hours]	135	158

6. Secondary Outcome

Title	Time to Resolution of Fever
Description	Time to resolution of fever was the number of hours from initiation of study treatment until temperature was ≤37.2°C/≤99°F oral or ≤37.8°C/≤100°F rectal or tympanic for at least 24 hours with no antipyretic medication taken within 4 hours prior to the temperature measurement. Subjects who did not achieve resolution of fever were censored at the time of their last assessment. The 95% confidence interval about the median were presented.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	57	70
Median (95% Confidence Interval) [hours]	27.2	24.2

7. Secondary Outcome

Title	Time to Resumption of Usual Activities
Description	Subject's ability to perform usual activities as determined from the visual analog scale (scale ranges from 0 to 10 where 0 indicates subject was unable to perform usual activities at all and 10 indicates subject is able to perform all usual activities fully) was summarized by study visit day and treatment group. The median time to resumption of usual daily activities and associated 95% CI was estimated using the method of Kaplan-Meier for adults and adolescents. Subjects who did not return to the pre-study level of performance of usual daily activities were censored at the time of their last non-missing visual analog scale value. A separate analysis was conducted for children.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	53	59
Median (95% Confidence Interval) [hours]	27.7	24.9

8. Secondary Outcome

Title	Time to Hospital Discharge
Description	Time to hospital discharge, defined as the number of days from initiation of study drug until the subject is discharged from the hospital, was estimated using the method of Kaplan-Meier. The 95% confidence interval about the median was presented. Subjects who were not discharged during the study period were censored at the last study visit. Subjects who died prior to discharge were censored at the longest observed time to discharge.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	57	70
Median (95% Confidence Interval) [days]	6	6

9. Secondary Outcome

Title	Number of Participants Experiencing Influenza-related Complications
Description	Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis and pneumonia as reported on the Influenza-related complications CRF.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	57	70
Number [participants]	39 33.3%	48 41%

10. Secondary Outcome

Title	Number of Participants Admitted to ICU After Initiation of Treatment
Description	The number of subjects experiencing ICU admission after initiation of treatment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	57	70
Number [participants]	2 1.7%	6 5.1%

11. Secondary Outcome

Title	Duration of Postbaseline ICU Admission (Kaplan-Meier Estimate)
Description	The duration of ICU admission after initiation of treatment was estimated by the method of Kaplan-Meier. Subjects who were not discharged from the ICU were censored at the time of their last assessment
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	57	70
Median (95% Confidence Interval) [days]	7	7

12. Other Pre-specified Outcome

Title	Number of Participants Who Required More Than 5 Days of Peramivir Treatment
Description	The number of subjects who continued more than 5 days were as reported on the Continuation of Treatment CRF page.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	300 mg twice daily Peramivir: 300 mg twice daily	600 mg once daily Peramivir: 600 mg once daily
Measure Participants	57	70
Number [participants]	16 13.7%	28 23.9%

13. Secondary Outcome

Title	Survival (Kaplan-Meier Estimates)
Description	Survival was calculated as the number of days from initiation of study drug until death or last contact. Overall survival was estimated by the method of Kaplan-Meier; 95% confidence intervals for 14- and 28-day survival were presented by treatment group. Subjects who had not died were censored at the date of last contact.
Time Frame	14 and 28 days

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat Infected (ITTI) population included all randomized subjects who received at least 1 dose/infusion of study drug, and had confirmed influenza A or B by culture, PCR, or serology.

Arm/Group Title	Peramivir 300 mg	Peramivir 600 mg
Arm/Group Description	Peramivir 300 mg twice daily	Peramivir 600 mg once daily
Measure Participants	57	70
14 Day Survival	98	93
28 Day Survival	94	86

Adverse Events

Time Frame	Reports of AEs were collected from the time of study drug administration through the follow-up period ending on Day 14 or Day 28.
Adverse Event Reporting Description	For subjects who experienced the same coded event more than once, only one event is presented. Four of 234 randomized subjects did not receive treatment; safety analyses included 230 subjects (114 in the Peramivir 300 mg arm and 116 in the Peramivir 600 mg arm).
Arm/Group Title	Peramivir 300 mg		Peramivir 600 mg
Arm/Group Description	300 mg twice daily Peramivir: 300 mg twice daily		600 mg once daily Peramivir: 600 mg once daily
All Cause Mortality
	Peramivir 300 mg		Peramivir 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Peramivir 300 mg		Peramivir 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/114 (18.4%)		26/116 (22.4%)
Blood and lymphatic system disorders
Thrombocytopenia	1/114 (0.9%)		0/116 (0%)
Cardiac disorders
Acute myocardial infarction	1/114 (0.9%)		0/116 (0%)
Atrial fibrillation	0/114 (0%)		1/116 (0.9%)
Bradycardia	0/114 (0%)		1/116 (0.9%)
Cardiac arrest	0/114 (0%)		1/116 (0.9%)
Cardiac failure	0/114 (0%)		1/116 (0.9%)
Cardiac failure congestive	0/114 (0%)		1/116 (0.9%)
Ventricular fibrillation	0/114 (0%)		1/116 (0.9%)
Congenital, familial and genetic disorders
Cystic fibrosis	0/114 (0%)		1/116 (0.9%)
Ear and labyrinth disorders
Vertigo	0/114 (0%)		1/116 (0.9%)
Gastrointestinal disorders
Colitis	0/114 (0%)		1/116 (0.9%)
Diarrhoea	1/114 (0.9%)		0/116 (0%)
Retroperitoneal haemorrhage	0/114 (0%)		1/116 (0.9%)
General disorders
Multi-organ failure	0/114 (0%)		1/116 (0.9%)
Non-cardiac chest pain	0/114 (0%)		1/116 (0.9%)
Infections and infestations
Septic shock	1/114 (0.9%)		3/116 (2.6%)
Sepsis	1/114 (0.9%)		2/116 (1.7%)
Pneumonia bacterial	2/114 (1.8%)		0/116 (0%)
Pneumonia staphylococcal	2/114 (1.8%)		0/116 (0%)
Pneumonia	1/114 (0.9%)		1/116 (0.9%)
Bronchiolitis	1/114 (0.9%)		0/116 (0%)
HIV Infection	1/114 (0.9%)		0/116 (0%)
Lower Respiratory Tract Infection	1/114 (0.9%)		0/116 (0%)
Meningococcal Bacteraemia	1/114 (0.9%)		0/116 (0%)
Pneumonia Necrotising	0/114 (0%)		1/116 (0.9%)
Pseudomonal Bacteraemia	0/114 (0%)		1/116 (0.9%)
Injury, poisoning and procedural complications
Accidental overdose	0/114 (0%)		1/116 (0.9%)
Overdose	1/114 (0.9%)		0/116 (0%)
Investigations
Alanine aminotransferase increased	1/114 (0.9%)		0/116 (0%)
Aspartate aminotransferase increased	1/114 (0.9%)		0/116 (0%)
Hepatic enzyme increased	0/114 (0%)		1/116 (0.9%)
Metabolism and nutrition disorders
Hyperkalaemia	0/114 (0%)		1/116 (0.9%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/114 (0%)		2/116 (1.7%)
Pain in extremity	1/114 (0.9%)		0/116 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma stage IV	0/114 (0%)		1/116 (0.9%)
Nervous system disorders
Cerebrovascular accident	0/114 (0%)		2/116 (1.7%)
Psychiatric disorders
Mental status changes	1/114 (0.9%)		0/116 (0%)
Renal and urinary disorders
Renal failure acute	1/114 (0.9%)		3/116 (2.6%)
Renal failure	0/114 (0%)		1/116 (0.9%)
Urinary retention	0/114 (0%)		1/116 (0.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	3/114 (2.6%)		3/116 (2.6%)
Acute respiratory distress syndrome	1/114 (0.9%)		3/116 (2.6%)
Chronic obstructive pulmonary disease	2/114 (1.8%)		1/116 (0.9%)
Pneumonia aspiration	0/114 (0%)		2/116 (1.7%)
Acute respiratory failure	1/114 (0.9%)		1/116 (0.9%)
Respiratory distress	1/114 (0.9%)		1/116 (0.9%)
Interstitial lung disease	1/114 (0.9%)		0/116 (0%)
Lung infiltration	1/114 (0.9%)		0/116 (0%)
Pulmonary embolism	0/114 (0%)		1/116 (0.9%)
Pulmonary haemorrhage	0/114 (0%)		1/116 (0.9%)
Skin and subcutaneous tissue disorders
Purpura	1/114 (0.9%)		0/116 (0%)
Vascular disorders
Hypertension	0/114 (0%)		1/116 (0.9%)
Hypertensive crisis	0/114 (0%)		1/116 (0.9%)
Hypoperfusion	0/114 (0%)		1/116 (0.9%)
Hypotension	0/114 (0%)		1/116 (0.9%)
Other (Not Including Serious) Adverse Events
	Peramivir 300 mg		Peramivir 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/114 (60.5%)		65/116 (56%)
Blood and lymphatic system disorders
Anaemia	5/114 (4.4%)		13/116 (11.2%)
Leukocytosis	4/114 (3.5%)		4/116 (3.4%)
Thrombocytosis	1/114 (0.9%)		4/116 (3.4%)
Cardiac disorders
Atrial Fibrillation	3/114 (2.6%)		2/116 (1.7%)
Cardiac Failure Congestive	2/114 (1.8%)		3/116 (2.6%)
Gastrointestinal disorders
Constipation	19/114 (16.7%)		11/116 (9.5%)
Diarrhoea	12/114 (10.5%)		16/116 (13.8%)
Nausea	10/114 (8.8%)		8/116 (6.9%)
Vomiting	4/114 (3.5%)		4/116 (3.4%)
Abdominal Distension	0/114 (0%)		5/116 (4.3%)
Gastrointestinal Sounds Abnormal	0/114 (0%)		3/116 (2.6%)
General disorders
Oedema Peripheral	10/114 (8.8%)		8/116 (6.9%)
Oedema	2/114 (1.8%)		6/116 (5.2%)
Generalised Oedema	3/114 (2.6%)		2/116 (1.7%)
Pain	3/114 (2.6%)		1/116 (0.9%)
Catheter Related Complication	3/114 (2.6%)		0/116 (0%)
Infections and infestations
Urinary Tract Infection	5/114 (4.4%)		2/116 (1.7%)
Fungal Skin Infection	3/114 (2.6%)		2/116 (1.7%)
Oral Herpes	3/114 (2.6%)		2/116 (1.7%)
Investigations
Alanine Aminotransferase Increased	4/114 (3.5%)		2/116 (1.7%)
Blood Triglycerides Increased	2/114 (1.8%)		4/116 (3.4%)
Aspartate Aminotransferase Increased	3/114 (2.6%)		2/116 (1.7%)
Blood Potassium Decreased	4/114 (3.5%)		1/116 (0.9%)
Metabolism and nutrition disorders
Hypokalaemia	8/114 (7%)		14/116 (12.1%)
Hyperglycaemia	7/114 (6.1%)		7/116 (6%)
Hypophosphataemia	5/114 (4.4%)		4/116 (3.4%)
Fluid Overload	3/114 (2.6%)		4/116 (3.4%)
Hypocalcaemia	4/114 (3.5%)		3/116 (2.6%)
Hypomagnesaemia	3/114 (2.6%)		4/116 (3.4%)
Metabolic Alkalosis	2/114 (1.8%)		5/116 (4.3%)
Hyperkalaemia	3/114 (2.6%)		3/116 (2.6%)
Hypoalbuminaemia	1/114 (0.9%)		3/116 (2.6%)
Musculoskeletal and connective tissue disorders
Back Pain	2/114 (1.8%)		3/116 (2.6%)
Pain In Extremity	3/114 (2.6%)		2/116 (1.7%)
Musculoskeletal Pain	1/114 (0.9%)		3/116 (2.6%)
Nervous system disorders
Headache	7/114 (6.1%)		5/116 (4.3%)
Dizziness	4/114 (3.5%)		0/116 (0%)
Migraine	0/114 (0%)		3/116 (2.6%)
Psychiatric disorders
Insomnia	13/114 (11.4%)		4/116 (3.4%)
Agitation	2/114 (1.8%)		6/116 (5.2%)
Anxiety	5/114 (4.4%)		3/116 (2.6%)
Renal and urinary disorders
Renal Failure Acute	0/114 (0%)		4/116 (3.4%)
Haematuria	3/114 (2.6%)		0/116 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/114 (3.5%)		2/116 (1.7%)
Epistaxis	5/114 (4.4%)		1/116 (0.9%)
Wheezing	5/114 (4.4%)		1/116 (0.9%)
Pleural Effusion	0/114 (0%)		5/116 (4.3%)
Pneumothorax	1/114 (0.9%)		4/116 (3.4%)
Haemoptysis	1/114 (0.9%)		3/116 (2.6%)
Respiratory Alkalosis	1/114 (0.9%)		3/116 (2.6%)
Stridor	0/114 (0%)		3/116 (2.6%)
Skin and subcutaneous tissue disorders
Rash	3/114 (2.6%)		5/116 (4.3%)
Erythema	1/114 (0.9%)		3/116 (2.6%)
Vascular disorders
Hypotension	7/114 (6.1%)		11/116 (9.5%)
Hypertension	5/114 (4.4%)		8/116 (6.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.