Trial Outcomes & Findings for Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza (NCT NCT00453999)

Last Updated: 2015-02-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

137 participants

Primary outcome timeframe

14 days

Results posted on

2015-02-12

Participant Flow

Participant milestones

Participant milestones
Measure	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)
Overall Study STARTED	45	46	46
Overall Study COMPLETED	40	41	43
Overall Study NOT COMPLETED	5	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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)
Overall Study Adverse Event	1	2	1
Overall Study Lost to Follow-up	0	1	1
Overall Study Withdrawal by Subject	2	1	1
Overall Study Subject Request	2	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peramivir 200 mg n=45 Participants 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 n=46 Participants Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=46 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)	Total n=137 Participants Total of all reporting groups
Age, Continuous	56.9 years STANDARD_DEVIATION 24.0 • n=5 Participants	58.5 years STANDARD_DEVIATION 20.9 • n=7 Participants	62.0 years STANDARD_DEVIATION 21.3 • n=5 Participants	59.2 years STANDARD_DEVIATION 22.0 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	26 Participants n=7 Participants	25 Participants n=5 Participants	76 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	20 Participants n=7 Participants	21 Participants n=5 Participants	61 Participants n=4 Participants
Race/Ethnicity, Customized White or Caucasian	23 participants n=5 Participants	21 participants n=7 Participants	20 participants n=5 Participants	64 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=5 Participants	14 participants n=7 Participants	12 participants n=5 Participants	34 participants n=4 Participants
Race/Ethnicity, Customized Asian	13 participants n=5 Participants	10 participants n=7 Participants	13 participants n=5 Participants	36 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Height	163.0 cm STANDARD_DEVIATION 9.9 • n=5 Participants	161.6 cm STANDARD_DEVIATION 11.8 • n=7 Participants	168.4 cm STANDARD_DEVIATION 11.8 • n=5 Participants	164.4 cm STANDARD_DEVIATION 11.5 • n=4 Participants
Weight	64.9 kg STANDARD_DEVIATION 19.8 • n=5 Participants	72.4 kg STANDARD_DEVIATION 22.9 • n=7 Participants	79.5 kg STANDARD_DEVIATION 22.7 • n=5 Participants	72.4 kg STANDARD_DEVIATION 22.5 • n=4 Participants
Duration of Illness at Randomization < 48 hours	31 participants n=5 Participants	32 participants n=7 Participants	31 participants n=5 Participants	94 participants n=4 Participants
Duration of Illness at Randomization >= 48 hours to <=72 hours	14 participants n=5 Participants	14 participants n=7 Participants	15 participants n=5 Participants	43 participants n=4 Participants
Initial Composite Symptom Score	12.7 units on a scale STANDARD_DEVIATION 5.19 • n=5 Participants	12.2 units on a scale STANDARD_DEVIATION 5.95 • n=7 Participants	12.3 units on a scale STANDARD_DEVIATION 5.46 • n=5 Participants	12.4 units on a scale STANDARD_DEVIATION 5.51 • n=4 Participants
Current Smoking Status Smoker	8 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	17 participants n=4 Participants
Current Smoking Status Nonsmoker	36 participants n=5 Participants	40 participants n=7 Participants	42 participants n=5 Participants	118 participants n=4 Participants
Current Smoking Status Missing	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Influenza Infection Confirmed Influenza A	26 participants n=5 Participants	34 participants n=7 Participants	30 participants n=5 Participants	90 participants n=4 Participants
Influenza Infection Confirmed Influenza B	15 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants	32 participants n=4 Participants
Influenza Infection Not confirmed	4 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	15 participants n=4 Participants
Transcutaneous Oxygen Saturation at Randomization < 94%	14 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	42 participants n=4 Participants
Transcutaneous Oxygen Saturation at Randomization >= 94%	31 participants n=5 Participants	32 participants n=7 Participants	32 participants n=5 Participants	95 participants n=4 Participants

PRIMARY outcome

Timeframe: 14 days

Population: The intent-to-treat infected (ITTI) population included all subjects who were randomized, received at least 1 dose of study drug, and had confirmed influenza infection by viral culture, PCR, and/or paired acute and convalescent serology specimens that demonstrated at least a 4-fold increase in antibody titer against influenza A or B.

Outcome measures

Outcome measures
Measure	Peramivir 200 mg n=41 Participants 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 n=40 Participants Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=41 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Time to Clinical Stability (Kaplan-Meier Estimate)	23.7 hours Interval 16.0 to 38.9	37.0 hours Interval 22.0 to 48.7	28.1 hours Interval 22.0 to 37.0

SECONDARY outcome

Timeframe: Baseline, Days 2, 3, 4, 5, 10, and 14

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.

Outcome measures

SECONDARY outcome

Timeframe: 14 days

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).

Outcome measures

Outcome measures
Measure	Peramivir 200 mg n=40 Participants 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 n=39 Participants Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=41 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate)	8.8 hours Interval 4.0 to 14.5	9.0 hours Interval 6.8 to The number of observed events was too small to allow estimation of the required parameter.	13.7 hours Interval 10.0 to 20.7

SECONDARY outcome

Timeframe: 14 days

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.

Outcome measures

Outcome measures
Measure	Peramivir 200 mg n=41 Participants 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 n=40 Participants Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=41 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 14 days

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.

Outcome measures

Outcome measures
Measure	Peramivir 200 mg n=41 Participants 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 n=40 Participants Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=41 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Time to Hospital Discharge (Kaplan-Meier Estimate)	4.0 hours Interval 3.0 to 4.7	3.8 hours Interval 2.7 to 4.8	4.0 hours Interval 2.9 to 4.6

SECONDARY outcome

Timeframe: Baseline, and 12, 24, 36, 48, 72, and 96 hours

Population: Among the 122 subjects with confirmed influenza (intent-to-treat infected \[ITTI\]) population, a total of 112 subjects had positive virus cultures obtained from baseline nasopharyngeal specimens.

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.

Outcome measures

Outcome measures
Measure	Peramivir 200 mg n=39 Participants 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 n=34 Participants Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=39 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration <48 Hours: Baseline	3.6 log10 TCID50/mL Standard Deviation 1.33	3.5 log10 TCID50/mL Standard Deviation 1.01	3.4 log10 TCID50/mL Standard Deviation 1.44
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration <48 Hours: Change at 12 hours	-1.5 log10 TCID50/mL Standard Deviation 1.33	-1.6 log10 TCID50/mL Standard Deviation 1.29	-1.5 log10 TCID50/mL Standard Deviation 1.01
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration <48 Hours: Change at 24 hours	-2.5 log10 TCID50/mL Standard Deviation 0.93	-2.2 log10 TCID50/mL Standard Deviation 0.84	-2.2 log10 TCID50/mL Standard Deviation 0.99
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration <48 Hours: Change at 48 hours	-2.4 log10 TCID50/mL Standard Deviation 0.93	-2.9 log10 TCID50/mL Standard Deviation 0.77	-2.5 log10 TCID50/mL Standard Deviation 1.45
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration <48 Hours: Change at 96 hours	-2.8 log10 TCID50/mL Standard Deviation 1.28	-3.0 log10 TCID50/mL Standard Deviation 0.97	-2.8 log10 TCID50/mL Standard Deviation 1.05
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration ≥48 and ≤72 hours: Baseline	2.8 log10 TCID50/mL Standard Deviation 1.38	2.6 log10 TCID50/mL Standard Deviation 1.35	2.5 log10 TCID50/mL Standard Deviation 1.27
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration ≥48 and ≤72 hours: Change at 12 hours	-1.1 log10 TCID50/mL Standard Deviation 1.03	-1.5 log10 TCID50/mL Standard Deviation 1.27	-0.7 log10 TCID50/mL Standard Deviation 1.12
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration ≥48 and ≤72 hours: Change at 24 hours	-1.4 log10 TCID50/mL Standard Deviation 0.92	-1.7 log10 TCID50/mL Standard Deviation 1.22	-1.0 log10 TCID50/mL Standard Deviation 0.75
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration ≥48 and ≤72 hours: Change at 48 hours	-1.8 log10 TCID50/mL Standard Deviation 1.17	-1.9 log10 TCID50/mL Standard Deviation 1.16	-1.5 log10 TCID50/mL Standard Deviation 0.85
Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) Duration ≥48 and ≤72 hours: Change at 96 hours	-2.6 log10 TCID50/mL Standard Deviation 1.29	-2.0 log10 TCID50/mL Standard Deviation 1.38	-1.7 log10 TCID50/mL Standard Deviation 1.44

Adverse Events

Peramivir 200 mg

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Peramivir 400 mg

Serious events: 8 serious events

Other events: 21 other events

Deaths: 0 deaths

Oseltamivir

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

William P. Sheridan, MBBS

BioCryst Pharmaceuticals, Inc.

Phone: 919-859-1302

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Peramivir 200 mg n=41 Participants 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 n=40 Participants Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=41 Participants Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Change at Day 10	-1.2 units on a scale Standard Deviation 1.03	-1.1 units on a scale Standard Deviation 1.15	-1.2 units on a scale Standard Deviation 1.18
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Change at Day 2	-0.2 units on a scale Standard Deviation 0.95	-0.3 units on a scale Standard Deviation 1.09	-0.3 units on a scale Standard Deviation 0.80
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Change at Day 3	-0.8 units on a scale Standard Deviation 1.05	-0.7 units on a scale Standard Deviation 1.24	-0.8 units on a scale Standard Deviation 1.04
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Change at Day 4	-0.9 units on a scale Standard Deviation 1.13	-0.9 units on a scale Standard Deviation 1.24	-1.1 units on a scale Standard Deviation 1.18
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Change at Day 5	-1.1 units on a scale Standard Deviation 1.07	-0.9 units on a scale Standard Deviation 1.20	-1.1 units on a scale Standard Deviation 1.24
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Baseline	1.3 units on a scale Standard Deviation 1.09	1.1 units on a scale Standard Deviation 1.17	1.2 units on a scale Standard Deviation 1.19
Change From Baseline in Scores of Symptoms of Influenza Sore Throat: Change at Day 14	-1.2 units on a scale Standard Deviation 1.05	-1.1 units on a scale Standard Deviation 1.16	-1.1 units on a scale Standard Deviation 1.17
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Baseline	1.3 units on a scale Standard Deviation 1.17	1.5 units on a scale Standard Deviation 1.03	1.3 units on a scale Standard Deviation 1.08
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Change at Day 2	-0.2 units on a scale Standard Deviation 1.06	-0.5 units on a scale Standard Deviation 0.82	-0.3 units on a scale Standard Deviation 0.82
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Change at Day 3	-0.7 units on a scale Standard Deviation 1.18	-0.9 units on a scale Standard Deviation 0.99	-0.8 units on a scale Standard Deviation 0.96
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Change at Day 4	-0.8 units on a scale Standard Deviation 1.32	-1.1 units on a scale Standard Deviation 1.06	-1.0 units on a scale Standard Deviation 1.16
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Change at Day 5	-0.9 units on a scale Standard Deviation 1.27	-1.2 units on a scale Standard Deviation 1.17	-1.1 units on a scale Standard Deviation 1.10
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Change at Day 10	-1.1 units on a scale Standard Deviation 1.23	-1.2 units on a scale Standard Deviation 1.27	-1.1 units on a scale Standard Deviation 1.17
Change From Baseline in Scores of Symptoms of Influenza Nasal Congestion: Change at Day 14	-1.0 units on a scale Standard Deviation 1.22	-1.2 units on a scale Standard Deviation 1.17	-1.3 units on a scale Standard Deviation 1.08
Change From Baseline in Scores of Symptoms of Influenza Cough: Baseline	2.2 units on a scale Standard Deviation 0.73	2.0 units on a scale Standard Deviation 0.77	2.1 units on a scale Standard Deviation 0.76
Change From Baseline in Scores of Symptoms of Influenza Cough: Change at Day 2	-0.4 units on a scale Standard Deviation 0.88	-0.3 units on a scale Standard Deviation 0.74	-0.2 units on a scale Standard Deviation 0.81
Change From Baseline in Scores of Symptoms of Influenza Cough: Change at Day 3	-0.9 units on a scale Standard Deviation 0.91	-0.9 units on a scale Standard Deviation 1.07	-0.9 units on a scale Standard Deviation 0.87
Change From Baseline in Scores of Symptoms of Influenza Cough: Change at Day 4	-1.1 units on a scale Standard Deviation 1.10	-1.1 units on a scale Standard Deviation 1.05	-1.0 units on a scale Standard Deviation 1.07
Change From Baseline in Scores of Symptoms of Influenza Cough: Change at Day 5	-1.2 units on a scale Standard Deviation 0.97	-1.1 units on a scale Standard Deviation 1.23	-1.1 units on a scale Standard Deviation 1.17
Change From Baseline in Scores of Symptoms of Influenza Cough: Change at Day 10	-1.4 units on a scale Standard Deviation 0.97	-1.2 units on a scale Standard Deviation 1.07	-1.3 units on a scale Standard Deviation 1.11
Change From Baseline in Scores of Symptoms of Influenza Cough: Change at Day 14	-1.6 units on a scale Standard Deviation 1.06	-1.4 units on a scale Standard Deviation 1.01	-1.5 units on a scale Standard Deviation 1.09
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Baseline	1.8 units on a scale Standard Deviation 1.30	1.9 units on a scale Standard Deviation 1.13	1.9 units on a scale Standard Deviation 1.09
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Change at Day 2	-0.8 units on a scale Standard Deviation 1.01	-0.8 units on a scale Standard Deviation 0.91	-0.8 units on a scale Standard Deviation 1.08
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Change at Day 3	-1.3 units on a scale Standard Deviation 1.14	-1.4 units on a scale Standard Deviation 1.18	-1.4 units on a scale Standard Deviation 1.14
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Change at Day 4	-1.5 units on a scale Standard Deviation 1.28	-1.6 units on a scale Standard Deviation 1.21	-1.6 units on a scale Standard Deviation 1.21
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Change at Day 5	-1.6 units on a scale Standard Deviation 1.31	-1.6 units on a scale Standard Deviation 1.23	-1.7 units on a scale Standard Deviation 1.31
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Change at Day 10	-1.7 units on a scale Standard Deviation 1.38	-1.7 units on a scale Standard Deviation 1.12	-1.9 units on a scale Standard Deviation 1.09
Change From Baseline in Scores of Symptoms of Influenza Aches and Pains: Change at Day 14	-1.7 units on a scale Standard Deviation 1.35	-1.6 units on a scale Standard Deviation 1.11	-1.7 units on a scale Standard Deviation 1.30
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Baseline	2.3 units on a scale Standard Deviation 0.78	2.0 units on a scale Standard Deviation 0.96	2.3 units on a scale Standard Deviation 0.82
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Change at Day 2	-0.9 units on a scale Standard Deviation 0.96	-0.5 units on a scale Standard Deviation 1.12	-1.0 units on a scale Standard Deviation 1.11
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Change at Day 3	-1.2 units on a scale Standard Deviation 1.02	-1.0 units on a scale Standard Deviation 1.26	-1.1 units on a scale Standard Deviation 1.17
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Change at Day 4	-1.4 units on a scale Standard Deviation 1.21	-1.2 units on a scale Standard Deviation 1.30	-1.6 units on a scale Standard Deviation 1.11
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Change at Day 5	-1.6 units on a scale Standard Deviation 1.09	-1.3 units on a scale Standard Deviation 1.27	-1.7 units on a scale Standard Deviation 1.09
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Change at Day 10	-1.7 units on a scale Standard Deviation 1.05	-1.4 units on a scale Standard Deviation 1.13	-1.7 units on a scale Standard Deviation 1.09
Change From Baseline in Scores of Symptoms of Influenza Fatigue: Change at Day 14	-1.7 units on a scale Standard Deviation 1.13	-1.6 units on a scale Standard Deviation 1.01	-2.0 units on a scale Standard Deviation 0.97
Change From Baseline in Scores of Symptoms of Influenza Headache: Baseline	1.5 units on a scale Standard Deviation 1.22	1.3 units on a scale Standard Deviation 1.34	1.4 units on a scale Standard Deviation 1.30
Change From Baseline in Scores of Symptoms of Influenza Headache: Change at Day 2	-0.5 units on a scale Standard Deviation 1.11	-0.5 units on a scale Standard Deviation 1.12	-0.6 units on a scale Standard Deviation 0.94
Change From Baseline in Scores of Symptoms of Influenza Headache: Change at Day 3	-0.9 units on a scale Standard Deviation 1.16	-1.0 units on a scale Standard Deviation 1.26	-1.0 units on a scale Standard Deviation 1.10
Change From Baseline in Scores of Symptoms of Influenza Headache: Change at Day 4	-1.0 units on a scale Standard Deviation 1.25	-1.1 units on a scale Standard Deviation 1.30	-1.1 units on a scale Standard Deviation 1.30
Change From Baseline in Scores of Symptoms of Influenza Headache: Change at Day 5	-1.2 units on a scale Standard Deviation 1.21	-1.1 units on a scale Standard Deviation 1.28	-1.3 units on a scale Standard Deviation 1.30
Change From Baseline in Scores of Symptoms of Influenza Headache: Change at Day 10	-1.3 units on a scale Standard Deviation 1.24	-1.2 units on a scale Standard Deviation 1.35	-1.4 units on a scale Standard Deviation 1.26
Change From Baseline in Scores of Symptoms of Influenza Headache: Change at Day 14	-1.3 units on a scale Standard Deviation 1.19	-1.2 units on a scale Standard Deviation 1.35	-1.3 units on a scale Standard Deviation 1.34
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Baseline	2.1 units on a scale Standard Deviation 1.04	1.9 units on a scale Standard Deviation 0.99	1.8 units on a scale Standard Deviation 1.20
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Change at Day 2	-1.4 units on a scale Standard Deviation 1.02	-1.0 units on a scale Standard Deviation 0.94	-1.0 units on a scale Standard Deviation 1.15
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Change at Day 3	-1.5 units on a scale Standard Deviation 1.01	-1.5 units on a scale Standard Deviation 0.93	-1.6 units on a scale Standard Deviation 1.20
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Change at Day 4	-1.8 units on a scale Standard Deviation 1.15	-1.8 units on a scale Standard Deviation 0.97	-1.6 units on a scale Standard Deviation 1.48
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Change at Day 5	-1.9 units on a scale Standard Deviation 1.02	-1.8 units on a scale Standard Deviation 1.02	-1.8 units on a scale Standard Deviation 1.20
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Change at Day 10	-2.0 units on a scale Standard Deviation 1.07	-1.8 units on a scale Standard Deviation 1.00	-1.8 units on a scale Standard Deviation 1.18
Change From Baseline in Scores of Symptoms of Influenza Feeling Feverish: Change at Day 14	-1.9 units on a scale Standard Deviation 1.21	-1.7 units on a scale Standard Deviation 1.01	-1.8 units on a scale Standard Deviation 1.23

Measure	Peramivir 200 mg n=45 participants at risk 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 n=46 participants at risk Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Oseltamivir n=46 participants at risk Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Nervous system disorders Presyncope	2.2% 1/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Infections and infestations Pneumonia	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	6.5% 3/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Infections and infestations Respiratory tract infection	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Infections and infestations Viral myocarditis	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Blood and lymphatic system disorders Anaemia	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Blood and lymphatic system disorders Hypocoagulable state	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Gastrointestinal disorders Diarrhoea	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Renal and urinary disorders Proteinuria	2.2% 1/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Renal and urinary disorders Urinary retention	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Cardiac disorders Supraventricular tachycardia	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/45 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	0.00% 0/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.	2.2% 1/46 • Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14. For subjects who experienced the same coded event more than once, only one event is presented.