Evaluation of the Efficacy and Safety of Peramivir in Subjects With Uncomplicated Acute Influenza.

Measure Type	Primary
Measure Title	Time to Alleviation of Symptoms (Kaplan-Meier Estimate)
Measure Description	Descriptive statistics for the primary efficacy variables were tabulated by treatment group. Alleviation of symptoms was determined by data recorded in the Subject Diary. Treatment differences were assessed using a Cox Regression model with effects for current smoking behavior, treatment, and geographic region. Subjects who did not experience alleviation of symptoms were censored at the date of their last assessment. A Bonferroni adjustment for the primary comparisons of each active dose with placebo was performed.
Time Frame	Up to 14 days

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The intent-to-treat infected (ITTI) population included all randomized subjects who received study drug and had proven influenza by culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Of the 318 subjects in the ITTI population, one subject had insufficient data to determine Time to Alleviation of Symptoms.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	108	104	105
Time to Alleviation of Symptoms (Kaplan-Meier Estimate)  [Units: Hours] Median (95% Confidence Interval)	136.2   (114.3 to 165.8)	114.1   (95.2 to 145.5)	117.4   (78.0 to 135.9)

Statistical Analysis 1 for Time to Alleviation of Symptoms (Kaplan-Meier Estimate)

Measure Type	Secondary
Measure Title	Time to Resolution of Fever
Measure Description	The time to resolution of fever (defined as the number of hours from initiation of study drug until temperature is less than 37.2 degrees C [99.0 degrees F] and no antipyretic medications had been taken in the previous 12 hours) was estimated using the method of Kaplan-Meier. Differences between the treatment groups were assessed using the log rank statistic controlling for current smoking behavior. Subjects who did not have resolution of fever were censored at the time of the last assessment. No adjustment for multiple comparisons was performed.
Time Frame	Up to 14 days

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITTI population included all subjects who were randomized, received study drug, and had proven influenza by any one of the following: culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Subjects were analyzed according to the treatment to which they were randomized.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	108	104	104
Time to Resolution of Fever  [Units: Hours] Median (95% Confidence Interval)	58.1   (43.0 to 67.7)	43.6   (40.9 to 49.1)	42.9   (40.2 to 46.1)

Statistical Analysis 1 for Time to Resolution of Fever

Measure Type	Secondary
Measure Title	Time to Resumption of Ability to Perform Usual Activities
Measure Description	The time to resumption of a subject’s self-assessed ability to perform his or her usual activities was estimated using the method of Kaplan-Meier. Differences between the treatment groups were assessed using the log rank statistic controlling for current smoking behavior. Subjects who were not able to resume performance of usual activities were censored at the time of the last assessment.
Time Frame	Up to 14 days

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITTI population included all subjects who were randomized, received study drug, and had proven influenza by any one of the following: culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Subjects were analyzed according to the treatment to which they were randomized.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	108	104	103
Time to Resumption of Ability to Perform Usual Activities  [Units: Days] Median (95% Confidence Interval)	10.1   (9.1 to 11.4)	9.2   (8.1 to 11.4)	8.3   (7.3 to 10.4)

Statistical Analysis 1 for Time to Resumption of Ability to Perform Usual Activities

Measure Type	Secondary
Measure Title	Change From Baseline to Day 2 in Influenza Virus Titer
Measure Description	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).
Time Frame	Baseline and approximately 24 hours after treatment

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITTI population included all subjects who were randomized, received study drug, and had proven influenza by any one of the following: culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Subjects were analyzed according to the treatment to which they were randomized.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	103	97	100
Change From Baseline to Day 2 in Influenza Virus Titer  [Units: log10(TCID50/mL)] Median (Full Range)	-1.50   (-5.25 to 2.50)	-2.00   (-5.25 to 2.25)	-2.25   (-5.25 to 1.25)

Statistical Analysis 1 for Change From Baseline to Day 2 in Influenza Virus Titer

Measure Type	Secondary
Measure Title	Change From Baseline to Day 3 in Influenza Virus Titer
Measure Description	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).
Time Frame	Baseline and approximately 48 hours after treatment

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITTI population included all subjects who were randomized, received study drug, and had proven influenza by any one of the following: culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Subjects were analyzed according to the treatment to which they were randomized.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	104	98	98
Change From Baseline to Day 3 in Influenza Virus Titer  [Units: log10(TCID50/mL)] Median (Full Range)	-2.75   (-5.00 to 1.00)	-3.00   (-5.25 to 1.00)	-3.25   (-6.00 to 1.25)

Statistical Analysis 1 for Change From Baseline to Day 3 in Influenza Virus Titer

Measure Type	Secondary
Measure Title	Change From Baseline to Day 5 in Influenza Virus Titer
Measure Description	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).
Time Frame	Baseline and approximately 96 hours after treatment

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITTI population included all subjects who were randomized, received study drug, and had proven influenza by any one of the following: culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Subjects were analyzed according to the treatment to which they were randomized.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	103	98	100
Change From Baseline to Day 5 in Influenza Virus Titer  [Units: log10(TCID50/mL)] Median (Full Range)	-3.75   (-5.50 to -0.25)	-3.38   (-6.50 to 0.00)	-3.63   (-6.50 to 0.50)

Statistical Analysis 1 for Change From Baseline to Day 5 in Influenza Virus Titer

Measure Type	Secondary
Measure Title	Change From Baseline to Day 9 in Influenza Virus Titer
Measure Description	The change in viral titers was defined as the time-weighted change from baseline in log_10 tissue culture infective dose_50 (TCID_50/mL) and was summarized for each treatment group. The differences between the treatment groups were evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID_50/mL were obtained on Day 2 (approximately 24 hours after treatment), on Day 3 (approximately 48 hours after treatment), on Day 5 (approximately 96 hours after treatment), and on Day 9 (approximately 192 hours after treatment).
Time Frame	Baseline and approximately 192 hours after treatment

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ITTI population included all subjects who were randomized, received study drug, and had proven influenza by any one of the following: culture, PCR, or paired serology showing ≥ 4-fold increase in antibody to influenza A or B. Subjects were analyzed according to the treatment to which they were randomized.

Reporting Groups

	Description
Placebo	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (one injection of peramivir 150 mg and one injection of placebo).
Peramivir 300 mg	Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).

Measured Values

	Placebo	Peramivir 150 mg	Peramivir 300 mg
Participants Analyzed  [Units: Participants]	103	97	100
Change From Baseline to Day 9 in Influenza Virus Titer  [Units: log10(TCID50/mL)] Median (Full Range)	-3.75   (-5.75 to -0.25)	-3.75   (-6.50 to 2.00)	-3.75   (-6.75 to -0.50)

Statistical Analysis 1 for Change From Baseline to Day 9 in Influenza Virus Titer