A Phase II, Multicenter, Randomized, Placebo -Controlled, Study To Evaluate The Efficacy and Safety Of Intramuscular Peramivir 600 mg In Subjects With Uncomplicated Acute Influenza

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Placebo	Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.
Peramivir 600 mg	Peramivir 600 mg administered as bilateral 2-mL intramuscular injection.

Participant Flow:   Overall Study

	Placebo	Peramivir 600 mg
STARTED	203	202
COMPLETED	199	197
NOT COMPLETED	4	5
Lost to Follow-up	3	3
Did not receive study drug	1	2

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.
Intent-to-Treat (ITT)

Reporting Groups

	Description
Placebo	Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.
Peramivir 600 mg	Peramivir 600 mg administered as bilateral 2-mL intramuscular injection.
Total	Total of all reporting groups

Baseline Measures

	Placebo	Peramivir 600 mg	Total
Overall Participants Analyzed  [Units: Participants]	203	202	405
Age  [Units: Years] Mean (Standard Deviation)	35  (11.3)	35  (12.1)	35  (11.7)
Gender  [Units: Participants]
Female	104	102	206
Male	99	100	199
Race/Ethnicity, Customized [1]  [Units: Participants]
White or Caucasian	101	106	207
Black or African American	68	61	129
Asian	15	15	30
American Indian or Alaska Native	5	3	8
Other	14	17	31
[1] Participants may have been counted in more than 1 category; therefore, numbers may add up to more than the total number of participants.
Body Mass Index (BMI)  [Units: Kg/m^2] Mean (Standard Deviation)	27.5  (6.73)	27.2  (6.12)	27.4  (6.43)
Estimated Time of Onset of Symptoms at Screening  [Units: Participants]
0-12 h Ago	13	16	29
12-24 h Ago	91	81	172
24-36 h Ago	99	104	203
Data Missing	0	1	1
Initial Composite Symptom Score [1]  [Units: Units on a scale] Mean (Standard Deviation)	14  (4.3)	14  (3.9)	14  (4.1)
[1] Initial Composite Symptom Score is defined as the sum of the 7 symptoms of influenza initially recorded by the subject in the diary (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]); for the composite score, individual scores were summed, with a range from 0 to 21.
Rapid Antigen Test (RAT) Results [1]  [Units: Participants]
Positive	202	200	402
No data reported	1	2	3
[1] Positive influenza infection confirmed by PCR or virus culture.
Confirmed Influenza Infection Result  [Units: Participants]
Positive by PCR Only	27	38	65
Positive by Viral Culture Only	0	0	0
Positive by PCR and Viral Culture	147	122	269
Negative by PCR and Viral Culture	28	40	68
No Result/Sample	1	2	3
Current Smoking Behavior  [Units: Participants]
Smoker	37	37	74
Nonsmoker	166	165	331

1.  Primary:

Time to Alleviation of Symptoms (Kaplan-Meier Estimate)   [ Time Frame: Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 ]

2.  Secondary:

Change in Influenza Virus Shedding   [ Time Frame: Baseline and Days 3, 4, 9 ]

3.  Other Pre-specified:

Subject’s Severity of Illness (Score*Hours)   [ Time Frame: Information collected predose on Day 1 and then once daily through Day 14 ]

4.  Other Pre-specified:

Time to Resolution of Fever   [ Time Frame: Information collected twice daily beginning predose on Day 1 and through Day 9, then once daily through Day 14 ]

5.  Other Pre-specified:

Incidence of Influenza-related Complications   [ Time Frame: 14 days ]

6.  Other Pre-specified:

Baseline Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Mean IC50)   [ Time Frame: Baseline ]

7.  Other Pre-specified:

Change in Influenza Virus A (H1N1) Susceptibility to Neuraminidase Inhibitors (Fold Change From Baseline in IC50)   [ Time Frame: Baseline and up to 14 days ]

8.  Other Pre-specified:

Baseline Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50)   [ Time Frame: Baseline and up to 14 days ]

9.  Other Pre-specified:

Change in Influenza Virus B Susceptibility to Neuraminidase Inhibitors (Mean Baseline IC50 and Fold Change From Baseline in IC50)   [ Time Frame: Baseline and up to 14 days ]

Time Frame	Treatment-emergent AEs included any AEs that occurred after treatment on Day 1 and up to and including the visit on Day 14.
Additional Description	Three of 405 subjects were randomized but did not receive treatment and were therefore not included in the safety population (N = 402; 202 in the Placebo group and 200 in the Peramivir 600 mg group).

Frequency Threshold

Threshold above which other adverse events are reported	2%

Reporting Groups

	Description
Placebo	Placebo (buffered diluent) administered as bilateral 2-mL intramuscular injection.
Peramivir 600 mg	Peramivir 600 mg administered as bilateral 2-mL intramuscular injection.

Other Adverse Events

	Placebo	Peramivir 600 mg
Total, Other (not including serious) Adverse Events
# participants affected / at risk	27/202 (13.37%)	31/200 (15.50%)
Gastrointestinal disorders
Nausea † 1
# participants affected / at risk	10/202 (4.95%)	7/200 (3.50%)
Diarrhoea † 1
# participants affected / at risk	8/202 (3.96%)	6/200 (3.00%)
Vomiting † 1
# participants affected / at risk	0/202 (0.00%)	4/200 (2.00%)
General disorders
Injection site pain † 1
# participants affected / at risk	2/202 (0.99%)	4/200 (2.00%)
Infections and infestations
Urinary tract infection † 1
# participants affected / at risk	5/202 (2.48%)	1/200 (0.50%)
Investigations
Blood creatine phosphokinase increased † 1
# participants affected / at risk	1/202 (0.50%)	11/200 (5.50%)
Nervous system disorders
Headache † 1
# participants affected / at risk	5/202 (2.48%)	0/200 (0.00%)

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The majority of the subjects enrolled in this study with a laboratory confirmed influenza infection were infected with an influenza A/H1N1 virus containing an H275Y mutation associated with reduced susecptibility to peramivir and oseltamivir.