Trial Outcomes & Findings for Evaluation of the Efficacy and Safety of Peramivir in Subjects With Uncomplicated Acute Influenza. (NCT NCT00419263)

NCT ID: NCT00419263

Last Updated: 2015-02-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

344 participants

Primary outcome timeframe

Up to 14 days

Results posted on

2015-02-12

Participant Flow

Participant milestones

Participant milestones
Measure
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).
Overall Study
STARTED
115
114
115
Overall Study
COMPLETED
112
112
112
Overall Study
NOT COMPLETED
3
2
3

Reasons for withdrawal

Reasons for withdrawal
Measure
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).
Overall Study
Lost to Follow-up
2
1
1
Overall Study
Randomized in Error, Not Treated
1
1
0
Overall Study
Adverse Event
0
0
1
Overall Study
Withdrawal by Subject
0
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=114 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=113 Participants
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
n=115 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Total
n=342 Participants
Total of all reporting groups
Age, Continuous
33.9 years
STANDARD_DEVIATION 12.05 • n=99 Participants
36.2 years
STANDARD_DEVIATION 15.59 • n=107 Participants
36.2 years
STANDARD_DEVIATION 13.25 • n=206 Participants
35.4 years
STANDARD_DEVIATION 13.71 • n=7 Participants
Age, Customized
18 - 27 years old
41 participants
n=99 Participants
37 participants
n=107 Participants
34 participants
n=206 Participants
112 participants
n=7 Participants
Age, Customized
28 - 37 years old
37 participants
n=99 Participants
31 participants
n=107 Participants
35 participants
n=206 Participants
103 participants
n=7 Participants
Age, Customized
38 - 47 years old
19 participants
n=99 Participants
21 participants
n=107 Participants
25 participants
n=206 Participants
65 participants
n=7 Participants
Age, Customized
48 - 57 years old
9 participants
n=99 Participants
10 participants
n=107 Participants
12 participants
n=206 Participants
31 participants
n=7 Participants
Age, Customized
≥ 58 years old
8 participants
n=99 Participants
13 participants
n=107 Participants
9 participants
n=206 Participants
30 participants
n=7 Participants
Age, Customized
Missing
0 participants
n=99 Participants
1 participants
n=107 Participants
0 participants
n=206 Participants
1 participants
n=7 Participants
Sex: Female, Male
Female
54 Participants
n=99 Participants
67 Participants
n=107 Participants
62 Participants
n=206 Participants
183 Participants
n=7 Participants
Sex: Female, Male
Male
60 Participants
n=99 Participants
46 Participants
n=107 Participants
53 Participants
n=206 Participants
159 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants
n=99 Participants
9 Participants
n=107 Participants
4 Participants
n=206 Participants
19 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
108 Participants
n=99 Participants
104 Participants
n=107 Participants
111 Participants
n=206 Participants
323 Participants
n=7 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Asian
7 Participants
n=99 Participants
4 Participants
n=107 Participants
7 Participants
n=206 Participants
18 Participants
n=7 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
6 Participants
n=99 Participants
8 Participants
n=107 Participants
4 Participants
n=206 Participants
18 Participants
n=7 Participants
Race (NIH/OMB)
Black or African American
21 Participants
n=99 Participants
18 Participants
n=107 Participants
17 Participants
n=206 Participants
56 Participants
n=7 Participants
Race (NIH/OMB)
White
77 Participants
n=99 Participants
78 Participants
n=107 Participants
81 Participants
n=206 Participants
236 Participants
n=7 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants
n=99 Participants
5 Participants
n=107 Participants
6 Participants
n=206 Participants
14 Participants
n=7 Participants
Body Mass Index at Screening
26.5 kg/m^2
STANDARD_DEVIATION 5.69 • n=99 Participants
27.5 kg/m^2
STANDARD_DEVIATION 6.23 • n=107 Participants
27.8 kg/m^2
STANDARD_DEVIATION 6.35 • n=206 Participants
27.2 kg/m^2
STANDARD_DEVIATION 6.11 • n=7 Participants
Current Smoking Behavior at Randomization
Smoker
26 participants
n=99 Participants
22 participants
n=107 Participants
25 participants
n=206 Participants
73 participants
n=7 Participants
Current Smoking Behavior at Randomization
Nonsmoker
88 participants
n=99 Participants
91 participants
n=107 Participants
90 participants
n=206 Participants
269 participants
n=7 Participants
Estimated Time of Onset of Symptoms at Screening
0 - 12 hours ago
1 participants
n=99 Participants
4 participants
n=107 Participants
4 participants
n=206 Participants
9 participants
n=7 Participants
Estimated Time of Onset of Symptoms at Screening
> 12 - 24 hours ago
37 participants
n=99 Participants
32 participants
n=107 Participants
25 participants
n=206 Participants
94 participants
n=7 Participants
Estimated Time of Onset of Symptoms at Screening
> 24 - 36 hours ago
45 participants
n=99 Participants
43 participants
n=107 Participants
46 participants
n=206 Participants
134 participants
n=7 Participants
Estimated Time of Onset of Symptoms at Screening
> 36 - 48 hours ago
31 participants
n=99 Participants
34 participants
n=107 Participants
40 participants
n=206 Participants
105 participants
n=7 Participants
Initial Composite Symptom Score
14.3 units on a scale
STANDARD_DEVIATION 3.70 • n=99 Participants
14.3 units on a scale
STANDARD_DEVIATION 3.22 • n=107 Participants
14.1 units on a scale
STANDARD_DEVIATION 3.92 • n=206 Participants
14.2 units on a scale
STANDARD_DEVIATION 3.62 • n=7 Participants
Influenza Infection
Negative
5 participants
n=99 Participants
9 participants
n=107 Participants
9 participants
n=206 Participants
23 participants
n=7 Participants
Influenza Infection
Positive
109 participants
n=99 Participants
104 participants
n=107 Participants
105 participants
n=206 Participants
318 participants
n=7 Participants
Influenza Infection
Missing
0 participants
n=99 Participants
0 participants
n=107 Participants
1 participants
n=206 Participants
1 participants
n=7 Participants
Body Surface Area
1.9 m^2
STANDARD_DEVIATION 0.26 • n=99 Participants
1.9 m^2
STANDARD_DEVIATION 0.25 • n=107 Participants
1.9 m^2
STANDARD_DEVIATION 0.28 • n=206 Participants
1.9 m^2
STANDARD_DEVIATION 0.26 • n=7 Participants

PRIMARY outcome

Timeframe: Up to 14 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=108 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=104 Participants
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
n=105 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Time to Alleviation of Symptoms (Kaplan-Meier Estimate)
136.2 Hours
Interval 114.3 to 165.8
114.1 Hours
Interval 95.2 to 145.5
117.4 Hours
Interval 78.0 to 135.9

SECONDARY outcome

Timeframe: Up to 14 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=108 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=104 Participants
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
n=104 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Time to Resolution of Fever
58.1 Hours
Interval 43.0 to 67.7
43.6 Hours
Interval 40.9 to 49.1
42.9 Hours
Interval 40.2 to 46.1

SECONDARY outcome

Timeframe: Up to 14 days

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=108 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=104 Participants
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
n=103 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Time to Resumption of Ability to Perform Usual Activities
10.1 Days
Interval 9.1 to 11.4
9.2 Days
Interval 8.1 to 11.4
8.3 Days
Interval 7.3 to 10.4

SECONDARY outcome

Timeframe: Baseline and approximately 24 hours after treatment

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=103 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=97 Participants
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
n=100 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Change From Baseline to Day 2 in Influenza Virus Titer
-1.50 log10(TCID50/mL)
Interval -5.25 to 2.5
-2.00 log10(TCID50/mL)
Interval -5.25 to 2.25
-2.25 log10(TCID50/mL)
Interval -5.25 to 1.25

SECONDARY outcome

Timeframe: Baseline and approximately 48 hours after treatment

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=104 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=98 Participants
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
n=98 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Change From Baseline to Day 3 in Influenza Virus Titer
-2.75 log10(TCID50/mL)
Interval -5.0 to 1.0
-3.00 log10(TCID50/mL)
Interval -5.25 to 1.0
-3.25 log10(TCID50/mL)
Interval -6.0 to 1.25

SECONDARY outcome

Timeframe: Baseline and approximately 96 hours after treatment

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=103 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=98 Participants
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
n=100 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Change From Baseline to Day 5 in Influenza Virus Titer
-3.75 log10(TCID50/mL)
Interval -5.5 to -0.25
-3.38 log10(TCID50/mL)
Interval -6.5 to 0.0
-3.63 log10(TCID50/mL)
Interval -6.5 to 0.5

SECONDARY outcome

Timeframe: Baseline and approximately 192 hours after treatment

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=103 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=97 Participants
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
n=100 Participants
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Change From Baseline to Day 9 in Influenza Virus Titer
-3.75 log10(TCID50/mL)
Interval -5.75 to -0.25
-3.75 log10(TCID50/mL)
Interval -6.5 to 2.0
-3.75 log10(TCID50/mL)
Interval -6.75 to -0.5

Adverse Events

Placebo

Serious events: 1 serious events
Other events: 31 other events
Deaths: 0 deaths

Peramivir 150 mg

Serious events: 0 serious events
Other events: 27 other events
Deaths: 0 deaths

Peramivir 300 mg

Serious events: 1 serious events
Other events: 25 other events
Deaths: 0 deaths

Total

Serious events: 2 serious events
Other events: 83 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=114 participants at risk
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=113 participants at risk
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
n=115 participants at risk
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Total
n=342 participants at risk
Total number of subjects who received at least 1 dose of study drug
Infections and infestations
Meningitis
0.00%
0/114
0.00%
0/113
0.87%
1/115 • Number of events 1
0.29%
1/342 • Number of events 1
Infections and infestations
Pyelonephritis
0.88%
1/114 • Number of events 1
0.00%
0/113
0.00%
0/115
0.29%
1/342 • Number of events 1

Other adverse events

Other adverse events
Measure
Placebo
n=114 participants at risk
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of placebo).
Peramivir 150 mg
n=113 participants at risk
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
n=115 participants at risk
Single dose administered as bilateral 2-mL intramuscular injections in each gluteal muscle (2 injections of peramivir 150 mg).
Total
n=342 participants at risk
Total number of subjects who received at least 1 dose of study drug
Gastrointestinal disorders
Diarrhoea
4.4%
5/114
4.4%
5/113
5.2%
6/115
4.7%
16/342
Gastrointestinal disorders
Nausea
6.1%
7/114
6.2%
7/113
7.8%
9/115
6.7%
23/342
Gastrointestinal disorders
Vomiting
4.4%
5/114
3.5%
4/113
1.7%
2/115
3.2%
11/342
Nervous system disorders
Dizziness
2.6%
3/114
2.7%
3/113
4.3%
5/115
3.2%
11/342
Nervous system disorders
Syncope vasovagal
3.5%
4/114
1.8%
2/113
0.00%
0/115
1.8%
6/342
Renal and urinary disorders
Proteinuria
6.1%
7/114
8.8%
10/113
4.3%
5/115
6.4%
22/342
Investigations
Aspartate aminotransferase increased
1.8%
2/114
1.8%
2/113
2.6%
3/115
2.0%
7/342
Respiratory, thoracic and mediastinal disorders
Asthma
3.5%
4/114
0.88%
1/113
0.87%
1/115
1.8%
6/342
Respiratory, thoracic and mediastinal disorders
Epistaxis
0.00%
0/114
0.88%
1/113
2.6%
3/115
1.2%
4/342
Psychiatric disorders
Insomnia
1.8%
2/114
4.4%
5/113
0.00%
0/115
2.0%
7/342

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