Trial Outcomes & Findings for Intramuscular Peramivir in Subjects With Uncomplicated Acute Influenza (NCT NCT00610935)

Last Updated: 2021-03-17

Results Overview

The primary efficacy endpoint was the time to alleviation of symptoms of influenza in subjects diagnosed with influenza, defined as the time from injection of study drug to the start of the time period when a subject had Alleviation of Symptoms. A subject had Alleviation of Symptoms if each of the seven symptoms of influenza (cough, sore throat, nasal obstruction, myalgia \[aches and pains\], headache, feverishness, and fatigue) as self-assessed and recorded in the subject diary were either absent or were present at no more than mild severity level and at this status for at least 21.5 hours (24 hours minus 10%). No statistical testing was performed.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

82 participants

Primary outcome timeframe

Up to 14 days

Results posted on

2021-03-17

Participant Flow

Subjects were centrally randomized in a ratio of 2:1 to a single dose of IM peramivir 300 mg or placebo, in accordance with a computer-generated randomization schedule prepared by a non-study statistician. Each subject's assignment to treatment was stratified according to smoking status and RAT test for influenza A or B.

Participant milestones

Participant milestones
Measure	Placebo Placebo intramuscular injection	Peramivir Single intramuscular injection of 300mg peramivir
Overall Study STARTED	25	57
Overall Study ITTI Population	25	55
Overall Study ITT Population	25	57
Overall Study COMPLETED	24	54
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo intramuscular injection	Peramivir Single intramuscular injection of 300mg peramivir
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	2
Overall Study Sponsor Discontinuation	1	0

Baseline Characteristics

Intramuscular Peramivir in Subjects With Uncomplicated Acute Influenza

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=25 Participants Placebo intramuscular injection	Peramivir n=57 Participants Single intramuscular injection of 300mg peramivir	Total n=82 Participants Total of all reporting groups
Age, Continuous	33.9 years STANDARD_DEVIATION 8.86 • n=5 Participants	32.6 years STANDARD_DEVIATION 12.67 • n=7 Participants	33.0 years STANDARD_DEVIATION 11.60 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	28 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	29 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	41 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Current Smoking Behavior at Randomization Smoker	4 participants n=5 Participants	14 participants n=7 Participants	18 participants n=5 Participants
Current Smoking Behavior at Randomization Non-smoker	21 participants n=5 Participants	43 participants n=7 Participants	64 participants n=5 Participants
Influenza PCR Results Negative	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Influenza PCR Results Influenza A (H1N1)	5 participants n=5 Participants	16 participants n=7 Participants	21 participants n=5 Participants
Influenza PCR Results Influenza A (H3N2)	15 participants n=5 Participants	33 participants n=7 Participants	48 participants n=5 Participants
Influenza PCR Results Influenza A (IND)	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Influenza PCR Results Influenza B	4 participants n=5 Participants	6 participants n=7 Participants	10 participants n=5 Participants
Influenza PCR Results Influenza A and B	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 14 days

Population: A total of 80 subjects met the criteria for inclusion in the ITTI population as defined by a positive PCR assay for influenza A or B from the nasopharyngeal specimen obtained prior to administration of study treatment. Seventy-nine of these were included in the primary efficacy analysis for whom data for time to symptom alleviation were available; There was insufficient data from one subject in the placebo group to enable determination of the Time to Alleviation of Symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants Placebo intramuscular injection	Peramivir n=55 Participants Single intramuscular injection of 300mg peramivir
The Time to Alleviation of Clinical Signs and Symptoms of Influenza	118.3 hours Interval 81.3 to 175.5	103.9 hours Interval 81.7 to 126.8

SECONDARY outcome

Timeframe: Change from baseline assessed on days 3, 5 and 9.

Population: The Intent To Treat Infected population (ITTI) population included all subjects who were randomized, received study drug, and had confirmed influenza A and/or B by primary viral culture or PCR.

The change in influenza viral titers was defined as the time-weighted change from Baseline in log\_10 tissue culture infective dose\_50 (TCID50/mL) and was summarized for each treatment group. The differences between the treatment groups were planned to be evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID50/mL were obtained at interval visits after treatment. As the study was terminated prematurely, no statistical testing was performed on these data.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo intramuscular injection	Peramivir n=49 Participants Single intramuscular injection of 300mg peramivir
To Evaluate Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. Day 9 - Change from baseline	-3.00 influenza viral titer - log10 TCID50/mL Interval -4.5 to -1.5	-3.25 influenza viral titer - log10 TCID50/mL Interval -4.5 to -0.75
To Evaluate Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. Baseline	3.75 influenza viral titer - log10 TCID50/mL Interval 1.75 to 5.0	3.75 influenza viral titer - log10 TCID50/mL Interval 1.5 to 5.0
To Evaluate Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. Day 3 - Change from baseline	-2.25 influenza viral titer - log10 TCID50/mL Interval -4.25 to -0.25	-2.75 influenza viral titer - log10 TCID50/mL Interval -4.25 to 1.0
To Evaluate Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. Day 5 - Change from baseline	-3.00 influenza viral titer - log10 TCID50/mL Interval -4.25 to -0.75	-3.00 influenza viral titer - log10 TCID50/mL Interval -4.5 to -1.0

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Peramivir

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=25 participants at risk Placebo intramuscular injection	Peramivir n=57 participants at risk Single intramuscular injection of 300mg peramivir
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	7.0% 4/57 • Number of events 4 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Gastrointestinal disorders Nausea	8.0% 2/25 • Number of events 2 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	7.0% 4/57 • Number of events 4 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Gastrointestinal disorders Vomiting	12.0% 3/25 • Number of events 3 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	7.0% 4/57 • Number of events 4 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Nervous system disorders Ageusia	0.00% 0/25 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	3.5% 2/57 • Number of events 2 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Nervous system disorders Dizziness	4.0% 1/25 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	7.0% 4/57 • Number of events 4 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Nervous system disorders Syncope Vasovagal	12.0% 3/25 • Number of events 3 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	0.00% 0/57 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
General disorders Injection Site Pain	4.0% 1/25 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	7.0% 4/57 • Number of events 4 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/25 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	5.3% 3/57 • Number of events 3 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Musculoskeletal and connective tissue disorders Muscle Spasms	4.0% 1/25 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	1.8% 1/57 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Investigations Urine Protein Present	4.0% 1/25 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	1.8% 1/57 • Number of events 1 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/25 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.	3.5% 2/57 • Number of events 2 • Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.

Additional Information

Study Director

BioCryst Pharmaceuticals Inc

Phone: +1 919-859-1302

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place