This multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study will evaluate the efficacy and safety of peramivir inhalation solution in adults with uncomplicated influenza. Approximately 600 participants aged 18 to 64 years with laboratory-confirmed influenza and symptom onset within 48 hours will be randomized in a 2:1 ratio to receive a single nebulized dose of peramivir inhalation solution 80 mg or matching placebo. The primary efficacy outcome is the time to alleviation of all seven influenza symptoms. Secondary outcomes include changes in influenza viral RNA and infectious viral titers, time to viral clearance, alleviation of respiratory and systemic symptoms, resolution of fever, influenza-related complications, and use of rescue medication. Safety will be assessed through adverse events, clinical laboratory tests, vital signs, physical examinations, and electrocardiograms. Pharmacokinetics will also be evaluated in a subset of approximately 90 participants. Participants will be followed for approximately 15 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
600
Participants will receive a single nebulized dose of matching placebo on Day 1. The placebo will be administered as two 2-mL ampules containing no active peramivir. Nebulization will last at least 15 minutes. Participants will remain under observation at the study site for 30 minutes after completion of administration.
Participants will receive a single nebulized administration of matching placebo on Day 1. Two 2-mL placebo ampules containing no active peramivir will be placed in the nebulizer, for a total volume of 4 mL. Nebulization will last at least 15 minutes. Participants will remain under observation at the study site for 30 minutes after completion of administration.
China-Japan Friendship Hospital
Beijing, Beijing Municipality, China
Time to Alleviation of All Influenza Symptoms
Time in hours from initiation of study treatment to alleviation of all seven influenza symptoms recorded in the participant diary. The seven symptoms are nasal congestion, sore throat, cough, muscle or joint pain, fatigue, headache, and feverishness or chills. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all seven symptoms, maintained for at least 21.5 hours.
Time frame: From initiation of study treatment through 336 hours after treatment
Change From Baseline in Influenza Virus RNA and Viral Titer
Change from baseline in influenza virus RNA measured by quantitative PCR (qPCR; log10 copies/mL) and influenza viral titer (log10 TCID50/mL) at scheduled visits.
Time frame: Baseline (pre-dose), Days 2, 3, 4, 5, Day 9 ± 2 days, and Day 15 (+3 days)/early withdrawal.
Weighted Time to Alleviation of Five Core Influenza Symptoms
Weighted time in hours from initiation of study treatment to alleviation of all five core influenza symptoms: feverishness or chills, cough, nasal congestion, sore throat, and headache. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all five symptoms, maintained for at least 21.5 hours. Symptom-specific weights will be applied as prespecified in the statistical analysis plan.
Time frame: From initiation of study treatment through 336 hours after treatment
Time to Influenza Viral RNA Negativity
Time in hours from initiation of study treatment to the first respiratory specimen in which influenza viral RNA is below the assay limit of detection, as measured by quantitative polymerase chain reaction.
Time frame: From initiation of study treatment through Day 15 (+3 days)
Time to Influenza Virus Titer Negativity
Time in hours from initiation of study treatment to the first respiratory specimen in which the infectious influenza virus titer is below the assay lower limit of quantification.
Time frame: From initiation of study treatment through Day 15 (+3 days)
Proportion of Participants With Influenza Virus RNA Below the LOD and Viral Titer Below the LLOQ
Proportion of participants with influenza virus RNA below the qPCR LOD and influenza viral titer below the LLOQ at each scheduled visit.
Time frame: Baseline, Days 2, 3, 4, 5, Day 9 ± 2 days, and Day 15 (+3 days)/early withdrawal.
Percentage of Participants With Alleviation of All Influenza Symptoms
Percentage of participants with scores of 0 (absent) or 1 (mild) for all seven influenza symptoms, maintained for at least 21.5 hours.
Time frame: Assessed repeatedly from initiation of study treatment through 336 hours after treatment
Percentage of Participants With Alleviation of All Respiratory Symptoms
Percentage of participants with scores of 0 (absent) or 1 (mild) for all three respiratory symptoms-nasal congestion, sore throat, and cough-maintained for at least 21.5 hours.
Time frame: Assessed repeatedly from initiation of study treatment through 336 hours after treatment
Time to Alleviation of All Respiratory Symptoms
Time in hours from initiation of study treatment to alleviation of nasal congestion, sore throat, and cough. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all three symptoms, maintained for at least 21.5 hours.
Time frame: From initiation of study treatment through 336 hours after treatment
Percentage of Participants With Alleviation of All Systemic Symptoms
Percentage of participants with scores of 0 (absent) or 1 (mild) for all four systemic symptoms-muscle or joint pain, fatigue, headache, and feverishness or chills-maintained for at least 21.5 hours.
Time frame: Assessed repeatedly from initiation of study treatment through 336 hours after treatment
Time to Alleviation of All Systemic Symptoms
Time in hours from initiation of study treatment to alleviation of muscle or joint pain, fatigue, headache, and feverishness or chills. Alleviation is defined as a score of 0 (absent) or 1 (mild) for all four symptoms, maintained for at least 21.5 hours.
Time frame: From initiation of study treatment through 336 hours after treatment
Time to Alleviation of Each Individual Influenza Symptom
Time in hours from initiation of study treatment to alleviation of each of the seven influenza symptoms, assessed separately: nasal congestion, sore throat, cough, muscle or joint pain, fatigue, headache, and feverishness or chills. Alleviation is defined as a score of 0 (absent) or 1 (mild), maintained for at least 21.5 hours.
Time frame: From initiation of study treatment through 336 hours after treatment
Time to Alleviation of Fever
Time in hours from initiation of study treatment to the first axillary temperature below 37.0°C that is maintained for at least 12 hours.
Time frame: From initiation of study treatment through 336 hours after treatment
Percentage of Participants With Normalization of Body Temperature
Percentage of participants with an axillary temperature below 37.0°C that is maintained for at least 12 hours.
Time frame: At 24, 48, 72, 96, 120, 144, and 168 hours after initiation of study treatment
Percentage of Participants With Influenza-Related Complications
Percentage of participants experiencing one or more influenza-related complications, including hospitalization, death, sinusitis, bronchitis, otitis media, or radiographically confirmed pneumonia.
Time frame: From initiation of study treatment through Day 15 (+3 days)
Use of Acetaminophen for Influenza-Related Symptoms
Proportion of participants using acetaminophen and frequency of acetaminophen use during the study treatment period.
Time frame: From initiation of study treatment through 336h.
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