The purpose of this study is to evaluate the clinical and virologic benefit of pimodivir in combination with Standard-of-Care (SOC) treatment compared to placebo in combination with SOC treatment.
This double-blind (neither researchers nor participants know what treatment participant is receiving) study will evaluate efficacy/safety of pimodivir in combination with SOC treatment versus placebo in combination with SOC treatment in adolescent (13 to 17 years), adult (18 to 65 years), and elderly (greater than \[\>\] 65 but less than or equal to \[\<=\] 85 years) non-hospitalized participants with influenza A infection who are at risk of developing complications. The study will be conducted in 3 phases: screening phase, double-blind treatment period (5 days), a post treatment follow-up period (23 days). Study evaluations include efficacy, clinical and virological outcomes, pharmacokinetics (PK), PK/pharmacodynamics, biomarkers, safety and tolerability. The duration of participation in the study for each participant is 28 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
553
Participants will receive pimodivir 600 mg, orally, twice daily, for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of pimodivir on Day 1 \[evening\], dosing will continue until the morning of Day 6).
Participants will receive placebo matching to pimodivir, orally twice daily for 5 days (on Days 1 through 5; for participants who will receive only 1 dose of placebo on Day 1 \[evening\], dosing will continue until the morning of Day 6).
Participants may receive SOC treatment as a part of background therapy. The SOC treatment is determined by the investigator based on local practice, and may include influenza antivirals and/or supportive care only. The choice to use influenza antivirals as part of the SOC should be made before randomization. The influenza antiviral should be started no later than Day 2 morning (up to noon).
Time to Resolution of 7 Primary Influenza-related Symptoms as Assessed by the Patient-Reported Outcome (PRO) Measure Flu-Intensity and Impact Questionnaire (Flu-iiQ)
The Flu-iiQ is a PRO that measures influenza symptom intensity (none, mild, moderate, or severe) on a 4 point Likert response rating scale ranging from 0 to 3, where "0" represents the absence of symptom and "3" represents the severe symptom. The resolution of influenza-related symptoms is defined as the beginning of the 24-hour period that 7 influenza symptoms (cough, sore throat, headache, nasal congestion, feeling feverish, body aches and pains, fatigue) are at most mild or at least back to previous level of symptom severity in case the participant reported the symptom as pre-existing.
Time frame: Up to Day 28
Number of Participants Hospitalized After Treatment Initiation
The number of participants hospitalized after treatment initiation were reported.
Time frame: Up to Day 28
Viral Load Over Time
Viral load over time was measured by quantitative real time polymerase chain reaction (qRT-PCR) and viral culture in the mid-turbinate (MT) nasal swabs and endotracheal samples.
Time frame: Baseline, Day 3, 6, 10, 14
Number of Participants With Emergence of Viral Resistance to Pimodivir
Emergence of viral resistance to pimodivir was detected by genotyping and/or phenotyping. Nasal MT swabs and endotracheal samples were used for sequence analysis of the polymerase basic protein (PB)2 region of the influenza polymerase gene, and of neuraminidase (NA) genes for participants using an NA inhibitor (NAI) as part of their Standard of Care (SOC).
Time frame: Up to Day 28
Plasma Concentration of Pimodivir
Plasma concentration of Pimodivir was reported.
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Alabama Clinical Therapeutics, LLC
Birmingham, Alabama, United States
Cahaba Research Inc
Birmingham, Alabama, United States
Scottsboro Quick Care Clinic
Scottsboro, Alabama, United States
SC Clinical Research Inc.
California City, California, United States
Research Center of Fresno Inc
Fresno, California, United States
Allied Clinical Research
Gold River, California, United States
Innovative Clinical Research Inc
Harbor City, California, United States
Om Research LLC
Lancaster, California, United States
Ark Clinical Research
Long Beach, California, United States
...and 417 more locations
Time frame: Day 3, 6, 7
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Up to Day 28
Number of Participants With Clinically Significant Changes in Laboratory Tests
Number of participants with clinically significant changes in laboratory tests were reported. Blood samples for hematology, serum chemistry, and urinalysis was collected at predefined time points for clinical laboratory testing.
Time frame: Up to Day 28
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
Number of participants with clinically significant changes in Electrocardiogram (ECG) were reported.
Time frame: Up to Day 28
Number of Participants With Clinically Significant Changes in Vital Signs
Number of participants with clinically significant changes in vital signs (temperature, pulse rate, respiratory rate and blood pressure) were reported.
Time frame: Up to Day 28