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, adult, and elderly hospitalized participants with influenza A infection. The study will be conducted in 3 phases: screening phase, double-blind treatment period of 5 days (with the possibility to extend treatment period by 5 days for participants who will enter an optional double-blind extension treatment arm), and post treatment follow-up period of 23 days. Study evaluations will include efficacy, pharmacokinetic, biomarkers, safety and tolerability. The duration of participation in study for each participant is 28 days, except for participants receiving extended treatment, for whom study duration will be up to 33 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
334
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 who meet treatment extension criteria may receive an additional 5 day course of the same treatment as received at study start (on Days 6 through 10).
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 who meet treatment extension criteria may receive an additional 5 day course of the same treatment as received at study start (on Days 6 through 10).
Number of Participants With Hospital Recovery Scale on Day 6
The hospital recovery scale assesses a participant's clinical status. The scale provides 6 mutually exclusive conditions ordered from best to worst: 1) not hospitalized; 2) non-ICU hospitalization, not requiring supplemental oxygen; 3) non-ICU hospitalization, requiring supplemental oxygen; 4) admitted to the ICU, not requiring invasive mechanical ventilation; 5) requiring invasive mechanical ventilation; and 6) death.
Time frame: Day 6
Time to Hospital Discharge
The time to hospital discharge was defined as the time from start of study drug to hospital discharge.
Time frame: Up to Day 33
Number of Participants With Adjudicated Influenza Complications
Influenza complications include pulmonary complications (such as respiratory failure, primary viral pneumonia, secondary bacterial pneumonia \[including pneumonia attributable to unusual pathogens\], exacerbations of chronic underlying pulmonary diseases such as chronic obstructive pulmonary disease \[COPD\] and asthma) and extrapulmonary complications (such as cardiovascular and cerebrovascular diseases \[for example, myocardial infarction, congestive heart failure, arrhythmia, stroke\], muscular disorders \[for example, myositis, rhabdomyolysis\], central nervous system \[CNS\] involvement, acute exacerbation of chronic kidney disease, decompensation of previously controlled diabetes mellitus, other infections \[for example, sinusitis and otitis\]).
Time frame: Up to Day 33
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, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14 and 19
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
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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 started no later than the day when participants initially receive pimodivir. An influenza antiviral as part of the SOC cannot be changed (for example, switching one influenza antiviral for another) during either the treatment period or extension phase, with the exception that an influenza antiviral may be discontinued in the case of a suspected AE.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Nea Baptist Clinic
Jonesboro, Arkansas, United States
UCSF Fresno
Fresno, California, United States
Miller Children's at Long Beach Medical Center
Long Beach, California, United States
Stanford University School of Medicine
Stanford, California, United States
Destin Pulmonary Critical Care, PLLS.
Santa Rosa Beach, Florida, United States
Northside Hospital
Atlanta, Georgia, United States
Augusta University
Augusta, Georgia, United States
Anne Arundel Medical Center
Annapolis, Maryland, United States
University Of Maryland Medical Center
Baltimore, Maryland, United States
...and 259 more locations
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 33
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 33
Plasma Concentration of Pimodivir
Plasma concentration of Pimodivir was reported.
Time frame: Day 1: 1 hour30minutes to 6 hours postdose, Day 3: Predose, Day 5: Predose and 1 hour30minutes to 6 hours postdose, Day 6: 12 hours postdose
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 were collected at predefined time points for clinical laboratory testing.
Time frame: Up to Day 33
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
Number of participants with clinically significant changes in Electrocardiogram (ECG) was reported.
Time frame: Up to Day 33
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) was reported.
Time frame: Up to Day 33