Influenza A
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGPimodivir 600 mg
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).
DRUGPlacebo
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).
OTHERSOC Treatment
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.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
13 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Tested positive for influenza A infection after the onset of symptoms using a polymerase chain reaction (PCR)-based or other rapid molecular diagnostic assay * Requires hospitalization to treat influenza infection and/or to treat complications of influenza infection (for example, radiological signs of lower respiratory tract disease, septic shock, central nervous system \[CNS\] involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, severe dehydration, myocarditis, pericarditis, ischemic heart disease, exacerbation of underlying chronic pulmonary disease, including asthma, chronic obstructive pulmonary disease \[COPD\], decompensation of previously controlled diabetes mellitus), including participants admitted to the Intensive Care Unit (ICU) * Enrollment and initiation of study drug treatment less than or equal to (\<=)96 hours after onset of influenza symptoms * Being on invasive mechanical ventilation or having a peripheral capillary oxygen saturation (SpO2) less than (\<)94 percent (%) on room air during screening. Participants with known pre-influenza SpO2 \<94% must have an SpO2 decline greater than or equal to (\>=)3% from pre-influenza SpO2 during screening * Having a screening/baseline National Early Warning Score 2 (NEWS2) of \>=4
Exclusion criteria
* Received more than 3 doses of influenza antiviral medication (for example, oseltamivir \[OST\] or zanamivir), or any dose of ribavarin (RBV) within 2 weeks, prior to first study drug intake. Received intravenous (IV) peramivir more than one day prior to screening * Unstable angina pectoris or myocardial infarction within 30 days prior to screening (inclusive) * Presence of clinically significant heart arrhythmias, uncontrolled, unstable atrial arrhythmia, or sustained ventricular arrhythmia, or risk factors for Torsade de Pointes syndrome * Known severe hepatic impairment (Child Pugh C cirrhosis) or chronic hepatitis C infection undergoing hepatitis C antiviral therapy * Severely immunocompromised in the opinion of the investigator (for example, known cluster of differentiation 4 plus \[CD4+\] count \<200 cells per cubic millimeter \[cells/mm\^3\], absolute neutrophil count \<750/mm\^3, first course of chemotherapy completed within 2 weeks prior to screening, history of stem cell transplant within 1 year prior to screening, any history of a lung transplant) * Known allergies, hypersensitivity, or intolerance to pimodivir or its excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hospital Recovery Scale on Day 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adjudicated Influenza Complications | Up to Day 33 | 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 \[for example, sinusitis and otitis\]). |
| Viral Load Over Time | Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14 and 19 | 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. |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Up to Day 33 | 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. |
| Number of Participants With Emergence of Viral Resistance to Pimodivir | Up to Day 33 | 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 to Hospital Discharge | Up to Day 33 | The time to hospital discharge was defined as the time from start of study drug to hospital discharge. |
| Number of Participants With Clinically Significant Changes in Laboratory Tests | Up to Day 33 | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | Up to Day 33 | Number of participants with clinically significant changes in Electrocardiogram (ECG) was reported. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Up to Day 33 | Number of participants with clinically significant changes in vital signs (temperature, pulse rate, respiratory rate and blood pressure) was reported. |
| Plasma Concentration of Pimodivir | 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 | Plasma concentration of Pimodivir was reported. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pimodivir + SOC Participants received 600 milligram (mg) Pimodivir twice daily (bid) on Day 1 through Day 5 along with standard of care (SOC) treatment. Eligible participants were given an optional treatment extension of 5 days bid. | 163 |
| Placebo + SOC Participants received matching placebo bid on Day 1 through Day 5 along with SOC treatment. Eligible participants were given an optional treatment extension of 5 days bid. | 163 |
| Total | 326 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 0 |
| Overall Study | Lost to Follow-up | 1 | 7 |
| Overall Study | Other | 5 | 1 |
| Overall Study | Randomized, not treated | 5 | 3 |
| Overall Study | Withdrawal by Subject | 8 | 14 |
Baseline characteristics
| Characteristic | Placebo + SOC | Total | Pimodivir + SOC |
|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 16.88 | 58.7 years STANDARD_DEVIATION 16.2 | 59.7 years STANDARD_DEVIATION 15.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 49 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 264 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 13 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 64 Participants | 34 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 16 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) White | 114 Participants | 227 Participants | 113 Participants |
| Region of Enrollment ARGENTINA | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment AUSTRALIA | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment AUSTRIA | 10 Participants | 18 Participants | 8 Participants |
| Region of Enrollment BELGIUM | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment BRAZIL | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment BULGARIA | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment CANADA | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment CHILE | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment FRANCE | 7 Participants | 9 Participants | 2 Participants |
| Region of Enrollment GERMANY | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment INDIA | 10 Participants | 18 Participants | 8 Participants |
| Region of Enrollment ISRAEL | 16 Participants | 36 Participants | 20 Participants |
| Region of Enrollment ITALY | 0 Participants | 4 Participants | 4 Participants |
| Region of Enrollment LATVIA | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment LITHUANIA | 3 Participants | 4 Participants | 1 Participants |
| Region of Enrollment MALAYSIA | 9 Participants | 21 Participants | 12 Participants |
| Region of Enrollment MEXICO | 5 Participants | 12 Participants | 7 Participants |
| Region of Enrollment NETHERLANDS | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment NEW ZEALAND | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment POLAND | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment SINGAPORE | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment SLOVAKIA | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment SOUTH AFRICA | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment SPAIN | 11 Participants | 24 Participants | 13 Participants |
| Region of Enrollment SWEDEN | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment TAIWAN | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment THAILAND | 10 Participants | 22 Participants | 12 Participants |
| Region of Enrollment TURKEY | 5 Participants | 8 Participants | 3 Participants |
| Region of Enrollment UKRAINE | 8 Participants | 14 Participants | 6 Participants |
| Region of Enrollment UNITED KINGDOM | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment UNITED STATES | 19 Participants | 36 Participants | 17 Participants |
| Region of Enrollment VIETNAM | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 75 Participants | 167 Participants | 92 Participants |
| Sex: Female, Male Male | 88 Participants | 159 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 163 | 0 / 163 |
| other Total, other adverse events | 81 / 163 | 82 / 163 |
| serious Total, serious adverse events | 13 / 163 | 15 / 163 |
Outcome results
Primary
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
Population: Intent-To-Treat infected (ITT-i) set includes all participants from the RAND analysis set who received at least 1 dose of study drug and had a confirmed infection with influenza A. Here, N (number of participants analyzed) defined as participants evaluable for this outcome measure. Here, n (number analyzed) is defined as participants analyzed for specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Not hospitalized | 73 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Non-ICU hospitalization, not requiring supplemental oxygen | 50 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Non-ICU hospitalization, requiring supplemental oxygen | 18 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Admitted to the ICU, not requiring invasive mechanical ventilation | 6 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Requiring invasive mechanical ventilation | 2 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Death | 3 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza less than or equal to (<=)72 hour (h): Not hospitalized | 61 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Non-ICU hospitalization, not requiring supplemental oxygen | 38 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Non-ICU hospitalization, requiring supplemental oxygen | 15 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Admitted to the ICU, not requiring invasive mechanical ventilation | 4 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Requiring invasive mechanical ventilation | 2 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Death | 2 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza greater than (>) 72h: Not hospitalized | 12 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Non-ICU hospitalization, not requiring supplemental oxygen | 12 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Non-ICU hospitalization, requiring supplemental oxygen | 3 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Admitted to the ICU, not requiring invasive mechanical ventilation | 2 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Requiring invasive mechanical ventilation | 0 Participants |
| Pimodivir + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Death | 1 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Non-ICU hospitalization, not requiring supplemental oxygen | 10 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Not hospitalized | 69 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Admitted to the ICU, not requiring invasive mechanical ventilation | 5 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Non-ICU hospitalization, not requiring supplemental oxygen | 42 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Death | 0 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Non-ICU hospitalization, requiring supplemental oxygen | 25 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Requiring invasive mechanical ventilation | 2 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Admitted to the ICU, not requiring invasive mechanical ventilation | 6 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Non-ICU hospitalization, requiring supplemental oxygen | 6 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Requiring invasive mechanical ventilation | 3 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Death | 0 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Any time since onset influenza: Death | 0 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Requiring invasive mechanical ventilation | 1 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza less than or equal to (<=)72 hour (h): Not hospitalized | 56 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza greater than (>) 72h: Not hospitalized | 13 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Non-ICU hospitalization, not requiring supplemental oxygen | 32 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza >72h: Admitted to the ICU, not requiring invasive mechanical ventilation | 1 Participants |
| Placebo + SOC | Number of Participants With Hospital Recovery Scale on Day 6 | Time since onset influenza <=72h: Non-ICU hospitalization, requiring supplemental oxygen | 19 Participants |
Secondary
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
Population: The Intent-To-Treat infected (ITT-i) set includes all participants from the RAND analysis set who received at least 1 dose of study drug and who had a confirmed infection with influenza A and were analyzed by planned treatment. Here, n (number analyzed) is defined as number of participants analyzed for specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pimodivir + SOC | Number of Participants With Adjudicated Influenza Complications | Any time since onset influenza | 28 Participants |
| Pimodivir + SOC | Number of Participants With Adjudicated Influenza Complications | Time since onset influenza <=72h | 24 Participants |
| Pimodivir + SOC | Number of Participants With Adjudicated Influenza Complications | Time since onset influenza >72h | 4 Participants |
| Placebo + SOC | Number of Participants With Adjudicated Influenza Complications | Any time since onset influenza | 29 Participants |
| Placebo + SOC | Number of Participants With Adjudicated Influenza Complications | Time since onset influenza <=72h | 24 Participants |
| Placebo + SOC | Number of Participants With Adjudicated Influenza Complications | Time since onset influenza >72h | 5 Participants |
Secondary
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 33
Population: The safety set (or all participants treated) includes all participants who received at least one dose of study drug and were analyzed by treatment arm as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimodivir + SOC | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 85 Participants |
| Placebo + SOC | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 84 Participants |
Secondary
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
Population: The safety set (or all participants treated) includes all participants who received at least one dose of study drug and were analyzed by treatment arm as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimodivir + SOC | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | 0 Participants |
| Placebo + SOC | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) | 0 Participants |
Secondary
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
Population: The safety set (or all participants treated) includes all participants who received at least one dose of study drug and were analyzed by treatment arm as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimodivir + SOC | Number of Participants With Clinically Significant Changes in Laboratory Tests | 0 Participants |
| Placebo + SOC | Number of Participants With Clinically Significant Changes in Laboratory Tests | 0 Participants |
Secondary
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
Population: The safety set (or all participants treated) includes all participants who received at least one dose of study drug and were analyzed by treatment arm as treated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pimodivir + SOC | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo + SOC | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
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
Population: Intent-To-Treat infected (ITT-i) set includes all participants from the RAND analysis set who received at least 1 dose of study drug and who had a confirmed infection with influenza A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pimodivir + SOC | Number of Participants With Emergence of Viral Resistance to Pimodivir | Neuraminidase (NA) region: With emerging mutations of interest | 0 Participants |
| Pimodivir + SOC | Number of Participants With Emergence of Viral Resistance to Pimodivir | Polymerase basic protein (PB) 2 region: With emerging mutations of interest | 2 Participants |
| Placebo + SOC | Number of Participants With Emergence of Viral Resistance to Pimodivir | Neuraminidase (NA) region: With emerging mutations of interest | 3 Participants |
| Placebo + SOC | Number of Participants With Emergence of Viral Resistance to Pimodivir | Polymerase basic protein (PB) 2 region: With emerging mutations of interest | 0 Participants |
Secondary
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
Population: The safety set (or all participants treated) includes all participants who received at least one dose of study drug and were analyzed by treatment arm as treated. Here, N (number of participants analyzed) defined as participants evaluable for this outcome measure. n (number analyzed) is defined as number of participants analyzed for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimodivir + SOC | Plasma Concentration of Pimodivir | Day 6: 12hours post dose | 938.2 Nanogram per milliliter (ng/mL) | Standard Deviation 1374.7 |
| Pimodivir + SOC | Plasma Concentration of Pimodivir | Day 1: 1 hour30minutes to 6 hours postdose | 1696.3 Nanogram per milliliter (ng/mL) | Standard Deviation 2298.4 |
| Pimodivir + SOC | Plasma Concentration of Pimodivir | Day 3: Pre-Dose | 854.3 Nanogram per milliliter (ng/mL) | Standard Deviation 898.3 |
| Pimodivir + SOC | Plasma Concentration of Pimodivir | Day 5: Pre-Dose | 940.3 Nanogram per milliliter (ng/mL) | Standard Deviation 1081.1 |
| Pimodivir + SOC | Plasma Concentration of Pimodivir | Day 5: 1 hour30minutes to 6 hours postdose | 3046.7 Nanogram per milliliter (ng/mL) | Standard Deviation 3860.5 |
Secondary
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
Population: The Intent-To-Treat infected (ITT-i) set includes all participants from the RAND (randomized participants with a randomization date time at or before the date time of first intake of study drug, or with a randomization date time and no study drug intake) analysis set who received at least 1 dose of study drug and who had a confirmed infection with influenza A and were analyzed by planned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pimodivir + SOC | Time to Hospital Discharge | 113 hours |
| Placebo + SOC | Time to Hospital Discharge | 108 hours |
Secondary
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
Population: Intent-To-Treat infected (ITT-i) set includes all participants from the RAND analysis set who received at least 1 dose of study drug and who had a confirmed infection with influenza A. Here, N (number of participants analyzed) defined as participants evaluable for this outcome measure. n (number analyzed) is defined as number of participants analyzed for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimodivir + SOC | Viral Load Over Time | Day 7 | 2.103 Log 10 viral particles per milliliter | Standard Deviation 0.035 |
| Pimodivir + SOC | Viral Load Over Time | Day 4 | 3.460 Log 10 viral particles per milliliter | Standard Deviation 1.4952 |
| Pimodivir + SOC | Viral Load Over Time | Day 8 | 2.386 Log 10 viral particles per milliliter | Standard Deviation 0.7052 |
| Pimodivir + SOC | Viral Load Over Time | Day 1 | 5.433 Log 10 viral particles per milliliter | Standard Deviation 1.3102 |
| Pimodivir + SOC | Viral Load Over Time | Day 9 | 2.050 Log 10 viral particles per milliliter | Standard Deviation 0 |
| Pimodivir + SOC | Viral Load Over Time | Day 5 | 3.133 Log 10 viral particles per milliliter | Standard Deviation 1.35 |
| Pimodivir + SOC | Viral Load Over Time | Day 10 | 2.287 Log 10 viral particles per milliliter | Standard Deviation 0.6518 |
| Pimodivir + SOC | Viral Load Over Time | Day 3 | 3.913 Log 10 viral particles per milliliter | Standard Deviation 1.4202 |
| Pimodivir + SOC | Viral Load Over Time | Day 11 | 2.050 Log 10 viral particles per milliliter | — |
| Pimodivir + SOC | Viral Load Over Time | Day 14 | 2.137 Log 10 viral particles per milliliter | Standard Deviation 0.4163 |
| Pimodivir + SOC | Viral Load Over Time | Day 6 | 2.552 Log 10 viral particles per milliliter | Standard Deviation 0.71 |
| Pimodivir + SOC | Viral Load Over Time | Day 19 | 2.050 Log 10 viral particles per milliliter | Standard Deviation 0 |
| Pimodivir + SOC | Viral Load Over Time | Baseline | 5.657 Log 10 viral particles per milliliter | Standard Deviation 1.4693 |
| Pimodivir + SOC | Viral Load Over Time | Day 2 | 4.561 Log 10 viral particles per milliliter | Standard Deviation 1.5133 |
| Placebo + SOC | Viral Load Over Time | Day 19 | 2.050 Log 10 viral particles per milliliter | Standard Deviation 0 |
| Placebo + SOC | Viral Load Over Time | Baseline | 5.655 Log 10 viral particles per milliliter | Standard Deviation 1.4117 |
| Placebo + SOC | Viral Load Over Time | Day 1 | 6.410 Log 10 viral particles per milliliter | Standard Deviation 0.7826 |
| Placebo + SOC | Viral Load Over Time | Day 2 | 4.794 Log 10 viral particles per milliliter | Standard Deviation 1.4154 |
| Placebo + SOC | Viral Load Over Time | Day 3 | 4.057 Log 10 viral particles per milliliter | Standard Deviation 1.3425 |
| Placebo + SOC | Viral Load Over Time | Day 4 | 3.634 Log 10 viral particles per milliliter | Standard Deviation 1.2207 |
| Placebo + SOC | Viral Load Over Time | Day 5 | 3.157 Log 10 viral particles per milliliter | Standard Deviation 1.1112 |
| Placebo + SOC | Viral Load Over Time | Day 6 | 2.876 Log 10 viral particles per milliliter | Standard Deviation 0.975 |
| Placebo + SOC | Viral Load Over Time | Day 7 | 2.269 Log 10 viral particles per milliliter | Standard Deviation 0.3829 |
| Placebo + SOC | Viral Load Over Time | Day 8 | 2.463 Log 10 viral particles per milliliter | Standard Deviation 0.7051 |
| Placebo + SOC | Viral Load Over Time | Day 9 | 2.611 Log 10 viral particles per milliliter | Standard Deviation 0.8281 |
| Placebo + SOC | Viral Load Over Time | Day 10 | 2.346 Log 10 viral particles per milliliter | Standard Deviation 0.6357 |
| Placebo + SOC | Viral Load Over Time | Day 14 | 2.116 Log 10 viral particles per milliliter | Standard Deviation 0.2109 |