Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of IV Peramivir in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Influenza (NCT NCT00958776)

Last Updated: 2015-02-12

Results Overview

Time to clinical resolution was defined as the time in hours from initiation of study treatment until normalization of at least 4 of the 5 signs within the respective normalization criteria, maintained for at least 24-hours. Time to clinical resolution was summarized by treatment group using the method of Kaplan-Meier. For subjects who did not experience clinical resolution, values were censored at the date of their last non-missing assessment of clinical resolution during the study (whether this assessment occurred as an inpatient or as an outpatient).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

405 participants

Primary outcome timeframe

10 days

Results posted on

2015-02-12

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo+SOC Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Overall Study STARTED	137	268
Overall Study COMPLETED	121	239
Overall Study NOT COMPLETED	16	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo+SOC Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Overall Study Adverse Event	0	1
Overall Study Physician Decision	1	0
Overall Study Lost to Follow-up	2	6
Overall Study Withdrawal by Subject	7	16
Overall Study Protocol Violation	1	1
Overall Study Death	2	1
Overall Study Noncompliance; Protocol Deviations	2	3
Overall Study Missing	1	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of IV Peramivir in Addition to Standard of Care Compared to Standard of Care Alone in Adults and Adolescents Who Are Hospitalized Due to Influenza

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo+SOC n=137 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=268 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Total n=405 Participants Total of all reporting groups
Absolute Lymphocyte Count at Baseline	1.3 cell count STANDARD_DEVIATION 1.25 • n=5 Participants	1.3 cell count STANDARD_DEVIATION 1.52 • n=7 Participants	1.3 cell count STANDARD_DEVIATION 1.44 • n=5 Participants
Chest X-ray at Screening Normal	88 participants n=5 Participants	148 participants n=7 Participants	236 participants n=5 Participants
Chest X-ray at Screening Abnormal	49 participants n=5 Participants	120 participants n=7 Participants	169 participants n=5 Participants
ICU admission at Baseline Not admitted	117 participants n=5 Participants	231 participants n=7 Participants	348 participants n=5 Participants
ICU admission at Baseline Missing	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Age, Continuous	43 years n=5 Participants	47 years n=7 Participants	46 years n=5 Participants
Age, Customized Children 6-11 Years	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Age, Customized Adolescents 12-17 Years	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Age, Customized Adults 18-24 Years	23 participants n=5 Participants	33 participants n=7 Participants	56 participants n=5 Participants
Age, Customized Adults 25-34 Years	23 participants n=5 Participants	40 participants n=7 Participants	63 participants n=5 Participants
Influenza Vaccination Status Not vaccinated this year	111 participants n=5 Participants	226 participants n=7 Participants	337 participants n=5 Participants
Influenza Vaccination Status Vaccinated this year	26 participants n=5 Participants	41 participants n=7 Participants	67 participants n=5 Participants
Influenza Vaccination Status Missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Duration of Illness ≤ 48 hours	75 participants n=5 Participants	150 participants n=7 Participants	225 participants n=5 Participants
Duration of Illness > 48 hours	62 participants n=5 Participants	118 participants n=7 Participants	180 participants n=5 Participants
Standard of Care Received (CRF) NAI-Containing Antiviral Therapy	89 participants n=5 Participants	179 participants n=7 Participants	268 participants n=5 Participants
Standard of Care Received (CRF) Non-NAI-Containing Antiviral Therapy	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Standard of Care Received (CRF) Supportive Care/No Antiviral Therapy	39 participants n=5 Participants	82 participants n=7 Participants	121 participants n=5 Participants
Age, Customized Adults 35-44 Years	21 participants n=5 Participants	44 participants n=7 Participants	65 participants n=5 Participants
Age, Customized Adults 45-54 Years	27 participants n=5 Participants	44 participants n=7 Participants	71 participants n=5 Participants
Age, Customized Adults 55-64 Years	17 participants n=5 Participants	45 participants n=7 Participants	62 participants n=5 Participants
Age, Customized Adults 65-74 Years	11 participants n=5 Participants	25 participants n=7 Participants	36 participants n=5 Participants
Age, Customized Adults ≥ 75 Years	9 participants n=5 Participants	28 participants n=7 Participants	37 participants n=5 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	132 Participants n=7 Participants	199 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	136 Participants n=7 Participants	206 Participants n=5 Participants
Race/Ethnicity, Customized Asian	31 participants n=5 Participants	52 participants n=7 Participants	83 participants n=5 Participants
Race/Ethnicity, Customized White	71 participants n=5 Participants	169 participants n=7 Participants	240 participants n=5 Participants
Race/Ethnicity, Customized Black, of African Heritage or African American	23 participants n=5 Participants	28 participants n=7 Participants	51 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	11 participants n=5 Participants	18 participants n=7 Participants	29 participants n=5 Participants
Body mass index (BMI)	27.7 kg/m^2 n=5 Participants	27.5 kg/m^2 n=7 Participants	27.6 kg/m^2 n=5 Participants
Supplemental oxygen required at Screening Needed	45 participants n=5 Participants	87 participants n=7 Participants	132 participants n=5 Participants
Supplemental oxygen required at Screening Not needed	89 participants n=5 Participants	177 participants n=7 Participants	266 participants n=5 Participants
Supplemental oxygen required at Screening Missing	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
ICU admission at Baseline Admitted	17 participants n=5 Participants	33 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 10 days

Population: The Intent-to-Treat Infected-Non-NAI-Containing SOC (ITTI-Non-NAI) population included randomized subjects who received at least 1 dose of study drug, had confirmed influenza, and who received an SOC that does not contain a NAI at randomization.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Time to Clinical Resolution (Kaplan-Meier Estimate)	49.5 hours Interval 40.0 to 61.9	42.5 hours Interval 34.0 to 57.9

SECONDARY outcome

Timeframe: Baseline and 24, 48, 108 hours

The reduction in viral shedding was assessed as the change from baseline in log10 tissue culture infective dose50 (TCID50/mL) and RT-PCR and was summarized for each treatment group and study visit.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=34 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=61 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Change (Reduction) in Influenza Virus Titer Change from Baseline, 48 Hours	-1.67 log10 viral particles/mL Interval -2.14 to -0.87	-2.02 log10 viral particles/mL Interval -2.49 to -1.46
Change (Reduction) in Influenza Virus Titer Change from Baseline, 108 Hours	-2.39 log10 viral particles/mL Interval -3.29 to -1.59	-2.48 log10 viral particles/mL Interval -3.05 to -2.11
Change (Reduction) in Influenza Virus Titer Change from Baseline, 24 Hours	-1.09 log10 viral particles/mL Interval -1.62 to -0.8	-1.49 log10 viral particles/mL Interval -1.84 to -1.22

SECONDARY outcome

Timeframe: 10 days

Time to alleviation of clinical symptoms of influenza was measured as the time from the first dose of study drug through the time period in which all 7 symptoms of influenza (cough, sore throat, nasal congestion, myalgia \[aches and pains\], headache, feverishness, and fatigue) were absent or rated as no greater than mild for at least 24 hours. Time to alleviation of symptoms was estimated using the method of Kaplan-Meier. Subjects who did not have resolution of any individual clinical sign were censored at the time of their last non-missing assessment of that sign.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=77 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Time to Alleviation of Clinical Symptoms of Influenza	68.2 hours Interval 63.0 to 86.0	67.0 hours Interval 59.0 to 78.8

SECONDARY outcome

Timeframe: 10 days

Time to resolution of fever was measured as the time from initiation of study treatment until resolution of fever, maintained for at least 24 hours; temperature measurements taken less than 4 hours after antipyretic use were treated as missing values.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Time to Resolution of Fever (Kaplan-Meier Estimate)	41.0 hours Interval 28.0 to 58.9	42.5 hours Interval 32.0 to 56.4

SECONDARY outcome

Timeframe: 10 days

Time to resumption of usual activities was determined from the visual analog scale (scale ranged from 0 to 10 where 0 indicated subject was unable to perform usual activities at all and 10 indicated subject was able to perform all usual activities fully). Time to resumption of usual activities was summarized by treatment group using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=42 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=74 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Time to Resumption of Usual Activities	9.3 days Interval 7.1 to 12.8	8.1 days Interval 5.1 to 9.3

SECONDARY outcome

Timeframe: 10 days

The number of subjects requiring ICU admission post-randomization was summarized by treatment group.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Number of Subjects With ICU Admission After initiation of treatment	1 participants	0 participants
Number of Subjects With ICU Admission At any time	9 participants	15 participants
Number of Subjects With ICU Admission At Baseline	8 participants	15 participants

SECONDARY outcome

Timeframe: 10 days

Duration of postbaseline ICU admission was defined as the total number of days in the ICU for those subjects who had a post-baseline admission to the ICU. Only days starting after the initial postbaseline admission were included. If a subject's stay in the ICU was ongoing, the duration was censored at the last study visit. Subjects who did not have a postbaseline admission had a duration of 0.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Duration of All ICU Admissions (Kaplan-Meier Estimate)	3.0 days Interval 2.0 to 6.0	3.0 days Interval 3.0 to 4.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 days

Time to hospital discharge, defined as the number of days from initiation of study treatment until the subject was discharged from the hospital, was summarized by treatment group using the method of Kaplan-Meier. Subjects who were not discharged from the hospital were censored at their last study visit.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Time to Hospital Discharge	5.0 days Interval 5.0 to 6.0	5.0 days The number of observed events was too small to allow estimation of the required parameter.

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 days

Influenza-related complications were defined as the occurrence of sinusitis, otitis, bronchitis, and pneumonia as reported on the influenza-related complications CRF.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Incidence of Influenza-Related Complications Any Influenza-Related Complication	9 participants	15 participants
Incidence of Influenza-Related Complications Otitis	0 participants	0 participants
Incidence of Influenza-Related Complications Sinusitis	1 participants	2 participants
Incidence of Influenza-Related Complications Bronchitis	4 participants	5 participants
Incidence of Influenza-Related Complications Pneumonia	4 participants	8 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 days

Subjects who had not met the protocol-defined criteria of clinical resolution on Day 5 or who had detectable virus by RT-PCR from a sample collected on Study Day 4 after dosing continued their assigned treatment for a further 5 days.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=43 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=78 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Number of Subjects Requiring More Than 5 Days of Study Drug	3 participants	6 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Survival was calculated as the number of days from initiation of study drug until death or last contact. Estimates and 95% confidence intervals were calculated using the method of Kaplan-Meier and presented by treatment group.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=42 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=72 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate) 14 Day Survival	98 Percent Survival Interval 84.0 to 100.0	100 Percent Survival Interval 100.0 to 100.0
Survival at 14 and 28 Days After Initiation of Study Drug (Kaplan-Meier Estimate) 28 Day Survival	98 Percent Survival Interval 84.0 to 100.0	100 Percent Survival Interval 100.0 to 100.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Initial (baseline or post-baseline) and up to 10 days

Population: The Intent-to-Treat Infected (ITTI) population included randomized subjects who received at least 1 dose of study drug, and had confirmed influenza A or B.

Initial viral sensitivity to peramivir, oseltamivir, and zanamivir was assessed over time during the study, and was presented by influenza virus subtype. Initial assessment of susceptibility may have occurred at a post-baseline visit.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=116 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=222 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) A: H3N2-Initial Peramivir Susceptibility	0.18 nM Standard Deviation 0.074	0.18 nM Standard Deviation 0.044
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) A: H3N2-Initial Oseltamivir Susceptibility	0.30 nM Standard Deviation 0.131	0.31 nM Standard Deviation 0.131
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) A: H3N2-Initial Zanamivir Susceptibility	0.34 nM Standard Deviation 0.185	0.34 nM Standard Deviation 0.071
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) A: H1N1- Initial Peramivir Susceptibility	0.24 nM Standard Deviation 0.152	1.11 nM Standard Deviation 6.181
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) A: H1N1- Initial Oseltamivir Susceptibility	1.12 nM Standard Deviation 0.772	11.03 nM Standard Deviation 70.524
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) A: H1N1- Initial Zanamivir Susceptibility	0.60 nM Standard Deviation 0.416	0.60 nM Standard Deviation 0.402
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) B: Initial Peramivir Susceptibility	1.14 nM Standard Deviation 0.625	1.15 nM Standard Deviation 0.628
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) B: Initial Oseltamivir Susceptibility	18.47 nM Standard Deviation 4.830	21.47 nM Standard Deviation 9.422
Initial Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; IC50 (nM) B: Initial Zanamivir Susceptibility	2.36 nM Standard Deviation 1.009	2.30 nM Standard Deviation 0.958

OTHER_PRE_SPECIFIED outcome

Timeframe: Initial (baseline or post-baseline) and up to 10 days

Population: The Intent-to-Treat Infected (ITTI) population included randomized subjects who received at least 1 dose of study drug, and had confirmed influenza A or B.

Viral sensitivity to peramivir, oseltamivir, and zanamivir was assessed over time during the study, and was presented as fold change from initial sensitivity by influenza virus subtype. Initial assessment of susceptibility may have occurred at a post-baseline visit.

Outcome measures

Outcome measures
Measure	Placebo+SOC n=116 Participants Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=222 Participants Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial A: H3N2-Fold Change in Oseltamivir Susceptibility	1.36 fold change Standard Deviation 0.836	1.14 fold change Standard Deviation 0.805
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial A: H3N2-Fold Change in Zanamivir Susceptibility	2.70 fold change Standard Deviation 6.563	1.33 fold change Standard Deviation 0.773
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial A: H1N1-Fold Change in Peramivir Susceptibility	1.12 fold change Standard Deviation 0.879	3.63 fold change Standard Deviation 16.333
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial A: H1N1-Fold Change in Oseltamivir Susceptibility	1.51 fold change Standard Deviation 1.695	9.20 fold change Standard Deviation 50.920
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial A: H1N1-Fold Change in Zanamivir Susceptibility	1.03 fold change Standard Deviation 0.728	1.06 fold change Standard Deviation 0.490
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial B: Fold Change in Peramivir Susceptibility	1.01 fold change Standard Deviation 0.331	3.21 fold change Standard Deviation 8.456
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial B: Fold Change in Zanamivir Susceptibility	1.02 fold change Standard Deviation 0.375	1.36 fold change Standard Deviation 0.613
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial A: H3N2-Fold Change in Peramivir Susceptibility	1.23 fold change Standard Deviation 0.555	1.19 fold change Standard Deviation 0.527
Change in Viral Sensitivity to Peramivir, Oseltamivir, and Zanamivir; Fold Change From Initial B: Fold Change in Oseltamivir Susceptibility	0.98 fold change Standard Deviation 0.376	1.48 fold change Standard Deviation 1.635

Adverse Events

Placebo+SOC

Serious events: 13 serious events

Other events: 42 other events

Deaths: 0 deaths

Peramivir+SOC

Serious events: 15 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

William P. Sheridan, MBBS

BioCryst Pharmaceuticals, Inc.

Phone: 919-859-1302

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo+SOC n=134 participants at risk Placebo Peramivir (BCX1812) administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.	Peramivir+SOC n=264 participants at risk Adults (≥ 18 years): Peramivir (BCX-1812) 600 mg, administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care. Adolescents (12-17 years): Peramivir (BCX-1812) 10 mg/kg (not to exceed a maximum dose of 600 mg), administered intravenously, once daily (every 24 hrs) for 5 days (5 doses) in addition to institution's standard of care.
Gastrointestinal disorders Diarrhoea	7.5% 10/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	4.5% 12/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Gastrointestinal disorders Nausea	7.5% 10/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	3.8% 10/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Gastrointestinal disorders Constipation	5.2% 7/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	2.3% 6/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Gastrointestinal disorders Vomiting	3.7% 5/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	1.1% 3/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Psychiatric disorders Insomnia	0.75% 1/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	3.8% 10/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Psychiatric disorders Anxiety	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	1.9% 5/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Investigations Alanine Aminotransferase Increased	3.7% 5/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	2.7% 7/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Investigations Blood Creatine Phosphokinase Increased	0.75% 1/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	2.7% 7/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Investigations Aspartate Aminotransferase Increased	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	2.3% 6/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Investigations Blood Glucose Increased	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	1.9% 5/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Metabolism and nutrition disorders Hypokalaemia	3.7% 5/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	3.0% 8/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Metabolism and nutrition disorders Hypophosphataemia	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	0.76% 2/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Metabolism and nutrition disorders Dehydration	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	0.38% 1/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Metabolism and nutrition disorders Hypomagnesaemia	3.0% 4/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	0.38% 1/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Nervous system disorders Headache	1.5% 2/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	2.7% 7/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Nervous system disorders Dizziness	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	0.38% 1/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Vascular disorders Hypertension	0.75% 1/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	2.7% 7/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Blood and lymphatic system disorders Anaemia	2.2% 3/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	1.9% 5/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).
Respiratory, thoracic and mediastinal disorders Epistaxis	3.0% 4/134 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).	1.5% 4/264 • Adverse events were recorded at least once daily during the period of study drug administration in the hospital and at each follow-up visit until the study completion visit at Day 14 or later. For subjects who experienced the same coded event more than once, only one event is presented. Seven of the 405 subjects who were randomized did not receive study drug; safety analyses included 398 subjects (134 in the Placebo+SOC arm and 264 in the Peramivir+SOC arm).