Evaluation of Efficacy and Safety of Peramivir in Adults With Acute Serious or Potentially Life-threatening Influenza

• Sponsor: BioCryst Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00453999
• Collaborator: (none)
• Enrollment: 137
• Locations: 83
• Arms: 3
• Duration (Months): 25
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study has been designed as a randomized, double-blind, controlled, study to evaluate the efficacy and safety of two once daily intravenous peramivir regimens (200 mg and 400 mg) versus oral oseltamivir phosphate (75 mg twice daily) in hospitalized subjects with acute serious or potentially life threatening influenza. Study treatments will be provided for up to 5 consecutive days.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Peramivir 200 mg; Drug: Peramivir 400 mg; Drug: Oseltamivir	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II, Multicenter, Randomized, Double-Mask, Double-Dummy Study Comparing Efficacy and Safety of Intravenous Peramivir Once Daily Versus Oral Oseltamivir Twice Daily in Adults With Acute Serious or Potentially Life-Threatening Influenza
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Peramivir 200 mg Peramivir 200 mg administered intravenously once daily for 5 days (5 doses)	Drug: Peramivir 200 mg; Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment
Experimental: Arm 2: Peramivir 400 mg Peramivir 400 mg administered intravenously once daily for 5 days (5 doses)	Drug: Peramivir 400 mg; Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 ml)
Experimental: Arm 3: Oseltamivir Oseltamivir 75 mg oral suspension administered orally twice daily for 5 days (10 doses)	Drug: Oseltamivir; Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)

Outcome Measures

Primary Outcome Measures

1. Time to Clinical Stability (Kaplan-Meier Estimate) [14 days]

   Time to clinical stability was summarized overall and for individual clinical signs for each treatment group using the method of Kaplan Meier. Subjects who did not experience clinical stability were censored at the date of their last non-missing assessment during the study (whether this assessment occurred as an inpatient or as an outpatient).

Secondary Outcome Measures

1. Change From Baseline in Scores of Symptoms of Influenza [Baseline, Days 2, 3, 4, 5, 10, and 14]

   Descriptive statistics for the change from baseline in each of the 7 symptoms of influenza (cough; sore throat; nasal congestion; myalgia [aches and pains]; headache; feverishness; and fatigue, each graded on a 4-point severity scale [0, absent; 1, mild; 2, moderate; 3, severe]) were tabulated by treatment group. Missing data were excluded.

2. Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate) [14 days]

   Changes in each subject's ability to perform usual activities as determined from the visual analog scale (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) were summarized by study visit and treatment group. The time to resumption of a subject's ability to perform usual activities was estimated using the method of Kaplan Meier. Subjects who did not return to the pre-study level of performance of usual activities were censored at the time of their last assessment. (Note: N is the number of ITTI participants with available data).

3. Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study) [14 days]

   The number of subjects with clinical relapse, defined as changes in 2 or more signs of clinical stability to values outside the range of normalization criteria for a duration of at least 12 consecutive hours after clinical stability had been attained, were summarized by treatment group.

4. Time to Hospital Discharge (Kaplan-Meier Estimate) [14 days]

   Time to discharge from hospital was estimated using the method of Kaplan Meier. Subjects who were not discharged from the hospital were censored at the time of their last assessment.

5. Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined) [Baseline, and 12, 24, 36, 48, 72, and 96 hours]

   Reduction in viral shedding, assessed as the change in quantitative viral titers and defined as the time-weighted change from baseline in TCID50/mL, was summarized for each treatment group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18 years of age, male or female

• Able to provide informed consent, or for whom consent may be provided by guardian

• Presence of fever at time of screening of ≥38.0°C (≥ 100.0°F) taken orally, or ≥38.5°C (≥101.2°F) taken rectally. This requirement is waived if the subject has (1) a history of fever within 24 hours prior to screening and administered any antipyretic(s) in the 24 hours prior to screening, or (2) has no history of documented fever as defined above, but reports a symptom of feverishness at some time during 48 hours prior to screening

• Presence of at least 1 respiratory symptom (cough, sore throat, nasal congestion/symptoms) of any severity (mild, moderate, severe)

• Presence of at least 1 constitutional symptom (headache, myalgia, feverishness, malaise, fatigue) of any severity (mild, moderate, severe)

• Onset of illness no more than 72 hours before presentation. Time of onset of illness defined as either (1) the time when temperature (oral or rectal) was elevated (at least 1°C of elevation-oral temperature), OR (2) the time when the subject experienced the presence of at least 1 respiratory symptom AND the presence of at least 1 constitutional symptom

• Presence of 1 or more of the following factors in a subject willing to be hospitalized for inpatient observation and treatment:

• Age ≥60 years

• Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy

• History of congestive heart failure with or without medically significant recent change in cardiac status, but without signs or symptoms compatible with NYHA Class IV functional status

• Presence of diabetes mellitus, clinically stable or unstable

• Transcutaneous oxygen saturation <94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value

• Systolic blood pressure <90 mmHg

• Severity of illness that, in the Investigator's judgment, justifies hospitalization of the subject for supportive care

• Positive rapid antigen test (RAT) for influenza A and/or influenza B (using an approved test kit) or other test for influenza virus antigen performed in a clinical laboratory at the screening/enrollment evaluation

• Females of childbearing potential must report one of the following:

• Be surgically sterile or clinically post-menopausal

• Have been sexually abstinent 4 weeks prior to date of screening evaluation and be willing to remain abstinent through 4 weeks after study-drug administration for all perimenopausal women or women of child-bearing potential

• Use oral contraceptives or other form of hormonal birth control including hormonal vaginal rings or transdermal patches and have been using these for 3 months prior through 4 weeks after study-drug administration for all perimenopausal women or women of child-bearing potential

• Use an intra-uterine device (IUD), or adequate barrier contraception (or double-barrier method such as condom or diaphragm with spermicidal gel or foam) as birth control 4 weeks prior to date of screening evaluation through 4 weeks after study drug administration for all perimenopausal women or women of child-bearing potential

Exclusion Criteria:

• Immunized against influenza with live attenuated virus vaccine in the previous weeks

• Treatment with any dose(s) of rimantadine, amantadine, zanamivir, or oseltamivir in the previous 7 days

• Current clinical evidence of a recognized or suspected acute non-influenzal infectious illness with onset prior to Screening

• Serum creatinine laboratory result at Screening >1.6 mg/dL or a result >25% above the upper limit of normal for the laboratory performing the test

• History of clinically significant proteinuria (≥1000 mg/24 hrs)

• History of moderate or severe renal impairment and/or previous clinical laboratory data indicating an estimated creatinine clearance <50 mL/min during the previous 12 months

• Electrocardiogram (ECG) at Screening visit showing evidence of acute ischemia, or presence of a medically significant dysrhythmia

• Presence of cardiac signs or symptoms compatible with NYHA Class III or Class IV functional status for congestive heart failure or angina (see NYHA Appendix V)

• Presence of diagnosed COPD or other chronic lung condition requiring either continuous or intermittent oxygen therapy as an outpatient. Note: Subjects who are determined to require acute supplemental oxygen therapy at the time of Screening and/or at hospital admission may be enrolled, if exclusion criteria #13 or #14 are not applicable.

• History of organ transplantation during the previous 12 months

• Known HIV infection with most recent CD4+ T-cell count ≤350 cells/mL

• History of diagnosis of any type of cancer (hematologic or solid tumor), that has required chemotherapy or radiation therapy in the previous 12 months, excluding non-melanomatous localized skin cancer

• Presence of ongoing requirement for chronic mechanical ventilation, either via oral or nasotracheal intubation or via tracheostomy, or chronic or intermittent requirement for BiPAP (bilevel positive airway pressure) at screening. Note: Subjects who require intermittent CPAP treatment for sleep apnea (without oxygen supplementation) may be enrolled

• Subjects who require acute mechanical ventilatory support of any type at the time of screening.

• History of alcohol abuse or drug addiction during the previous 12 months

• Participation in a clinical study of an experimental medication or other treatment during the previous 4 weeks

• Previous treatment with intravenous or intramuscular peramivir

• Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding

• Subjects who have been hospitalized due to a condition other than acute influenza and in whom influenza is diagnosed during hospitalization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pulmonary Associates of Mobile, P.C.	Mobile	Alabama	United States	36608
2	St. Bernards Research Center/Clopton Clinic	Jonesboro	Arkansas	United States	72401
3	Pulmonary Consultants & Primary Care Physicians Medical Group, Inc.	Orange	California	United States	92868
4	University of California Irvine Medical Center	Orange	California	United States	92868
5	University of California Davis Medical Center, Department of Emergency Medicine	Sacramento	California	United States	95817
6	Good Samaritan Hospital	San Jose	California	United States	95124
7	National Jewish Medical and Research Center, Clinical Research Unit	Denver	Colorado	United States	80206
8	Orlando Regional Healthcare	Orlando	Florida	United States	32806
9	James A. Haley Veterans Hospital, Department of Infectious Disease	Tampa	Florida	United States	33612
10	Medical College of Georgia	Augusta	Georgia	United States	30912
11	Infectious Disease Specialists of Atlanta, P.C.	Decatur	Georgia	United States	30033
12	St. Joseph's/Candler Health System, Inc.	Savannah	Georgia	United States	31405
13	Idaho Falls Infectious Diseases, PLLC	Idaho Falls	Idaho	United States	83404
14	Northwestern University	Chicago	Illinois	United States	60611
15	Springfield Clinic, LLP	Springfield	Illinois	United States	62701
16	Wishard Hospital/Indiana University	Indianapolis	Indiana	United States	46202
17	Infectious Disease of Indiana, PSC	Indianapolis	Indiana	United States	46280
18	Natchitoches Internal Medicine	Natchitoches	Louisiana	United States	71457
19	Louisiana State University Health Sciences Center-Shreveport	Shreveport	Louisiana	United States	71103
20	VA Maryland Health Care System	Baltimore	Maryland	United States	21201
21	Franklin Square Hospital	Baltimore	Maryland	United States	21237
22	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
23	Wayne State University School of Medicine	Detroit	Michigan	United States	48201
24	Henry Ford Health System	Detroit	Michigan	United States	48202
25	William Beaumont Hospital Troy	Troy	Michigan	United States	48085
26	Washington University School of Medicine	St. Louis	Missouri	United States	63110
27	Mercury Street Medical Group, PLLC	Butte	Montana	United States	59701
28	Hackensack University Medical Center, Department of Infectious Disease	Hackensack	New Jersey	United States	07601
29	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07754
30	University of New Mexico	Albuquerque	New Mexico	United States	87131-0001
31	Rochester General Hospital/University of Rochester	Rochester	New York	United States	14621-3001
32	University of Rochester Medical Center	Rochester	New York	United States	14642
33	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106-5083
34	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
35	Lowcountry Infectious Diseases, P.A.	Charleston	South Carolina	United States	29414
36	Baylor College of Medicine	Houston	Texas	United States	77030
37	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
38	Veterans Affairs Medical Center	Salem	Virginia	United States	24153
39	Franciscan Health System	Tacoma	Washington	United States	98405
40	Marshfield Clinic	Marshfield	Wisconsin	United States	54449-5703
41	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226-3522
42	Prince Of Wales Hospital	Randwick	New South Wales	Australia	2031
43	Westmead Hospital	Wentworthville	New South Wales	Australia	2145
44	Cairns Base Hospital	Cairns	Queensland	Australia	4870
45	Mater Adult Hospital	South Brisbane	Queensland	Australia	4101
46	Gold Coast Hospital	Southport	Queensland	Australia	4215
47	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
48	Repatriation General Hospital	Daw Park	South Australia	Australia	5041
49	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
50	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6060
51	Kelowna General Hospital	Kelowna	British Columbia	Canada	V1Y 3T1
52	Hamilton Health Sciences-McMaster University Medical Centre	Hamilton	Ontario	Canada	L8N 3Z5
53	St. Joseph's Healthcare Hamilton-L424	Hamilton	Ontario	Canada	L8N 4A6
54	The Ottawa Hospital - General Campus	Ottawa	Ontario	Canada	K1H 8L6
55	Mount Sinai Hospital / Toronto Medical Laboratories	Toronto	Ontario	Canada	M5G 1X5
56	Center de Sante et des Services Sociaux de Chicoutimi	Chicoutimi	Quebec	Canada	G7H 5H6
57	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4
58	Centre de sante et de services sociaux Rimouski-Neigette (CSSSRN)	Rimouski	Quebec	Canada	G5L 5T1
59	Division of Infectious Diseases	Saskatoon	Saskatchewan	Canada	S7N 0W8
60	Centre Hospitalier Universitaire de Quebec-Pavillon CHUL	Quebec		Canada	G1V 4G2
61	Princess Margaret Hospital	Hong Kong		Hong Kong
62	Queen Mary Hospital	Hong Kong		Hong Kong
63	United Christian Hospital	Hong Kong		Hong Kong
64	The Prince of Wales Hospital	Shatin - New Territories		Hong Kong
65	Christchurch Hospital	Christchurch		New Zealand
66	Waikato Hospital	Hamilton		New Zealand
67	Tauranga Hospital	Tauranga		New Zealand	3110
68	National University Hospital	Singapore		Singapore	169608
69	Tan Tock Seng Hospital	Singapore		Singapore	308433
70	Global Clinical Trial Center	Port Elizabeth	E. Cape	South Africa	6020
71	Genclin Corporation	Bloemfontein	Free State	South Africa	9301
72	Benmed / Pentagon Hospital	Benoni	Gauteng	South Africa	1500
73	Private Practice	Cape Town	Gauteng	South Africa	1724
74	Newgate Centre	Johannesburg,	Gauteng	South Africa	2001
75	DJW Navorsing	Krugersdorp	Gauteng	South Africa	1739
76	Medforum Hospital	Pretoria	Gauteng	South Africa	0001
77	Eugene Marais Hospital	Pretoria	Gauteng	South Africa	0084
78	Global Clinical Trials (GCT)	Pretoria	Gauteng	South Africa	0186
79	Dr Bhorat	Soweto	Gauteng	South Africa	1818
80	Sebastian, P	Durban	KZ-Natal	South Africa	4001
81	Eksteen, MC	Nelspruit	Mpumalanga	South Africa	1201
82	Dr. L.J. van Zyl	Worcester	W Cape	South Africa	6850
83	N1 City Hospital	Cape town	WC	South Africa	7460

Sponsors and Collaborators

• BioCryst Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00453999
• Other Study ID Numbers: BCX1812-201
• First Posted: Mar 29, 2007
• Last Update Posted: Feb 12, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by BioCryst Pharmaceuticals: influenza; flu
• Additional relevant MeSH terms: Influenza, Human; Oseltamivir; Peramivir

Study Results

Participant Flow

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Period Title: Overall Study
STARTED	45	46	46
COMPLETED	40	41	43
NOT COMPLETED	5	5	3

Baseline Characteristics

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir	Total
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)	Total of all reporting groups
Overall Participants	45	46	46	137
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.9 (24.0)	58.5 (20.9)	62.0 (21.3)	59.2 (22.0)
Sex: Female, Male (Count of Participants)
Female	25 55.6%	26 56.5%	25 54.3%	76 55.5%
Male	20 44.4%	20 43.5%	21 45.7%	61 44.5%
Race/Ethnicity, Customized (participants) [Number]
White or Caucasian	23 51.1%	21 45.7%	20 43.5%	64 46.7%
Black or African American	8 17.8%	14 30.4%	12 26.1%	34 24.8%
Asian	13 28.9%	10 21.7%	13 28.3%	36 26.3%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 2.2%	0 0%	0 0%	1 0.7%
Other	0 0%	1 2.2%	1 2.2%	2 1.5%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	163.0 (9.9)	161.6 (11.8)	168.4 (11.8)	164.4 (11.5)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	64.9 (19.8)	72.4 (22.9)	79.5 (22.7)	72.4 (22.5)
Duration of Illness at Randomization (participants) [Number]
< 48 hours	31 68.9%	32 69.6%	31 67.4%	94 68.6%
>= 48 hours to <=72 hours	14 31.1%	14 30.4%	15 32.6%	43 31.4%
Initial Composite Symptom Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	12.7 (5.19)	12.2 (5.95)	12.3 (5.46)	12.4 (5.51)
Current Smoking Status (participants) [Number]
Smoker	8 17.8%	5 10.9%	4 8.7%	17 12.4%
Nonsmoker	36 80%	40 87%	42 91.3%	118 86.1%
Missing	1 2.2%	1 2.2%	0 0%	2 1.5%
Influenza Infection (participants) [Number]
Confirmed Influenza A	26 57.8%	34 73.9%	30 65.2%	90 65.7%
Confirmed Influenza B	15 33.3%	6 13%	11 23.9%	32 23.4%
Not confirmed	4 8.9%	6 13%	5 10.9%	15 10.9%
Transcutaneous Oxygen Saturation at Randomization (participants) [Number]
< 94%	14 31.1%	14 30.4%	14 30.4%	42 30.7%
>= 94%	31 68.9%	32 69.6%	32 69.6%	95 69.3%

Outcome Measures

1. Primary Outcome

Title	Time to Clinical Stability (Kaplan-Meier Estimate)
Description	Time to clinical stability was summarized overall and for individual clinical signs for each treatment group using the method of Kaplan Meier. Subjects who did not experience clinical stability were censored at the date of their last non-missing assessment during the study (whether this assessment occurred as an inpatient or as an outpatient).
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The intent-to-treat infected (ITTI) population included all subjects who were randomized, received at least 1 dose of study drug, and had confirmed influenza infection by viral culture, PCR, and/or paired acute and convalescent serology specimens that demonstrated at least a 4-fold increase in antibody titer against influenza A or B.

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution ) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Measure Participants	41	40	41
Median (95% Confidence Interval) [hours]	23.7	37.0	28.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.306
	Comments
	Method	Log Rank
	Comments	Differences between groups by log-rank statistic stratified by oxygen saturation and duration of illness at randomization, and flu season.

2. Secondary Outcome

Title	Change From Baseline in Scores of Symptoms of Influenza
Description	Descriptive statistics for the change from baseline in each of the 7 symptoms of influenza (cough; sore throat; nasal congestion; myalgia [aches and pains]; headache; feverishness; and fatigue, each graded on a 4-point severity scale [0, absent; 1, mild; 2, moderate; 3, severe]) were tabulated by treatment group. Missing data were excluded.
Time Frame	Baseline, Days 2, 3, 4, 5, 10, and 14

Outcome Measure Data

Analysis Population Description

The intent-to-treat infected (ITTI) population included all subjects who were randomized, received at least 1 dose of study drug, and had confirmed influenza infection by viral culture, PCR, and/or paired acute and convalescent serology specimens that demonstrated at least a 4-fold increase in antibody titer against influenza A or B.

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Measure Participants	41	40	41
Sore Throat: Baseline	1.3 (1.09)	1.1 (1.17)	1.2 (1.19)
Sore Throat: Change at Day 2	-0.2 (0.95)	-0.3 (1.09)	-0.3 (0.80)
Sore Throat: Change at Day 3	-0.8 (1.05)	-0.7 (1.24)	-0.8 (1.04)
Sore Throat: Change at Day 4	-0.9 (1.13)	-0.9 (1.24)	-1.1 (1.18)
Sore Throat: Change at Day 5	-1.1 (1.07)	-0.9 (1.20)	-1.1 (1.24)
Sore Throat: Change at Day 10	-1.2 (1.03)	-1.1 (1.15)	-1.2 (1.18)
Sore Throat: Change at Day 14	-1.2 (1.05)	-1.1 (1.16)	-1.1 (1.17)
Nasal Congestion: Baseline	1.3 (1.17)	1.5 (1.03)	1.3 (1.08)
Nasal Congestion: Change at Day 2	-0.2 (1.06)	-0.5 (0.82)	-0.3 (0.82)
Nasal Congestion: Change at Day 3	-0.7 (1.18)	-0.9 (0.99)	-0.8 (0.96)
Nasal Congestion: Change at Day 4	-0.8 (1.32)	-1.1 (1.06)	-1.0 (1.16)
Nasal Congestion: Change at Day 5	-0.9 (1.27)	-1.2 (1.17)	-1.1 (1.10)
Nasal Congestion: Change at Day 10	-1.1 (1.23)	-1.2 (1.27)	-1.1 (1.17)
Nasal Congestion: Change at Day 14	-1.0 (1.22)	-1.2 (1.17)	-1.3 (1.08)
Cough: Baseline	2.2 (0.73)	2.0 (0.77)	2.1 (0.76)
Cough: Change at Day 2	-0.4 (0.88)	-0.3 (0.74)	-0.2 (0.81)
Cough: Change at Day 3	-0.9 (0.91)	-0.9 (1.07)	-0.9 (0.87)
Cough: Change at Day 4	-1.1 (1.10)	-1.1 (1.05)	-1.0 (1.07)
Cough: Change at Day 5	-1.2 (0.97)	-1.1 (1.23)	-1.1 (1.17)
Cough: Change at Day 10	-1.4 (0.97)	-1.2 (1.07)	-1.3 (1.11)
Cough: Change at Day 14	-1.6 (1.06)	-1.4 (1.01)	-1.5 (1.09)
Aches and Pains: Baseline	1.8 (1.30)	1.9 (1.13)	1.9 (1.09)
Aches and Pains: Change at Day 2	-0.8 (1.01)	-0.8 (0.91)	-0.8 (1.08)
Aches and Pains: Change at Day 3	-1.3 (1.14)	-1.4 (1.18)	-1.4 (1.14)
Aches and Pains: Change at Day 4	-1.5 (1.28)	-1.6 (1.21)	-1.6 (1.21)
Aches and Pains: Change at Day 5	-1.6 (1.31)	-1.6 (1.23)	-1.7 (1.31)
Aches and Pains: Change at Day 10	-1.7 (1.38)	-1.7 (1.12)	-1.9 (1.09)
Aches and Pains: Change at Day 14	-1.7 (1.35)	-1.6 (1.11)	-1.7 (1.30)
Fatigue: Baseline	2.3 (0.78)	2.0 (0.96)	2.3 (0.82)
Fatigue: Change at Day 2	-0.9 (0.96)	-0.5 (1.12)	-1.0 (1.11)
Fatigue: Change at Day 3	-1.2 (1.02)	-1.0 (1.26)	-1.1 (1.17)
Fatigue: Change at Day 4	-1.4 (1.21)	-1.2 (1.30)	-1.6 (1.11)
Fatigue: Change at Day 5	-1.6 (1.09)	-1.3 (1.27)	-1.7 (1.09)
Fatigue: Change at Day 10	-1.7 (1.05)	-1.4 (1.13)	-1.7 (1.09)
Fatigue: Change at Day 14	-1.7 (1.13)	-1.6 (1.01)	-2.0 (0.97)
Headache: Baseline	1.5 (1.22)	1.3 (1.34)	1.4 (1.30)
Headache: Change at Day 2	-0.5 (1.11)	-0.5 (1.12)	-0.6 (0.94)
Headache: Change at Day 3	-0.9 (1.16)	-1.0 (1.26)	-1.0 (1.10)
Headache: Change at Day 4	-1.0 (1.25)	-1.1 (1.30)	-1.1 (1.30)
Headache: Change at Day 5	-1.2 (1.21)	-1.1 (1.28)	-1.3 (1.30)
Headache: Change at Day 10	-1.3 (1.24)	-1.2 (1.35)	-1.4 (1.26)
Headache: Change at Day 14	-1.3 (1.19)	-1.2 (1.35)	-1.3 (1.34)
Feeling Feverish: Baseline	2.1 (1.04)	1.9 (0.99)	1.8 (1.20)
Feeling Feverish: Change at Day 2	-1.4 (1.02)	-1.0 (0.94)	-1.0 (1.15)
Feeling Feverish: Change at Day 3	-1.5 (1.01)	-1.5 (0.93)	-1.6 (1.20)
Feeling Feverish: Change at Day 4	-1.8 (1.15)	-1.8 (0.97)	-1.6 (1.48)
Feeling Feverish: Change at Day 5	-1.9 (1.02)	-1.8 (1.02)	-1.8 (1.20)
Feeling Feverish: Change at Day 10	-2.0 (1.07)	-1.8 (1.00)	-1.8 (1.18)
Feeling Feverish: Change at Day 14	-1.9 (1.21)	-1.7 (1.01)	-1.8 (1.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Sore Throat: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Nasal Congestion: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Cough: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Aches and Pains: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Fatigue: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Headache: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Feeling Feverish: change from Baseline at Days 2, 3, 4, 5, 10, 14
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

3. Secondary Outcome

Title	Time to Resumption of Ability to Perform Usual Activities (Kaplan-Meier Estimate)
Description	Changes in each subject's ability to perform usual activities as determined from the visual analog scale (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) were summarized by study visit and treatment group. The time to resumption of a subject's ability to perform usual activities was estimated using the method of Kaplan Meier. Subjects who did not return to the pre-study level of performance of usual activities were censored at the time of their last assessment. (Note: N is the number of ITTI participants with available data).
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The intent-to-treat infected (ITTI) population included all subjects who were randomized, received at least 1 dose of study drug, and had confirmed influenza infection by viral culture, PCR, and/or paired acute and convalescent serology specimens that demonstrated at least a 4-fold increase in antibody titer against influenza A or B.

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Measure Participants	40	39	41
Median (95% Confidence Interval) [hours]	8.8	9.0	13.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.276
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Incidence of Clinical Relapse of Influenza After Treatment (Number of Participants Experiencing Relapse During the Study)
Description	The number of subjects with clinical relapse, defined as changes in 2 or more signs of clinical stability to values outside the range of normalization criteria for a duration of at least 12 consecutive hours after clinical stability had been attained, were summarized by treatment group.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The intent-to-treat infected (ITTI) population included all subjects who were randomized, received at least 1 dose of study drug, and had confirmed influenza infection by viral culture, PCR, and/or paired acute and convalescent serology specimens that demonstrated at least a 4-fold increase in antibody titer against influenza A or B.

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Measure Participants	41	40	41
Number [participants]	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Time to Hospital Discharge (Kaplan-Meier Estimate)
Description	Time to discharge from hospital was estimated using the method of Kaplan Meier. Subjects who were not discharged from the hospital were censored at the time of their last assessment.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The intent-to-treat infected (ITTI) population included all subjects who were randomized, received at least 1 dose of study drug, and had confirmed influenza infection by viral culture, PCR, and/or paired acute and convalescent serology specimens that demonstrated at least a 4-fold increase in antibody titer against influenza A or B.

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Measure Participants	41	40	41
Median (95% Confidence Interval) [hours]	4.0	3.8	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.994
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Change in Amount of Influenza Virus in Nose and Throat (Influenza A and B Combined)
Description	Reduction in viral shedding, assessed as the change in quantitative viral titers and defined as the time-weighted change from baseline in TCID50/mL, was summarized for each treatment group.
Time Frame	Baseline, and 12, 24, 36, 48, 72, and 96 hours

Outcome Measure Data

Analysis Population Description

Among the 122 subjects with confirmed influenza (intent-to-treat infected [ITTI]) population, a total of 112 subjects had positive virus cultures obtained from baseline nasopharyngeal specimens.

Arm/Group Title	Peramivir 200 mg	Peramivir 400 mg	Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment	Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)	Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
Measure Participants	39	34	39
Duration <48 Hours: Baseline	3.6 (1.33)	3.5 (1.01)	3.4 (1.44)
Duration <48 Hours: Change at 12 hours	-1.5 (1.33)	-1.6 (1.29)	-1.5 (1.01)
Duration <48 Hours: Change at 24 hours	-2.5 (0.93)	-2.2 (0.84)	-2.2 (0.99)
Duration <48 Hours: Change at 48 hours	-2.4 (0.93)	-2.9 (0.77)	-2.5 (1.45)
Duration <48 Hours: Change at 96 hours	-2.8 (1.28)	-3.0 (0.97)	-2.8 (1.05)
Duration ≥48 and ≤72 hours: Baseline	2.8 (1.38)	2.6 (1.35)	2.5 (1.27)
Duration ≥48 and ≤72 hours: Change at 12 hours	-1.1 (1.03)	-1.5 (1.27)	-0.7 (1.12)
Duration ≥48 and ≤72 hours: Change at 24 hours	-1.4 (0.92)	-1.7 (1.22)	-1.0 (0.75)
Duration ≥48 and ≤72 hours: Change at 48 hours	-1.8 (1.17)	-1.9 (1.16)	-1.5 (0.85)
Duration ≥48 and ≤72 hours: Change at 96 hours	-2.6 (1.29)	-2.0 (1.38)	-1.7 (1.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Change from Baseline at 12 hours
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Change from Baseline at 24 hours
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Change from Baseline at 36 hours
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Change from Baseline at 48 hours
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Change from Baseline at 72 hours
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Peramivir 200 mg, Peramivir 400 mg, Oseltamivir
	Comments	Change from Baseline at 96 hours
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Adverse Events

Time Frame	Adverse events were collected from the time of study drug administration through the follow-up period ending on Day 14.
Adverse Event Reporting Description	For subjects who experienced the same coded event more than once, only one event is presented.
Arm/Group Title	Peramivir 200 mg		Peramivir 400 mg		Oseltamivir
Arm/Group Description	Peramivir (200 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL) treatment		Peramivir (400 mg in 100 mL of solution) intravenous infusion (over 15 minutes) and an orally administered oseltamivir placebo suspension (6.25 mL)		Placebo peramivir infusion (over 15 minutes) and a 75-mg dose of oseltamivir suspension (6.25 mL)
All Cause Mortality
	Peramivir 200 mg		Peramivir 400 mg		Oseltamivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Peramivir 200 mg		Peramivir 400 mg		Oseltamivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/45 (4.4%)		8/46 (17.4%)		4/46 (8.7%)
Blood and lymphatic system disorders
Anaemia	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Hypocoagulable state	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Cardiac disorders
Supraventricular tachycardia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Gastrointestinal disorders
Diarrhoea	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Gastrointestinal haemorrhage	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Infections and infestations
Pneumonia	0/45 (0%)		3/46 (6.5%)		0/46 (0%)
Respiratory tract infection	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Viral myocarditis	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Nervous system disorders
Presyncope	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Renal and urinary disorders
Proteinuria	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Urinary retention	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Chronic obstructive pulmonary disease	0/45 (0%)		1/46 (2.2%)		1/46 (2.2%)
Respiratory failure	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Skin and subcutaneous tissue disorders
Angioedema	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Peramivir 200 mg		Peramivir 400 mg		Oseltamivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/45 (55.6%)		21/46 (45.7%)		19/46 (41.3%)
Blood and lymphatic system disorders
Lymphadenopathy	1/45 (2.2%)		0/46 (0%)		1/46 (2.2%)
Neutropenia	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Anaemia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Leukopenia	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Cardiac disorders
Arrhythmia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Atrial Fibrillation	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Bradycardia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Cardiac Failure Congestive	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Cardiomegaly	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Ventricular Tachycardia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Endocrine disorders
Thyroiditis	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Eye disorders
Vision Blurred	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Gastrointestinal disorders
Diarrhoea	5/45 (11.1%)		7/46 (15.2%)		1/46 (2.2%)
Nausea	2/45 (4.4%)		5/46 (10.9%)		4/46 (8.7%)
Constipation	3/45 (6.7%)		0/46 (0%)		1/46 (2.2%)
Vomiting	1/45 (2.2%)		0/46 (0%)		1/46 (2.2%)
Abdominal Discomfort	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Abdominal Pain	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Abdominal Pain Upper	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Dry Mouth	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Dysphagia	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Epigastric Discomfort	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Gastrooesophageal Reflux Disease	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Gingival Pain	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Haemorrhoidal Haemorrhage	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
General disorders
Oedema	0/45 (0%)		0/46 (0%)		2/46 (4.3%)
Chest Pain	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Infusion Site Pain	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Infusion Site Pruritus	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Malaise	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Non-cardiac Chest Pain	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Pain	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Pyrexia	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Vessel Puncture Site Haematoma	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Immune system disorders
Hypersensitivity	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Infections and infestations
Bacterial Sepsis	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Bronchiectasis	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Candidiasis	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Fungal Skin Infection	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Oral Candidiasis	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Pneumonia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Staphylococcal Sepsis	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Urinary Tract Infection	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Injury, poisoning and procedural complications
Contusion	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Investigations
Alanine Aminotransferase Increased	1/45 (2.2%)		0/46 (0%)		1/46 (2.2%)
Aspartate Aminotransferase Increased	1/45 (2.2%)		0/46 (0%)		1/46 (2.2%)
Blood Creatine Phosphokinase Increased	0/45 (0%)		2/46 (4.3%)		0/46 (0%)
Blood Alkaline Phosphatase Decreased	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Blood Lactate Dehydrogenase Increased	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Blood Magnesium Decreased	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Blood Pressure Increased	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Brain Natriuretic Peptide Increased	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Electrocardiogram Change	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Electrocardiogram Qt Prolonged	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Hepatic Enzyme Increased	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Lymphocyte Count Decreased	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Weight Decreased	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
White Blood Cell Count Increased	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Metabolism and nutrition disorders
Hypokalaemia	3/45 (6.7%)		4/46 (8.7%)		5/46 (10.9%)
Hyperglycaemia	2/45 (4.4%)		2/46 (4.3%)		2/46 (4.3%)
Anorexia	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Hypoalbuminaemia	0/45 (0%)		1/46 (2.2%)		1/46 (2.2%)
Hypocalcaemia	0/45 (0%)		0/46 (0%)		2/46 (4.3%)
Decreased Appetite	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Hypomagnesaemia	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Hyponatraemia	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Hypoproteinaemia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Musculoskeletal and connective tissue disorders
Back Pain	1/45 (2.2%)		0/46 (0%)		1/46 (2.2%)
Muscle Spasms	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Musculoskeletal Discomfort	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Nervous system disorders
Headache	1/45 (2.2%)		2/46 (4.3%)		0/46 (0%)
Dizziness	0/45 (0%)		1/46 (2.2%)		1/46 (2.2%)
Dizziness Postural	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Paraesthesia	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Somnolence	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Tremor	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Psychiatric disorders
Insomnia	2/45 (4.4%)		2/46 (4.3%)		2/46 (4.3%)
Anxiety	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Depression	2/45 (4.4%)		0/46 (0%)		0/46 (0%)
Confusional State	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Delirium	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Mood Altered	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Nightmare	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Restlessness	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Renal and urinary disorders
Proteinuria	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/45 (2.2%)		1/46 (2.2%)		1/46 (2.2%)
Dyspnoea	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Atelectasis	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Bronchial Secretion Retention	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Epistaxis	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Haemoptysis	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Hypoxia	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Paranasal Sinus Hypersecretion	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Pharyngeal Erythema	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Pleural Effusion	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Productive Cough	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Sputum Discoloured	0/45 (0%)		1/46 (2.2%)		0/46 (0%)
Wheezing	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Skin and subcutaneous tissue disorders
Dry Skin	0/45 (0%)		1/46 (2.2%)		1/46 (2.2%)
Pruritus	0/45 (0%)		1/46 (2.2%)		1/46 (2.2%)
Rash	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Rash Maculo-papular	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Rash Papular	0/45 (0%)		0/46 (0%)		1/46 (2.2%)
Urticaria	1/45 (2.2%)		0/46 (0%)		0/46 (0%)
Vascular disorders
Hypotension	1/45 (2.2%)		1/46 (2.2%)		0/46 (0%)
Hypertension	0/45 (0%)		0/46 (0%)		1/46 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.