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Comparing the Efficacy, Safety, and Tolerability of Combination Antivirals (Amantadine, Ribavirin, Oseltamivir) Versus Oseltamivir for the Treatment of Influenza in Adults at Risk for Complications (IRC003)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01227967
Recruitment Status : Completed
First Posted : October 25, 2010
Results First Posted : July 11, 2017
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Influenza
Interventions Drug: Amantadine, Ribavirin, Oseltamivir
Drug: Oseltamivir
Enrollment 881
Recruitment Details Outpatient or hospitalized participants at high risk for complications and morbidity, diagnosed with influenza by rapid antigen or PCR were recruited at 65 sites from 5 countries: 52 from the U.S., 2 from Australia, 3 from Mexico, and 4 each in Thailand and Argentina, between March 2011 to April 2016.
Pre-assignment Details Eight hundred eighty-one subjects were enrolled per protocol (signed consent). Two hundred fifty-one subjects were excluded during screening and did not participate in any other aspect of the trial. Three subjects were randomized improperly because they were given study drug kit prior to the randomization.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Period Title: Overall Study
Started 314 316
Completed [1] 298 303
Not Completed 16 13
Reason Not Completed
Protocol Violation             3             1
Death             0             1
Lost to Follow-up             8             3
Withdrawal by Subject             4             3
Physician Decision             0             1
Never Started Treatment             0             4
Taking Additional Antiviral Drug             1             0
[1]
Results were through database cutoff (10 November 2016) for efficacy analysis (through Day 28 visit)
Arm/Group Title Combination Therapy Oseltamivir Monotherapy Total
Hide Arm/Group Description

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Total of all reporting groups
Overall Number of Baseline Participants 314 312 626
Hide Baseline Analysis Population Description
Intent To Treat (ITT) Population: all participants who were randomized properly and who had received at least one dose of study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
<=18 years
1
   0.3%
4
   1.3%
5
   0.8%
Between 18 and 65 years
252
  80.3%
241
  77.2%
493
  78.8%
>=65 years
61
  19.4%
67
  21.5%
128
  20.4%
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 314 participants 312 participants 626 participants
49.5
(37 to 61)
49.5
(35.5 to 61)
49.5
(36 to 61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
Female
187
  59.6%
198
  63.5%
385
  61.5%
Male
127
  40.4%
114
  36.5%
241
  38.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
Hispanic or Latino
55
  17.5%
58
  18.6%
113
  18.1%
Not Hispanic or Latino
258
  82.2%
254
  81.4%
512
  81.8%
Unknown or Not Reported
1
   0.3%
0
   0.0%
1
   0.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
White
203
  64.6%
189
  60.6%
392
  62.6%
Asian
70
  22.3%
73
  23.4%
143
  22.8%
Black or African American
18
   5.7%
25
   8.0%
43
   6.9%
American Indian
1
   0.3%
2
   0.6%
3
   0.5%
Race not available to clinic
21
   6.7%
21
   6.7%
42
   6.7%
Subject does not want to report
1
   0.3%
1
   0.3%
2
   0.3%
Subject does not know
0
   0.0%
1
   0.3%
1
   0.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Argentina Number Analyzed 314 participants 312 participants 626 participants
12 10 22
United States Number Analyzed 314 participants 312 participants 626 participants
220 216 436
Mexico Number Analyzed 314 participants 312 participants 626 participants
17 18 35
Australia Number Analyzed 314 participants 312 participants 626 participants
0 2 2
Thailand Number Analyzed 314 participants 312 participants 626 participants
65 66 131
Influenza Diagnostic Test by Local Testing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
RT-PCR/PCR
33
  10.5%
30
   9.6%
63
  10.1%
Rapid antigen test
281
  89.5%
281
  90.1%
562
  89.8%
Isothermal nucleic acid amplification technology
0
   0.0%
1
   0.3%
1
   0.2%
Positive Influenza Test by Local Testing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
314
 100.0%
312
 100.0%
626
 100.0%
Result of Influenza Test By Local Testing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
Influenza A/H1N1
13
   4.1%
14
   4.5%
27
   4.3%
Influenza A/H3N2
1
   0.3%
1
   0.3%
2
   0.3%
Influenza A unsubtypable
29
   9.2%
22
   7.1%
51
   8.1%
Influenza A not typed
180
  57.3%
180
  57.7%
360
  57.5%
Influenza B
75
  23.9%
80
  25.6%
155
  24.8%
Influenza positive (unknown A or B)
10
   3.2%
5
   1.6%
15
   2.4%
Multiple types/subtypes
6
   1.9%
10
   3.2%
16
   2.6%
Confirmed Influenza Infection Status By Central Testing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
Yes
230
  73.2%
224
  71.8%
454
  72.5%
No
84
  26.8%
88
  28.2%
172
  27.5%
Influenza Type/Subtype By Central Testing   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
Influenza A/H3N2
126
  40.1%
118
  37.8%
244
  39.0%
Influenza A/H1N1
55
  17.5%
49
  15.7%
104
  16.6%
Influenza B
49
  15.6%
57
  18.3%
106
  16.9%
Negative
83
  26.4%
86
  27.6%
169
  27.0%
Missing
1
   0.3%
2
   0.6%
3
   0.5%
[1]
Measure Description: Influenza type/subtype by central lab testing was from site-collected swab on Day 0 (the first one if more than one was collected) and if that was missing, then from a Day -1 sample, if collected
Quantitative PCR Viral Shedding   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 230 participants 224 participants 454 participants
6.4
(5.6 to 7.2)
6.7
(5.1 to 7.7)
6.5
(5.4 to 7.4)
[1]
Measure Description:

Limit of detection (LOD)/lower limit of quantification (LLOQ) for Flu A and Flu B by qPCR is 3.2/3.9 and 3.4/4.0, respectively.

Results <LOD were imputed as LOD; results >=LOD and <LLOQ were imputed as LLOQ, and results >ULOQ were imputed as ULOQ

[2]
Measure Analysis Population Description: The results are for the 454 participants with a confirmed positive test for influenza on a Day 0 sample from the central laboratory using a RT-PCR for influenza type and subtype.
Presence of fever  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 314 participants 312 participants 626 participants
Yes
94
  29.9%
93
  29.8%
187
  29.9%
No
216
  68.8%
216
  69.2%
432
  69.0%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Symptom Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Cough Number Analyzed 314 participants 312 participants 626 participants
Absent
18
   5.7%
14
   4.5%
32
   5.1%
Mild
68
  21.7%
86
  27.6%
154
  24.6%
Moderate
139
  44.3%
130
  41.7%
269
  43.0%
Severe
85
  27.1%
78
  25.0%
163
  26.0%
Missing
4
   1.3%
4
   1.3%
8
   1.3%
Fatigue Number Analyzed 314 participants 312 participants 626 participants
Absent
28
   8.9%
15
   4.8%
43
   6.9%
Mild
33
  10.5%
43
  13.8%
76
  12.1%
Moderate
117
  37.3%
105
  33.7%
222
  35.5%
Severe
132
  42.0%
145
  46.5%
277
  44.2%
Missing
4
   1.3%
4
   1.3%
8
   1.3%
Feverishness Number Analyzed 314 participants 312 participants 626 participants
Absent
70
  22.3%
62
  19.9%
132
  21.1%
Mild
61
  19.4%
68
  21.8%
129
  20.6%
Moderate
111
  35.4%
98
  31.4%
209
  33.4%
Severe
68
  21.7%
80
  25.6%
148
  23.6%
Missing
4
   1.3%
4
   1.3%
8
   1.3%
Diarrhea Number Analyzed 314 participants 312 participants 626 participants
Absent
231
  73.6%
253
  81.1%
484
  77.3%
Mild
36
  11.5%
26
   8.3%
62
   9.9%
Moderate
26
   8.3%
20
   6.4%
46
   7.3%
Severe
15
   4.8%
10
   3.2%
25
   4.0%
Missing
6
   1.9%
3
   1.0%
9
   1.4%
Muscle aches Number Analyzed 314 participants 312 participants 626 participants
Absent
44
  14.0%
30
   9.6%
74
  11.8%
Mild
51
  16.2%
56
  17.9%
107
  17.1%
Moderate
100
  31.8%
99
  31.7%
199
  31.8%
Severe
115
  36.6%
124
  39.7%
239
  38.2%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Vomiting Number Analyzed 314 participants 312 participants 626 participants
Absent
268
  85.4%
269
  86.2%
537
  85.8%
Mild
18
   5.7%
18
   5.8%
36
   5.8%
Moderate
16
   5.1%
12
   3.8%
28
   4.5%
Severe
6
   1.9%
9
   2.9%
15
   2.4%
Missing
6
   1.9%
4
   1.3%
10
   1.6%
Headache Number Analyzed 314 participants 312 participants 626 participants
Absent
60
  19.1%
55
  17.6%
115
  18.4%
Mild
76
  24.2%
81
  26.0%
157
  25.1%
Moderate
99
  31.5%
99
  31.7%
198
  31.6%
Severe
75
  23.9%
74
  23.7%
149
  23.8%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Nausea Number Analyzed 314 participants 312 participants 626 participants
Absent
197
  62.7%
198
  63.5%
395
  63.1%
Mild
54
  17.2%
51
  16.3%
105
  16.8%
Moderate
38
  12.1%
35
  11.2%
73
  11.7%
Severe
19
   6.1%
24
   7.7%
43
   6.9%
Missing
6
   1.9%
4
   1.3%
10
   1.6%
Sore throat Number Analyzed 314 participants 312 participants 626 participants
Absent
80
  25.5%
80
  25.6%
160
  25.6%
Mild
94
  29.9%
91
  29.2%
185
  29.6%
Moderate
102
  32.5%
91
  29.2%
193
  30.8%
Severe
34
  10.8%
47
  15.1%
81
  12.9%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Stuffy nose Number Analyzed 314 participants 312 participants 626 participants
Absent
82
  26.1%
66
  21.2%
148
  23.6%
Mild
62
  19.7%
68
  21.8%
130
  20.8%
Moderate
107
  34.1%
96
  30.8%
203
  32.4%
Severe
59
  18.8%
78
  25.0%
137
  21.9%
Missing
4
   1.3%
4
   1.3%
8
   1.3%
Rhinorrhea Number Analyzed 314 participants 312 participants 626 participants
Absent
77
  24.5%
54
  17.3%
131
  20.9%
Mild
79
  25.2%
96
  30.8%
175
  28.0%
Moderate
96
  30.6%
84
  26.9%
180
  28.8%
Severe
56
  17.8%
74
  23.7%
130
  20.8%
Missing
6
   1.9%
4
   1.3%
10
   1.6%
[1]
Measure Description: Symptoms were scored on a 4-point scale : 0=absent, 1=mild, 2=moderate, 3=severe
Overall Symptom Score   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 314 participants 312 participants 626 participants
15
(11 to 19)
15
(11 to 19)
15
(11 to 19)
[1]
Measure Description: Overall symptom score was the sum of available scores for each of the 11 symptoms assessed (so ignoring missing values). The possible range of the overall symptom score is therefore 0 (no symptoms) to 44 (severe for all 10 symptoms). Participants with missing evaluations for all symptoms were given a missing overall symptom score.
Functional status  
Measure Type: Count of Participants
Unit of measure:  Participants
Vigorous activities Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
238
  75.8%
238
  76.3%
476
  76.0%
Limited a little = 50
58
  18.5%
59
  18.9%
117
  18.7%
Not limited at all = 100
14
   4.5%
12
   3.8%
26
   4.2%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Moderate activities Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
167
  53.2%
171
  54.8%
338
  54.0%
Limited a little = 50
114
  36.3%
107
  34.3%
221
  35.3%
Not limited at all = 100
29
   9.2%
31
   9.9%
60
   9.6%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Lifting groceries Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
99
  31.5%
116
  37.2%
215
  34.3%
Limited a little = 50
129
  41.1%
114
  36.5%
243
  38.8%
Not limited at all = 100
82
  26.1%
79
  25.3%
161
  25.7%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Climbing stairs Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
182
  58.0%
172
  55.1%
354
  56.5%
Limited a little = 50
97
  30.9%
105
  33.7%
202
  32.3%
Not limited at all = 100
31
   9.9%
32
  10.3%
63
  10.1%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Climbing 1 flight Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
97
  30.9%
103
  33.0%
200
  31.9%
Limited a little = 50
146
  46.5%
129
  41.3%
275
  43.9%
Not limited at all = 100
67
  21.3%
77
  24.7%
144
  23.0%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Bending or kneeling Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
89
  28.3%
82
  26.3%
171
  27.3%
Limited a little = 50
118
  37.6%
133
  42.6%
251
  40.1%
Not limited at all = 100
103
  32.8%
94
  30.1%
197
  31.5%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Walking > 1 mile Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
199
  63.4%
202
  64.7%
401
  64.1%
Limited a little = 50
81
  25.8%
78
  25.0%
159
  25.4%
Not limited at all = 100
30
   9.6%
29
   9.3%
59
   9.4%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Walking blocks Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
169
  53.8%
177
  56.7%
346
  55.3%
Limited a little = 50
100
  31.8%
91
  29.2%
191
  30.5%
Not limited at all = 100
41
  13.1%
41
  13.1%
82
  13.1%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Walking a block Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
101
  32.2%
108
  34.6%
209
  33.4%
Limited a little = 50
123
  39.2%
111
  35.6%
234
  37.4%
Not limited at all = 100
86
  27.4%
90
  28.8%
176
  28.1%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Bathing/dressing self Number Analyzed 314 participants 312 participants 626 participants
Limited a lot = 0
48
  15.3%
54
  17.3%
102
  16.3%
Limited a little = 50
72
  22.9%
83
  26.6%
155
  24.8%
Not limited at all = 100
190
  60.5%
172
  55.1%
362
  57.8%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Average Functional Status   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 314 participants 312 participants 626 participants
35
(20 to 60)
35
(15 to 55)
35
(15 to 60)
[1]
Measure Description: Average functional status was calculated as the average of the ten items assessed (so ignoring missing values), scoring 0='yes, limited a lot', 50='yes, limited a little', 100='no, not limited at all'. The possible range of the functional status score is therefore 0 (worst possible status) to 100 (best possible status). Participants with missing evaluations for all items were given a missing average functional status.
Global assessment  
Measure Type: Count of Participants
Unit of measure:  Participants
Subject feels as good today as before flu Number Analyzed 314 participants 312 participants 626 participants
Yes
9
   2.9%
7
   2.2%
16
   2.6%
No
301
  95.9%
302
  96.8%
603
  96.3%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Subject functions as well today as before flu Number Analyzed 314 participants 312 participants 626 participants
Yes
23
   7.3%
20
   6.4%
43
   6.9%
No
287
  91.4%
289
  92.6%
576
  92.0%
Missing
4
   1.3%
3
   1.0%
7
   1.1%
Complications of Influenza  
Measure Type: Count of Participants
Unit of measure:  Participants
Sinusitis Number Analyzed 314 participants 312 participants 626 participants
Yes
11
   3.5%
14
   4.5%
25
   4.0%
No
298
  94.9%
298
  95.5%
596
  95.2%
Unable to assess
2
   0.6%
0
   0.0%
2
   0.3%
Missing
3
   1.0%
0
   0.0%
3
   0.5%
Otitis Media Number Analyzed 314 participants 312 participants 626 participants
Yes
2
   0.6%
4
   1.3%
6
   1.0%
No
307
  97.8%
308
  98.7%
615
  98.2%
Unable to assess
2
   0.6%
0
   0.0%
2
   0.3%
Missing
3
   1.0%
0
   0.0%
3
   0.5%
Bronchitis/Bronchiolitis Number Analyzed 314 participants 312 participants 626 participants
Yes
8
   2.5%
14
   4.5%
22
   3.5%
No
301
  95.9%
298
  95.5%
599
  95.7%
Unable to assess
2
   0.6%
0
   0.0%
2
   0.3%
Missing
3
   1.0%
0
   0.0%
3
   0.5%
Pneumonia Number Analyzed 314 participants 312 participants 626 participants
Yes
5
   1.6%
9
   2.9%
14
   2.2%
No
304
  96.8%
303
  97.1%
607
  97.0%
Unable to assess
2
   0.6%
0
   0.0%
2
   0.3%
Missing
3
   1.0%
0
   0.0%
3
   0.5%
Using antibiotic for other reasons Number Analyzed 314 participants 312 participants 626 participants
Yes
20
   6.4%
21
   6.7%
41
   6.5%
No
291
  92.7%
291
  93.3%
582
  93.0%
Unable to assess
0
   0.0%
0
   0.0%
0
   0.0%
Missing
3
   1.0%
0
   0.0%
3
   0.5%
Medical Conditions   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
>= 65 years Number Analyzed 314 participants 312 participants 626 participants
Yes
251
  79.9%
247
  79.2%
498
  79.6%
No
63
  20.1%
65
  20.8%
128
  20.4%
Asthma Number Analyzed 314 participants 312 participants 626 participants
Yes
214
  68.2%
213
  68.3%
427
  68.2%
No
100
  31.8%
99
  31.7%
199
  31.8%
Neurological condition Number Analyzed 314 participants 312 participants 626 participants
Yes
297
  94.6%
293
  93.9%
590
  94.2%
No
17
   5.4%
19
   6.1%
36
   5.8%
Chronic Lung disease Number Analyzed 314 participants 312 participants 626 participants
Yes
297
  94.6%
291
  93.3%
588
  93.9%
No
17
   5.4%
21
   6.7%
38
   6.1%
Heart disease Number Analyzed 314 participants 312 participants 626 participants
Yes
284
  90.4%
273
  87.5%
557
  89.0%
No
30
   9.6%
39
  12.5%
69
  11.0%
Blood disorder Number Analyzed 314 participants 312 participants 626 participants
Yes
306
  97.5%
307
  98.4%
613
  97.9%
No
8
   2.5%
5
   1.6%
13
   2.1%
Endocrine Number Analyzed 314 participants 312 participants 626 participants
Yes
227
  72.3%
224
  71.8%
451
  72.0%
No
87
  27.7%
88
  28.2%
175
  28.0%
Kidney Number Analyzed 314 participants 312 participants 626 participants
Yes
306
  97.5%
306
  98.1%
612
  97.8%
No
8
   2.5%
6
   1.9%
14
   2.2%
Liver disorder Number Analyzed 314 participants 312 participants 626 participants
Yes
311
  99.0%
305
  97.8%
616
  98.4%
No
3
   1.0%
7
   2.2%
10
   1.6%
Metabolic Number Analyzed 314 participants 312 participants 626 participants
Yes
302
  96.2%
304
  97.4%
606
  96.8%
No
12
   3.8%
8
   2.6%
20
   3.2%
Weakened immune system Number Analyzed 314 participants 312 participants 626 participants
Yes
270
  86.0%
266
  85.3%
536
  85.6%
No
44
  14.0%
46
  14.7%
90
  14.4%
BMI >= 40 Number Analyzed 314 participants 312 participants 626 participants
Yes
240
  76.4%
261
  83.7%
501
  80.0%
No
74
  23.6%
51
  16.3%
125
  20.0%
[1]
Measure Description: Medication conditions that may increase risk of complications from influenza which are used to determine eligibility for the study.
1.Primary Outcome
Title Percentage of Participants With Virus Detectable by Quantitative PCR (qPCR) in Nasopharyngeal (NP) Swabs
Hide Description The central laboratory performed a qualitative PCR test on the NP sample from Day 0 in order to confirm influenza infection and to determine the influenza type and subtype. For participants with a positive influenza test result at Day 0 from this qualitative PCR testing, the laboratory then performed qPCR testing of subsequent samples to quantify viral shedding.
Time Frame At Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed was restricted to the 407 participants who had a confirmed positive test for influenza by qPCR in the central laboratory testing and were not in the pilot study for IRC003. 13 participants (5 in the Combination Therapy and 8 in the Oseltamivir Monotherapy) had missing endpoint samples so were excluded from the analysis.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 200 194
Measure Type: Number
Unit of Measure: percentage of participants analyzed
40 50
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combination Therapy, Oseltamivir Monotherapy
Comments Assuming that pooled percentage of participants with virus detectable by PCR at Day 3 is 50%, assuming that the Combination Therapy was better than the Oseltamivir Monotherapy and that the detectable rate in the Combination Therapy was 42.5% compared to 57.5% in the Oseltamivir Monotherapy (a 15% reduction), and assuming 10% subjects with missing qPCR at Day 3, in a two-sided, two-sample 0.05-level t- test with 546 participants combined across both arms, there was 90% power.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments P-value was not adjusted for multiple interim analyses.
Method Z-test, 2-sided
Comments Comparison of randomized arms was based on the normal approximation to the binomial distribution.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10
Confidence Interval (2-Sided) 95%
-19.8 to -0.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5
Estimation Comments The difference in percents was calculated as the percent detectable in the Combination Therapy minus the percent detectable in the Oseltamivir Monotherapy.
2.Secondary Outcome
Title Number of Participants by Virus Detection Status
Hide Description Number of participants who had undetectable values (less than the limit of detection [LOD]), who had values between the LOD and the lower limit of quantification (LLOQ), and who had values ≥LLOQ
Time Frame At Day 0, 3 and 7.
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Primary Efficacy Population (PEP), which included all participants who were randomized properly, had received at least one dose of study drug, and had influenza virus isolated and typed in the qualitative PCR evaluation at Day 0 from central laboratory testing.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 230 224
Measure Type: Count of Participants
Unit of Measure: Participants
Day 0 >=LLOQ
221
  96.1%
200
  89.3%
>=LOD, <LLOQ
4
   1.7%
9
   4.0%
<LOD
5
   2.2%
15
   6.7%
Missing
0
   0.0%
0
   0.0%
Day 3 >=LLOQ
65
  28.3%
87
  38.8%
>=LOD, <LLOQ
22
   9.6%
25
  11.2%
<LOD
134
  58.3%
104
  46.4%
Missing
9
   3.9%
8
   3.6%
Day 7 >=LLOQ
19
   8.3%
24
  10.7%
>=LOD, <LLOQ
4
   1.7%
7
   3.1%
<LOD
193
  83.9%
184
  82.1%
Missing
14
   6.1%
9
   4.0%
3.Secondary Outcome
Title qPCR Viral Shedding
Hide Description Median, 25% and 75% percentile of the value of viral shedding (Results <LOD were imputed as the LOD value, and Results >= LOD, <LLOQ were imputed as the LLOQ value.)
Time Frame At Day 0, 3 and 7
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Primary Efficacy Population (PEP), which included all participants who were randomized properly, had received at least one dose of study drug, and had influenza virus isolated and typed in the qualitative PCR evaluation at Day 0 from central laboratory testing.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 230 224
Median (Inter-Quartile Range)
Unit of Measure: Log10 copies/mL
Day 0
6.4
(5.6 to 7.2)
6.7
(5.1 to 7.7)
Day 3
3.4
(3.2 to 4.2)
3.9
(3.2 to 4.95)
Day 7
3.2
(3.2 to 3.4)
3.2
(3.2 to 3.4)
4.Secondary Outcome
Title Number of Participants Shedding Virus
Hide Description Number of participants with undetectable viral load at both Day 3 and Day 7; detectable at Day 3 and undetectable at Day 7; detectable at Day 7 (irrespective of whether or not detectable at Day 3).
Time Frame At day 3 and 7.
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Primary Efficacy Population (PEP), which included all participants who were randomized properly, had received at least one dose of study drug, and had influenza virus isolated and typed in the qualitative PCR evaluation at Day 0 from central laboratory testing.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 230 224
Measure Type: Count of Participants
Unit of Measure: Participants
Undetectable at both Day 3 and 7
126
  54.8%
95
  42.4%
Detectable at Day 3 and undetectable at Day 7
67
  29.1%
88
  39.3%
Detectable at Day 7
23
  10.0%
30
  13.4%
Missing result at Day 3 and/or Day 7
14
   6.1%
11
   4.9%
5.Secondary Outcome
Title Time to Alleviation of Influenza Clinical Symptoms.
Hide Description The assessed symptoms were cough, nasal obstruction (stuffy nose), sore throat, fatigue, headache, muscle aches, feverishness, rhinorrhea, nausea, vomiting, diarrhea. Duration of clinical symptoms is defined as the time from Day 0 to the first of two successive measurements at which all clinical symptoms are grade 0 (absent) or 1 (mild). A measurement is considered to be the 8AM or 8PM assessment during Days 0 to 7 (so two measurements are obtained per day) and then the daily assessment thereafter. Time will then be calculated in half-days through to Day 7. If a subject’s first two assessments on (baseline assessment and first subsequent diary card assessment) satisfy this criterion, then the duration will be set to zero. For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with symptoms evaluated.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Median (95% Confidence Interval)
Unit of Measure: Days
4.5
(4.0 to 5.0)
4.0
(3.5 to 4.5)
6.Secondary Outcome
Title Time to Absence of Fever
Hide Description Fever was considered present based on the diary cards if a subject reported a maximal temperature ≥38.0°C (for the period since the diary card was previously completed) or reported having taken an antipyretic drug (also for the period since the diary card was previously completed). Otherwise, fever was considered not present during the period since the diary card was previously completed, except that the evaluation was considered missing if either the temperature or the antipyretic drug use entry was not completed on the diary card. The duration of fever was defined as the time from Day 0 to the first of two successive assessments (through to Day 7) or to the first assessment (Day 8 onwards) at which no fever was present according to this definition.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with fever evaluated.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Median (95% Confidence Interval)
Unit of Measure: Days
0.5 [1] 
(NA to NA)
0.5 [1] 
(NA to NA)
[1]
Not estimable
7.Secondary Outcome
Title Time to Resolution of All Symptoms AND Fever
Hide Description The assessed symptoms were cough, nasal obstruction (stuffy nose), sore throat, fatigue, headache, muscle aches, feverishness, rhinorrhea, nausea, vomiting, diarrhea. Fever was considered present based on the diary cards if a subject reported a maximal temperature ≥38.0°C (for the period since the diary card was previously completed) or reported having taken an antipyretic drug (also for the period since the diary card was previously completed). Time to resolution of all clinical symptoms and fever is defined as the time from Day 0 to the first of two successive measurements at which all clinical symptoms are grade 0 (absent) or 1(mild) and no fever >=38.0 C or antipyretic drug is reported. For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with symptoms and fever evaluated.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which includes all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Median (95% Confidence Interval)
Unit of Measure: Days
4.5
(4.0 to 5.0)
4.5
(4.0 to 5.0)
8.Secondary Outcome
Title Time to Feeling as Good as Before the Onset of the Influenza Illness
Hide Description Time to feeling as good as before influenza is defined as time to the first of two successive 'yes' responses to the question of 'feeling as good as you did before you had the flu'.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with question answered.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Median (95% Confidence Interval)
Unit of Measure: Days
7.5
(7.0 to 7.5)
6.5
(6.0 to 7.0)
9.Secondary Outcome
Title Time to Return to Pre-influenza Function
Hide Description Time to return to pre-influenza function is defined as the time from Day 0 to the first of two successive 'Yes' answers to the global assessment question 'Are you functioning as well as you were before you had the flu'.For participants who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with question answered.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Median (95% Confidence Interval)
Unit of Measure: Days
7.0
(6.0 to 7.5)
6.0
(5.0 to 6.5)
10.Secondary Outcome
Title Time to Return of Physical Function to Pre-illness Leve
Hide Description Time to return of physical function to pre-illness level was defined as the time from Day 0 to the first of two successive measurements at which the physical function score equals or is better than the pre-illness score (obtained by recall at enrollment).For subjects who did not have two successive records meeting this criterion, follow-up was censored for analysis purposes at the time of the last but one diary card record with physical function evaluated.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Median (95% Confidence Interval)
Unit of Measure: Days
7.0
(6.0 to 8.0)
6.0
(6.0 to 7.0)
11.Secondary Outcome
Title Percentage of Participants With Clinical Failure at Day 5
Hide Description Clinical failure at Day 5 is defined as the need for continued (non-study) antiviral use after Day 5.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Measure Type: Number
Unit of Measure: percentage of participants analyzed
7.0 7.7
12.Secondary Outcome
Title Percentage of Participants Who Develop Bronchitis, Pneumonia, or Other Complications of Influenza After Day 0.
Hide Description Participants were assessed for the signs/symptoms suggestive of one of the following complications: Sinusitis, Otitis Media ,Bronchitis / Bronchiolitis, Pneumonia and antibiotic use for reason other than above.
Time Frame From treatment initiation to Day 28
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Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug. The categories in the table are not mutually exclusive (because some participants had multiple complications) and the last row of the table summarizes all incidents.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Measure Type: Number
Unit of Measure: percentage of participants analyzed
Sinustis 4.5 4.5
Otitis Media 0.3 1.0
Bronchitis Bronchiolitis 5.7 3.5
Pneumonia 2.2 1.9
Antibiotic use for other reasons 8.6 9.3
At least one complication and/or use of antibiotic 16.6 15.4
13.Secondary Outcome
Title Percentage of Participants Who Required New or Increased Use of Supplemental Oxygen
Hide Description Percentage of participants who required new or increased use of supplemental oxygen
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Measure Type: Number
Unit of Measure: percentage of participants analyzed
1.91 1.6
14.Secondary Outcome
Title Percentage of Participants Who Required Hospitalization.
Hide Description The percentage of participants hospitalized by 28 days was estimated from the Kaplan-Meier curves.
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants analyzed
4.28
(2 to 6.56)
0.98
(-0.12 to 2.08)
15.Secondary Outcome
Title 28-day Mortality
Hide Description Number of deaths
Time Frame From treatment initiation to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Intention To Treat (ITT) Population, which included all participants who were randomized properly and who had received at least one dose of study drug.
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description:

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

Overall Number of Participants Analyzed 314 312
Measure Type: Number
Unit of Measure: participants
0 1
Time Frame Adverse events were collected throughout the conduct of the study; from Day 0 to Day 28
Adverse Event Reporting Description All worsening and new symptoms were evaluated as potential adverse events.If a diagnosis was clinically evident (or subsequently determined), the diagnosis, rather than the individual signs and symptoms or lab abnormalities, were recorded as the AE. All worsening laboratory values were also evaluated as potential adverse events. The DAIDS AE Grading Table (V1.0) was used.
 
Arm/Group Title Combination Therapy Oseltamivir Monotherapy
Hide Arm/Group Description

Drug: Amantadine, Ribavirin, Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg, three capsules of Ribavirin 200 mg for total of 600 mg, and one capsule of Amantadine 100 mg.

Drug: Oseltamivir

Subjects were prescribed the medication twice daily for 5 days, and each dose consisted of one capsule of Oseltamivir 75 mg.

All-Cause Mortality
Combination Therapy Oseltamivir Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   0/314 (0.00%)   1/312 (0.32%) 
Show Serious Adverse Events Hide Serious Adverse Events
Combination Therapy Oseltamivir Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   14/314 (4.46%)   6/312 (1.92%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  0/314 (0.00%)  1/312 (0.32%) 
Cardiac disorders     
Atrial fibrillation  1  1/314 (0.32%)  0/312 (0.00%) 
Atrial tachycardia  1  1/314 (0.32%)  0/312 (0.00%) 
Cardiac failure  1  0/314 (0.00%)  1/312 (0.32%) 
Gastrointestinal disorders     
Diarrhoea  1  2/314 (0.64%)  0/312 (0.00%) 
Diarrhoea haemorrhagic  1  1/314 (0.32%)  0/312 (0.00%) 
Nausea  1  1/314 (0.32%)  0/312 (0.00%) 
Infections and infestations     
Cellulitis  1  1/314 (0.32%)  0/312 (0.00%) 
Gastroenteritis  1  1/314 (0.32%)  0/312 (0.00%) 
Pneumonia  1  1/314 (0.32%)  1/312 (0.32%) 
Injury, poisoning and procedural complications     
Spinal compression fracture  1  1/314 (0.32%)  0/312 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  1/314 (0.32%)  0/312 (0.00%) 
Psychiatric disorders     
Delirium  1  0/314 (0.00%)  1/312 (0.32%) 
Personality change  1  0/314 (0.00%)  1/312 (0.32%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  2/314 (0.64%)  0/312 (0.00%) 
Bronchospasm  1  0/314 (0.00%)  1/312 (0.32%) 
Pulmonary oedema  1  1/314 (0.32%)  0/312 (0.00%) 
Respiratory distress  1  1/314 (0.32%)  0/312 (0.00%) 
Skin and subcutaneous tissue disorders     
Diabetic foot  1  1/314 (0.32%)  0/312 (0.00%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination Therapy Oseltamivir Monotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   148/314 (47.13%)   163/312 (52.24%) 
Gastrointestinal disorders     
Diarrhoea  1  40/314 (12.74%)  52/312 (16.67%) 
Nausea  1  52/314 (16.56%)  50/312 (16.03%) 
Vomiting  1  34/314 (10.83%)  22/312 (7.05%) 
General disorders     
Fatigue  1  18/314 (5.73%)  12/312 (3.85%) 
Pyrexia  1  16/314 (5.10%)  18/312 (5.77%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  17/314 (5.41%)  13/312 (4.17%) 
Nervous system disorders     
Dizziness  1  23/314 (7.32%)  22/312 (7.05%) 
Headache  1  14/314 (4.46%)  19/312 (6.09%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  14/314 (4.46%)  22/312 (7.05%) 
Oropharyngeal pain  1  15/314 (4.78%)  11/312 (3.53%) 
Rhinorrhoea  1  13/314 (4.14%)  17/312 (5.45%) 
Vascular disorders     
Hypertension  1  12/314 (3.82%)  15/312 (4.81%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John Beigel, M.D.
Organization: Leidos Biomedical Research, Inc. is support to the National Institute of Allergy and Infectious Diseases (NIAID)
Phone: 301-451-9881
EMail: jbeigel@niaid.nih.gov
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01227967     History of Changes
Other Study ID Numbers: 10-I-0210
10-I-0210
IRC003
First Submitted: October 22, 2010
First Posted: October 25, 2010
Results First Submitted: May 31, 2017
Results First Posted: July 11, 2017
Last Update Posted: February 4, 2019