Trial Outcomes & Findings for Long-Term Safety Study of Inhaled Insulin: An Up to Four-Year Extension of Therapy in Subjects With Type 1 or Type 2 Diabetes Mellitus (NCT NCT00143247)
NCT ID: NCT00143247
Last Updated: 2010-04-15
Results Overview
Change from Baseline: mean of (value of observed forced expiratory volume in 1 second (FEV1) (liters) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
173 participants
Primary outcome timeframe
Baseline to 126 months
Results posted on
2010-04-15
Participant Flow
Subjects with type 1 or 2 diabetes in 1 of parent Phase 2 protocols (217-102,103,or 104)\& received EXUBERA® (EXU)were enrolled. 173 subjects were screened,assigned to treatment,and treated for at least 1 day.For each subject,data from controlled and extension studies were combined to represent each subject's entire EXU exposure experience.
The objective of the study was to observe,in subjects with long-term exposure to EXUBERA®,pulmonary function over time.For each subject,data from the controlled study (217-102,103,and 104) were combined with data from the respective extension studies as well as the A2171036 extension study to represent each subject's entire EXU exposure experience.
Participant milestones
| Measure |
Inhaled Insulin
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
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|---|---|
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Overall Study
STARTED
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173
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Overall Study
COMPLETED
|
17
|
|
Overall Study
NOT COMPLETED
|
156
|
Reasons for withdrawal
| Measure |
Inhaled Insulin
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
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|---|---|
|
Overall Study
Death
|
8
|
|
Overall Study
Adverse Event
|
19
|
|
Overall Study
Lack of Efficacy
|
3
|
|
Overall Study
Withdrawal by Subject
|
55
|
|
Overall Study
Study terminated by sponsor
|
31
|
|
Overall Study
Protocol Violation
|
15
|
|
Overall Study
Lost to Follow-up
|
12
|
|
Overall Study
following inaccurate lab adverse event
|
1
|
|
Overall Study
Other
|
12
|
Baseline Characteristics
Long-Term Safety Study of Inhaled Insulin: An Up to Four-Year Extension of Therapy in Subjects With Type 1 or Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Inhaled Insulin
n=173 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
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|---|---|
|
Age Continuous
|
46.6 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
103 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 126 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Change from Baseline: mean of (value of observed forced expiratory volume in 1 second (FEV1) (liters) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements.
Outcome measures
| Measure |
Inhaled Insulin
n=156 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
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|---|---|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
3 months (n=154)
|
-0.077 liters
Standard Deviation 0.204
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
6 months (n=149)
|
-0.101 liters
Standard Deviation 0.204
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
12 months (n=138)
|
-0.137 liters
Standard Deviation 0.220
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
18 months (n=123)
|
-0.141 liters
Standard Deviation 0.218
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
24 months (n=116)
|
-0.184 liters
Standard Deviation 0.232
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
30 months (n=108)
|
-0.210 liters
Standard Deviation 0.237
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
36 months (n=101)
|
-0.253 liters
Standard Deviation 0.244
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
42 months (n=92)
|
-0.288 liters
Standard Deviation 0.217
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
48 months (n=88)
|
-0.307 liters
Standard Deviation 0.252
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
54 months (n=83)
|
-0.291 liters
Standard Deviation 0.260
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
60 months (n=75)
|
-0.312 liters
Standard Deviation 0.267
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
66 months (n=70)
|
-0.344 liters
Standard Deviation 0.273
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
72 months (n=67)
|
-0.363 liters
Standard Deviation 0.289
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
78 months (n=61)
|
-0.376 liters
Standard Deviation 0.281
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
84 months (n=57)
|
-0.421 liters
Standard Deviation 0.301
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
90 months (n=56)
|
-0.446 liters
Standard Deviation 0.311
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
96 months (n=54)
|
-0.455 liters
Standard Deviation 0.332
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
102 months (n=50)
|
-0.469 liters
Standard Deviation 0.321
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
108 months (n=42)
|
-0.496 liters
Standard Deviation 0.273
|
|
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
114 months (n=35)
|
-0.510 liters
Standard Deviation 0.281
|
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Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
120 months (n=23)
|
-0.490 liters
Standard Deviation 0.298
|
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Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
126 months (n=11)
|
-0.634 liters
Standard Deviation 0.371
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PRIMARY outcome
Timeframe: baseline to 126 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Change from Baseline: mean of (value of observed Carbon Monoxide Diffusing Capacity (mL/min/mm Hg) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements.
Outcome measures
| Measure |
Inhaled Insulin
n=152 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
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|---|---|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
6 months (n=149)
|
-1.200 mL/min/mm Hg
Standard Deviation 4.358
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
12 months (n=130)
|
-1.262 mL/min/mm Hg
Standard Deviation 4.446
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
18 months (n=115)
|
-1.883 mL/min/mm Hg
Standard Deviation 4.690
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
24 months (n=113)
|
-2.012 mL/min/mm Hg
Standard Deviation 4.821
|
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Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
30 months (n=100)
|
-1.601 mL/min/mm Hg
Standard Deviation 5.816
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
36 months (n=95)
|
-2.122 mL/min/mm Hg
Standard Deviation 5.030
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
42 months (n=86)
|
-2.550 mL/min/mm Hg
Standard Deviation 5.307
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
48 months (n=82)
|
-1.827 mL/min/mm Hg
Standard Deviation 3.623
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
54 months (n=80)
|
-2.118 mL/min/mm Hg
Standard Deviation 3.485
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
60 months (n=70)
|
-2.037 mL/min/mm Hg
Standard Deviation 4.325
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
66 months (n=64)
|
-2.377 mL/min/mm Hg
Standard Deviation 4.168
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
72 months (n=62)
|
-1.401 mL/min/mm Hg
Standard Deviation 5.061
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
78 months (n=59)
|
-1.532 mL/min/mm Hg
Standard Deviation 5.764
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
84 months (n=57)
|
-1.111 mL/min/mm Hg
Standard Deviation 4.672
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
90 months (n=50)
|
-0.919 mL/min/mm Hg
Standard Deviation 4.043
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
96 months (n=52)
|
-0.609 mL/min/mm Hg
Standard Deviation 4.763
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
102 months (n=42)
|
-1.504 mL/min/mm Hg
Standard Deviation 3.514
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
108 months (n=40)
|
-2.397 mL/min/mm Hg
Standard Deviation 4.496
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
114 months (n=35)
|
-2.450 mL/min/mm Hg
Standard Deviation 4.471
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|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
120 months (n=26)
|
-2.028 mL/min/mm Hg
Standard Deviation 3.403
|
|
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
126 months (n=22)
|
-2.126 mL/min/mm Hg
Standard Deviation 3.984
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SECONDARY outcome
Timeframe: Baseline to 126 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Change from Baseline: mean of (value of observed glycosylated hemoglobin (HbA1C) (percent) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements.
Outcome measures
| Measure |
Inhaled Insulin
n=157 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
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|---|---|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
102 months (n=50)
|
-0.77 percent HbA1C
Standard Deviation 1.52
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
3 months (n=155)
|
-0.99 percent HbA1C
Standard Deviation 1.37
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
6 months (n=146)
|
-0.90 percent HbA1C
Standard Deviation 1.58
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|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
12 months (n=136)
|
-0.60 percent HbA1C
Standard Deviation 1.72
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
18 months (n=121)
|
-0.66 percent HbA1C
Standard Deviation 1.61
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|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
24 months (n=115)
|
-0.65 percent HbA1C
Standard Deviation 1.67
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Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
30 months (n=107)
|
-0.67 percent HbA1C
Standard Deviation 1.72
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Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
36 months (n=99)
|
-0.60 percent HbA1C
Standard Deviation 1.73
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Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
42 months (n=93)
|
-0.61 percent HbA1C
Standard Deviation 1.72
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
48 months (n=88)
|
-0.48 percent HbA1C
Standard Deviation 1.64
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
54 months (n=83)
|
-0.50 percent HbA1C
Standard Deviation 1.61
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
60 months (n=75)
|
-0.48 percent HbA1C
Standard Deviation 1.56
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
66 months (n=70)
|
-0.56 percent HbA1C
Standard Deviation 1.82
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
72 months (n=67)
|
-0.61 percent HbA1C
Standard Deviation 1.87
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
78 months (n=62)
|
-0.80 percent HbA1C
Standard Deviation 1.47
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
84 months (n=57)
|
-0.71 percent HbA1C
Standard Deviation 1.26
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
90 months (n=56)
|
-0.75 percent HbA1C
Standard Deviation 1.51
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
96 months (n=54)
|
-0.58 percent HbA1C
Standard Deviation 1.46
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
108 months (n=42)
|
-0.68 percent HbA1C
Standard Deviation 1.51
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
114 months (n=37)
|
-0.78 percent HbA1C
Standard Deviation 1.60
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
120 months (n=31)
|
-0.39 percent HbA1C
Standard Deviation 1.46
|
|
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
126 months (n=23)
|
-0.08 percent HbA1C
Standard Deviation 1.22
|
SECONDARY outcome
Timeframe: 0 to 132 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Number of hypoglycemic events per subject-month. Subject-month determined by time on treatment. Interval of treatment based on elapsed duration of treatment in the controlled \& uncontrolled studies.Overall represents entire duration of treatment. Hypoglycemia: Characteristic symptoms of hypoglycemia with no blood glucose check. Clinical picture must include prompt resolution with food intake, subcutaneous glucagon or intravenous glucose.OR,Characteristic symptoms of hypoglycemia with blood glucose check showing glucose \<=59 mg/dl.OR,Any glucose measurement \<=49 mg/dl,with or without symptoms.
Outcome measures
| Measure |
Inhaled Insulin
n=159 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>72 to 78 months (n=64)
|
1.47 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
0 to 4 weeks (n=159)
|
2.38 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>4 to 8 weeks (n=158)
|
2.10 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>8 to 12 weeks (n=157)
|
1.92 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>12 weeks to 6 months (n=155)
|
1.88 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>6 to12 months (n=149)
|
1.91 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>12 to18 months (n=134)
|
1.63 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>18 to 24 months (n=122)
|
1.96 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>24 to 30 months (n=112)
|
1.99 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>30 to 36 months (n=107)
|
1.78 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>36 to 42 months (n=98)
|
1.54 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>42 to 48 months (n=91)
|
1.47 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>48 to 54 months (n=85)
|
1.36 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>54 to 60 months (n=80)
|
1.38 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>60 to 66 months (n=74)
|
1.32 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>66 to 72 months (n=70)
|
1.42 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>78 to 84 months (n=59)
|
1.74 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>84 to 90 months (n=58)
|
1.63 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>90 to 96 months (n=56)
|
1.67 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>96 to 102 months (n=52)
|
1.52 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>102 to 108 months (n=48)
|
1.16 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>108 to 114 months (n=40)
|
1.51 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>114 to 120 months (n=37)
|
1.41 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>120 to 126 months (n=25)
|
1.13 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
>126 to 132 months (n=18)
|
0.92 events / subject-month
|
|
Hypoglycemic Event Rates by Interval of Exubera Treatment
Overall (n=159)
|
1.65 events / subject-month
|
SECONDARY outcome
Timeframe: 0-132 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Number of severe hypoglycemic events per 100 subject-months.Subject-month determined by time on treatment.Interval of treatment based on elapsed duration of treatment in controlled \& uncontrolled studies.Overall represents entire duration of treatment.A severe hypoglycemic event must have met all 3of following:1.subject unable to treat self.2.subject exhibited 1 or more of neurological symptoms defined in protocol.3.blood glucose must be \<=49 mg/dl if measured.If not measured,clinical manifestations must have been reversed by oral carbohydrates,subcutaneous glucagon,or intravenous glucose.
Outcome measures
| Measure |
Inhaled Insulin
n=159 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>102-108 months (n=48)
|
0.39 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
0-4 weeks (n=159)
|
1.37 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>4-8 weeks (n=158)
|
2.76 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>8-12 weeks (n=157)
|
0.70 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>12 weeks-6months (n=155)
|
2.64 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>6-12 months (n=149)
|
1.07 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>12-18 months (n=134)
|
0.93 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>18-24 months (n=122)
|
0.85 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>24-30 months (n=112)
|
1.07 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>30-36 months (n=107)
|
0.97 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>36-42 months (n=98)
|
0.18 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>42-48 months (n=91)
|
0.19 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>48-54 months (n=85)
|
0.60 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>54-60 months (n=80)
|
0.87 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>60-66 months (n=74)
|
0.47 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>66-72 months (n=70)
|
0.75 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>72-78 months (n=64)
|
0.27 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>78-84 months (n=59)
|
1.14 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>84-90 months (n=58)
|
1.47 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>90-96 months (n=56)
|
0.31 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>96-102 months (n=52)
|
1.32 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>108-114 months (n=40)
|
0.44 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>114-120 months (n=37)
|
0.54 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>120-126 months (n=25)
|
0 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
>126-132 months (n=18)
|
0 severe events / 100 subject-months
|
|
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
Overall (n=159)
|
0.88 severe events / 100 subject-months
|
SECONDARY outcome
Timeframe: 36 months to 126 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Observed values by duration of treatment.
Outcome measures
| Measure |
Inhaled Insulin
n=61 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
36 months (n=31)
|
26.00 percent binding
Full Range 23.95 • Interval 1.5 to 88.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
42 months (n=4)
|
27.00 percent binding
Full Range 15.44 • Interval 4.0 to 37.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
48 months (n=28)
|
19.00 percent binding
Interval 1.5 to 64.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
54 months (n=27)
|
16.00 percent binding
Interval 1.5 to 63.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
60 months (n=26)
|
14.00 percent binding
Interval 1.5 to 83.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
66 months (n=23)
|
16.00 percent binding
Interval 1.5 to 66.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
72 months (n=22)
|
13.00 percent binding
Interval 1.5 to 81.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
78 months (n=24)
|
14.00 percent binding
Interval 3.0 to 84.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
84 months (n=23)
|
16.00 percent binding
Interval 1.5 to 67.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
90 months (n=21)
|
13.00 percent binding
Interval 1.5 to 77.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
96 months (n=23)
|
18.00 percent binding
Interval 1.5 to 77.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
102 months (n=21)
|
14.00 percent binding
Interval 1.5 to 76.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
108 months (n=17)
|
18.00 percent binding
Interval 1.5 to 83.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
114 months (n=15)
|
11.00 percent binding
Interval 1.5 to 65.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
120 months (n=14)
|
8.50 percent binding
Interval 1.5 to 75.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
126 months (n=14)
|
9.00 percent binding
Interval 1.5 to 60.0
|
SECONDARY outcome
Timeframe: 36 to 126 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
observed values by duration of treatment.
Outcome measures
| Measure |
Inhaled Insulin
n=48 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
108 months (n=11)
|
4.00 percent binding
Interval 1.5 to 46.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
36 months (n=22)
|
2.75 percent binding
Full Range 14.89 • Interval 1.5 to 69.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
42 months (n=9)
|
1.50 percent binding
Full Range 12.69 • Interval 1.5 to 40.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
48 months (n=21)
|
1.50 percent binding
Interval 1.5 to 62.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
54 months (n=20)
|
1.50 percent binding
Interval 1.5 to 45.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
60 months (n=17)
|
1.50 percent binding
Interval 1.5 to 82.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
66 months (n=16)
|
1.50 percent binding
Interval 1.5 to 75.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
72 months (n=14)
|
1.50 percent binding
Interval 1.5 to 84.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
78 months (n=14)
|
1.50 percent binding
Interval 1.5 to 61.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
84 months (n=14)
|
1.50 percent binding
Interval 1.5 to 69.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
90 months (n=12)
|
1.50 percent binding
Interval 1.5 to 65.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
96 months (n=12)
|
1.50 percent binding
Interval 1.5 to 55.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
102 months (n=11)
|
1.50 percent binding
Interval 1.5 to 56.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
114 months (n=11)
|
4.00 percent binding
Interval 1.5 to 33.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
120 months (n=10)
|
1.50 percent binding
Interval 1.5 to 32.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
126 months (n=8)
|
1.50 percent binding
Interval 1.5 to 27.0
|
SECONDARY outcome
Timeframe: 6 to 120 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Observed values by duration of treatment.
Outcome measures
| Measure |
Inhaled Insulin
n=57 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
6 months (n=58)
|
1.50 percent binding
Full Range 5.36 • Interval 1.5 to 29.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
12 months (n=48)
|
2.25 percent binding
Interval 1.5 to 55.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
18 months (n=5)
|
10.00 percent binding
Interval 1.5 to 19.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
24 months (n=41)
|
1.50 percent binding
Interval 1.5 to 44.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
30 months (n=4)
|
7.25 percent binding
Interval 1.5 to 28.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
36 months (n=37)
|
1.50 percent binding
Interval 1.5 to 41.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
42 months (n=33)
|
1.50 percent binding
Interval 1.5 to 38.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
48 months (n=32)
|
1.50 percent binding
Interval 1.5 to 43.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
54 months (n=30)
|
1.50 percent binding
Interval 1.5 to 43.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
60 months (n=25)
|
1.50 percent binding
Interval 1.5 to 42.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
66 months (n=30)
|
1.50 percent binding
Interval 1.5 to 40.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
72 months (n=24)
|
1.50 percent binding
Interval 1.5 to 36.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
78 months (n=23)
|
1.50 percent binding
Interval 1.5 to 54.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
84 months (n=20)
|
1.50 percent binding
Interval 1.5 to 41.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
90 months (n=18)
|
1.50 percent binding
Interval 1.5 to 48.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
96 months (n=18)
|
1.50 percent binding
Interval 1.5 to 50.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
102 months (n=14)
|
1.50 percent binding
Interval 1.5 to 36.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
108 months (n=13)
|
1.50 percent binding
Interval 1.5 to 24.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
114 months (n=9)
|
1.50 percent binding
Interval 1.5 to 20.0
|
|
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
120 months (n=6)
|
1.50 percent binding
Interval 1.5 to 5.0
|
SECONDARY outcome
Timeframe: 3 to >=108 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Decliners = decline of ≥15% in forced expiratory volume or ≥20% in carbon monoxide diffusing capacity.
Outcome measures
| Measure |
Inhaled Insulin
n=156 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
3 months (n=154)
|
2 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
6 months (n=151)
|
19 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
12 months (n=138)
|
14 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
18 months (n=123)
|
15 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
24 months (n=116)
|
26 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
30 months (n=108)
|
26 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
36 months (n=101)
|
30 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
42 months (n=92)
|
30 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
48 months (n=88)
|
24 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
54 months (n=83)
|
22 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
60 months (n=75)
|
28 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
66 months (n=70)
|
25 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
72 months (n=67)
|
19 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
78 months (n=61)
|
21 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
84 months (n=57)
|
26 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
90 months (n=56)
|
25 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
96 months (n=54)
|
21 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
102 months (n=50)
|
25 participants
|
|
Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment
>=108 months (n=42)
|
29 participants
|
SECONDARY outcome
Timeframe: 3 to >=108 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Decliners at particular timepoint were defined as any decline of ≥15% in forced expiratory volume.
Outcome measures
| Measure |
Inhaled Insulin
n=156 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
3 months (n=154)
|
2 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
6 months (n=149)
|
5 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
12 months (n=138)
|
6 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
18 months (n=123)
|
5 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
24 months (n=116)
|
9 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
30 months (n=108)
|
14 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
36 months (n=101)
|
18 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
42 months (n=92)
|
18 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
48 months (n=88)
|
19 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
54 months (n=83)
|
14 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
60 months (n=75)
|
21 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
66 months (n=70)
|
19 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
72 months (n=67)
|
17 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
78 months (n=61)
|
17 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
84 months (n=57)
|
21 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
90 months (n=56)
|
24 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
96 months (n=54)
|
19 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
102 months (n=50)
|
24 participants
|
|
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
>=108 months (n=42)
|
27 participants
|
SECONDARY outcome
Timeframe: 6 to >=108 monthsPopulation: 173 subjects received at least one treatment. The safety analysis set (subjects who received at least one dose of EXU treatment) were included in analysis. n = subjects who had outcome measure data available at particular time points. There was no imputation for missing data.
Decliners at particular timepoint were defined as any decline of ≥20% in carbon monoxide diffusing capacity.
Outcome measures
| Measure |
Inhaled Insulin
n=152 Participants
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
6 months (n=149)
|
16 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
12 months (n=130)
|
8 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
18 months (n=115)
|
13 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
24 months (n=113)
|
21 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
30 months (n=100)
|
14 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
36 months (n=95)
|
14 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
42 months (n=86)
|
13 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
48 months (n=82)
|
11 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
54 months (n=80)
|
11 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
60 months (n=70)
|
10 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
66 months (n=64)
|
11 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
72 months (n=62)
|
8 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
78 months (n=59)
|
11 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
84 months (n=57)
|
10 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
90 months (n=50)
|
5 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
96 months (n=52)
|
4 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
102 months (n=42)
|
4 participants
|
|
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
>=108 months (n=41)
|
13 participants
|
Adverse Events
Inhaled Insulin
Serious events: 63 serious events
Other events: 172 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Inhaled Insulin
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Gastrointestinal disorders
Impacted colon
|
0.58%
1/173
|
|
Blood and lymphatic system disorders
Anemia
|
1.2%
2/173
|
|
Cardiac disorders
Acute myocardial infarction
|
1.7%
3/173
|
|
Cardiac disorders
Angina pectoris
|
1.2%
2/173
|
|
Cardiac disorders
Angina unstable
|
0.58%
1/173
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.58%
1/173
|
|
Cardiac disorders
Bradycardia
|
1.2%
2/173
|
|
Cardiac disorders
Cardiac failure congestive
|
1.7%
3/173
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.58%
1/173
|
|
Cardiac disorders
Coronary artery disease
|
5.8%
10/173
|
|
Cardiac disorders
Coronary artery occlusion
|
1.2%
2/173
|
|
Cardiac disorders
Coronary artery stenosis
|
0.58%
1/173
|
|
Cardiac disorders
Myocardial infarction
|
2.9%
5/173
|
|
Cardiac disorders
Myocardial ischaemia
|
0.58%
1/173
|
|
Cardiac disorders
Tachycardia
|
0.58%
1/173
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Vertigo
|
0.58%
1/173
|
|
Endocrine disorders
Goitre
|
0.58%
1/173
|
|
Eye disorders
Vitreous haemorrhage
|
0.58%
1/173
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.58%
1/173
|
|
Gastrointestinal disorders
Food poisoning
|
0.58%
1/173
|
|
Gastrointestinal disorders
Haemorrhagic ascites
|
0.58%
1/173
|
|
Gastrointestinal disorders
Nausea
|
0.58%
1/173
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.58%
1/173
|
|
Gastrointestinal disorders
Vomiting
|
0.58%
1/173
|
|
General disorders
Chest pain
|
3.5%
6/173
|
|
General disorders
Impaired healing
|
0.58%
1/173
|
|
General disorders
Non-cardiac chest pain
|
0.58%
1/173
|
|
General disorders
Pain
|
0.58%
1/173
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.2%
2/173
|
|
Hepatobiliary disorders
Jaundice
|
0.58%
1/173
|
|
Infections and infestations
Abdominal wall abscess
|
0.58%
1/173
|
|
Infections and infestations
Bronchitis
|
0.58%
1/173
|
|
Infections and infestations
Cellulitis
|
0.58%
1/173
|
|
Infections and infestations
Cholecystitis infective
|
0.58%
1/173
|
|
Infections and infestations
Diverticulitis
|
0.58%
1/173
|
|
Infections and infestations
Gastroenteritis
|
0.58%
1/173
|
|
Infections and infestations
Localised infection
|
0.58%
1/173
|
|
Infections and infestations
Periorbital cellulitis
|
0.58%
1/173
|
|
Infections and infestations
Pneumonia
|
1.2%
2/173
|
|
Infections and infestations
Pyelonephritis
|
0.58%
1/173
|
|
Infections and infestations
Urosepsis
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Laceration
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Respiratory fume inhalation disorder
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Rib fracture
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
2.3%
4/173
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.58%
1/173
|
|
Investigations
Hepatic enzyme increased
|
0.58%
1/173
|
|
Investigations
Oxygen saturation decreased
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Spondylitis
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.2%
2/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer female
|
1.2%
2/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system lympoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.58%
1/173
|
|
Nervous system disorders
Cerebrovascular accident
|
1.2%
2/173
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.58%
1/173
|
|
Nervous system disorders
Loss of consciousness
|
0.58%
1/173
|
|
Nervous system disorders
Paraplegia
|
0.58%
1/173
|
|
Nervous system disorders
Syncope
|
1.2%
2/173
|
|
Nervous system disorders
Transient ischaemic attack
|
0.58%
1/173
|
|
Renal and urinary disorders
Dysuria
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Fallopian tube cyst
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Fallopian tube disorder
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Ovarian cyst
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Pelvic peritoneal adhesions
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.58%
1/173
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
0.58%
1/173
|
|
Vascular disorders
Aortic stenosis
|
0.58%
1/173
|
|
Vascular disorders
Arterial thrombosis
|
0.58%
1/173
|
|
Vascular disorders
Arterial thrombosis limb
|
0.58%
1/173
|
|
Vascular disorders
Thrombosis
|
0.58%
1/173
|
Other adverse events
| Measure |
Inhaled Insulin
Open label EXUBERA® (EXU; inhaled insulin), no comparator. At all times in the trial, each subject had an individualized recommended insulin dose for each of the dosing times. Initial recommended doses for EXU were based on the subject's weight, any previous responses to insulin, and other factors noted in the protocol.
|
|---|---|
|
Nervous system disorders
Areflexia
|
0.58%
1/173
|
|
Nervous system disorders
Burning sensation
|
2.3%
4/173
|
|
Blood and lymphatic system disorders
Anaemia
|
4.0%
7/173
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.58%
1/173
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
2.9%
5/173
|
|
Cardiac disorders
Acute myocardial infarction
|
1.7%
3/173
|
|
Cardiac disorders
Angina pectoris
|
2.3%
4/173
|
|
Cardiac disorders
Angina unstable
|
0.58%
1/173
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.58%
1/173
|
|
Cardiac disorders
Bradycardia
|
1.2%
2/173
|
|
Cardiac disorders
Bundle branch block right
|
0.58%
1/173
|
|
Cardiac disorders
Cardiac aneurysm
|
0.58%
1/173
|
|
Cardiac disorders
Cardiac failure congestive
|
1.7%
3/173
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.58%
1/173
|
|
Cardiac disorders
Cardiomegaly
|
2.3%
4/173
|
|
Cardiac disorders
Coronary artery disease
|
8.1%
14/173
|
|
Cardiac disorders
Coronary artery occlusion
|
1.2%
2/173
|
|
Cardiac disorders
Coronary artery stenosis
|
0.58%
1/173
|
|
Cardiac disorders
Left atrial dilatation
|
0.58%
1/173
|
|
Cardiac disorders
Myocardial infarction
|
2.9%
5/173
|
|
Cardiac disorders
Myocardial ischaemia
|
0.58%
1/173
|
|
Cardiac disorders
Palpitations
|
6.4%
11/173
|
|
Cardiac disorders
Sinus arrhythmia
|
0.58%
1/173
|
|
Cardiac disorders
Sinus tachycardia
|
0.58%
1/173
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.58%
1/173
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.58%
1/173
|
|
Cardiac disorders
Tachycardia
|
3.5%
6/173
|
|
Cardiac disorders
Ventricular extrasystoles
|
1.2%
2/173
|
|
Congenital, familial and genetic disorders
Familial tremor
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Auricular swelling
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Cerumen impaction
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Deafness
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Deafness unilateral
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Ear canal erythema
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Ear congestion
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Ear discomfort
|
4.0%
7/173
|
|
Ear and labyrinth disorders
Ear disorder
|
1.7%
3/173
|
|
Ear and labyrinth disorders
Ear pain
|
6.9%
12/173
|
|
Ear and labyrinth disorders
Eustachian tube dysfunction
|
1.2%
2/173
|
|
Ear and labyrinth disorders
Hypoacusis
|
1.2%
2/173
|
|
Ear and labyrinth disorders
Meniere's disease
|
1.7%
3/173
|
|
Ear and labyrinth disorders
Motion sickness
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Otorrhoea
|
1.2%
2/173
|
|
Ear and labyrinth disorders
Tinnitus
|
2.3%
4/173
|
|
Ear and labyrinth disorders
Tympanic membrane disorder
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
0.58%
1/173
|
|
Ear and labyrinth disorders
Vertigo
|
4.0%
7/173
|
|
Endocrine disorders
Androgen deficiency
|
0.58%
1/173
|
|
Endocrine disorders
Goitre
|
1.7%
3/173
|
|
Endocrine disorders
Hypothyroidism
|
2.9%
5/173
|
|
Endocrine disorders
Thyroid pain
|
0.58%
1/173
|
|
Eye disorders
Cataract
|
5.2%
9/173
|
|
Eye disorders
Cataract nuclear
|
1.2%
2/173
|
|
Eye disorders
Conjunctival haemorrhage
|
0.58%
1/173
|
|
Eye disorders
Conjunctivitis
|
2.3%
4/173
|
|
Eye disorders
Diabetic retinopathy
|
8.7%
15/173
|
|
Eye disorders
Diplopia
|
1.2%
2/173
|
|
Eye disorders
Dry eye
|
1.2%
2/173
|
|
Eye disorders
Eye allergy
|
0.58%
1/173
|
|
Eye disorders
Eye discharge
|
1.2%
2/173
|
|
Eye disorders
Eye haemorrhage
|
1.7%
3/173
|
|
Eye disorders
Eye inflammation
|
0.58%
1/173
|
|
Eye disorders
Eye irritation
|
1.2%
2/173
|
|
Eye disorders
Eye movement disorder
|
1.2%
2/173
|
|
Eye disorders
Eye pain
|
0.58%
1/173
|
|
Eye disorders
Glaucoma
|
2.3%
4/173
|
|
Eye disorders
Hyphaema
|
0.58%
1/173
|
|
Eye disorders
Iridocyclitis
|
0.58%
1/173
|
|
Eye disorders
Lacrimation increased
|
1.2%
2/173
|
|
Eye disorders
Macular degeneration
|
0.58%
1/173
|
|
Eye disorders
Macular oedema
|
1.2%
2/173
|
|
Eye disorders
Myodesopsia
|
1.2%
2/173
|
|
Eye disorders
Photopsia
|
1.2%
2/173
|
|
Eye disorders
Retinal aneurysm
|
1.2%
2/173
|
|
Eye disorders
Retinal detachment
|
0.58%
1/173
|
|
Eye disorders
Retinal haemorrhage
|
0.58%
1/173
|
|
Eye disorders
Retinopathy
|
3.5%
6/173
|
|
Eye disorders
Scotoma
|
0.58%
1/173
|
|
Eye disorders
Vision blurred
|
11.6%
20/173
|
|
Eye disorders
Visual acuity reduced
|
0.58%
1/173
|
|
Eye disorders
Visual impairment
|
1.2%
2/173
|
|
Eye disorders
Vitreous haemorrhage
|
1.2%
2/173
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.2%
9/173
|
|
Gastrointestinal disorders
Abdominal distension
|
1.2%
2/173
|
|
Gastrointestinal disorders
Abdominal pain
|
11.0%
19/173
|
|
Gastrointestinal disorders
Abdominal pain lower
|
2.9%
5/173
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.0%
19/173
|
|
Gastrointestinal disorders
Breath odour
|
0.58%
1/173
|
|
Gastrointestinal disorders
Colitis
|
0.58%
1/173
|
|
Gastrointestinal disorders
Colonic Polyp
|
1.7%
3/173
|
|
Gastrointestinal disorders
Constipation
|
10.4%
18/173
|
|
Gastrointestinal disorders
Dental caries
|
3.5%
6/173
|
|
Gastrointestinal disorders
Diarrhoea
|
26.0%
45/173
|
|
Gastrointestinal disorders
Diverticulum
|
1.7%
3/173
|
|
Gastrointestinal disorders
Dry mouth
|
2.9%
5/173
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.58%
1/173
|
|
Gastrointestinal disorders
Duodenogastric reflux
|
1.2%
2/173
|
|
Gastrointestinal disorders
Dyspepsia
|
12.1%
21/173
|
|
Gastrointestinal disorders
Dysphagia
|
1.2%
2/173
|
|
Gastrointestinal disorders
Faecal incontinence
|
0.58%
1/173
|
|
Gastrointestinal disorders
Faeces discoloured
|
0.58%
1/173
|
|
Gastrointestinal disorders
Flatulence
|
1.2%
2/173
|
|
Gastrointestinal disorders
Food poisoning
|
3.5%
6/173
|
|
Gastrointestinal disorders
Frequent bowel movements
|
0.58%
1/173
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.58%
1/173
|
|
Gastrointestinal disorders
Gastritis
|
1.2%
2/173
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.58%
1/173
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
9.8%
17/173
|
|
Gastrointestinal disorders
Gingival pain
|
1.7%
3/173
|
|
Gastrointestinal disorders
Gingival recession
|
0.58%
1/173
|
|
Gastrointestinal disorders
Gingival swelling
|
0.58%
1/173
|
|
Gastrointestinal disorders
Gingivitis
|
1.7%
3/173
|
|
Gastrointestinal disorders
Glossitis
|
0.58%
1/173
|
|
Gastrointestinal disorders
Haematochezia
|
0.58%
1/173
|
|
Gastrointestinal disorders
Haemorrhagic ascites
|
0.58%
1/173
|
|
Gastrointestinal disorders
Haemorrhoids
|
4.0%
7/173
|
|
Gastrointestinal disorders
Hiatus hernia
|
1.2%
2/173
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
2.3%
4/173
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
1.7%
3/173
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.58%
1/173
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.58%
1/173
|
|
Gastrointestinal disorders
Lip blister
|
1.2%
2/173
|
|
Gastrointestinal disorders
Lip disorder
|
0.58%
1/173
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.58%
1/173
|
|
Gastrointestinal disorders
Nausea
|
27.7%
48/173
|
|
Gastrointestinal disorders
Paraesthesia oral
|
2.3%
4/173
|
|
Gastrointestinal disorders
Parotid gland enlargement
|
0.58%
1/173
|
|
Gastrointestinal disorders
Periodontal disease
|
1.7%
3/173
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.58%
1/173
|
|
Gastrointestinal disorders
Rectal polyp
|
1.2%
2/173
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.58%
1/173
|
|
Gastrointestinal disorders
Retching
|
1.2%
2/173
|
|
Gastrointestinal disorders
Stomach discomfort
|
4.0%
7/173
|
|
Gastrointestinal disorders
Swollen tongue
|
0.58%
1/173
|
|
Gastrointestinal disorders
Tongue discolouration
|
1.2%
2/173
|
|
Gastrointestinal disorders
Tongue disorder
|
1.2%
2/173
|
|
Gastrointestinal disorders
Tooth impacted
|
0.58%
1/173
|
|
Gastrointestinal disorders
Tooth loss
|
0.58%
1/173
|
|
Gastrointestinal disorders
Toothache
|
10.4%
18/173
|
|
Gastrointestinal disorders
Umbilical hernia
|
1.2%
2/173
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.58%
1/173
|
|
Gastrointestinal disorders
Vomiting
|
13.9%
24/173
|
|
General disorders
Asthenia
|
23.7%
41/173
|
|
General disorders
Catheter site inflammation
|
0.58%
1/173
|
|
General disorders
Chest discomfort
|
2.9%
5/173
|
|
General disorders
Chest pain
|
13.3%
23/173
|
|
General disorders
Chills
|
1.7%
3/173
|
|
General disorders
Cyst
|
1.2%
2/173
|
|
General disorders
Discomfort
|
0.58%
1/173
|
|
General disorders
Face oedema
|
1.2%
2/173
|
|
General disorders
Fatigue
|
22.0%
38/173
|
|
General disorders
Feeling abnormal
|
1.7%
3/173
|
|
General disorders
Feeling cold
|
1.7%
3/173
|
|
General disorders
Feeling hot
|
1.7%
3/173
|
|
General disorders
Feeling jittery
|
5.2%
9/173
|
|
General disorders
Generalised oedema
|
4.0%
7/173
|
|
General disorders
Hunger
|
13.9%
24/173
|
|
General disorders
Ill-defined disorder
|
0.58%
1/173
|
|
General disorders
Impaired healing
|
0.58%
1/173
|
|
General disorders
Influenza like illness
|
1.7%
3/173
|
|
General disorders
Injection site pain
|
0.58%
1/173
|
|
General disorders
Injection site pruritus
|
0.58%
1/173
|
|
General disorders
Irritability
|
2.9%
5/173
|
|
General disorders
Malaise
|
4.6%
8/173
|
|
General disorders
Non-cardiac chest pain
|
0.58%
1/173
|
|
General disorders
Oedema
|
1.7%
3/173
|
|
General disorders
Oedema peripheral
|
19.7%
34/173
|
|
General disorders
Pain
|
8.1%
14/173
|
|
General disorders
Peripheral coldness
|
0.58%
1/173
|
|
General disorders
Pitting oedema
|
0.58%
1/173
|
|
General disorders
Pyrexia
|
6.9%
12/173
|
|
General disorders
Sensation of foreign body
|
1.2%
2/173
|
|
General disorders
Sluggishness
|
1.7%
3/173
|
|
General disorders
Temperature intolerance
|
0.58%
1/173
|
|
General disorders
Thirst
|
2.3%
4/173
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.7%
3/173
|
|
Hepatobiliary disorders
Hepatic steatosis
|
1.2%
2/173
|
|
Hepatobiliary disorders
Jaundice
|
0.58%
1/173
|
|
Hepatobiliary disorders
Liver disorder
|
0.58%
1/173
|
|
Immune system disorders
Anaphylactic reaction
|
0.58%
1/173
|
|
Immune system disorders
Drug hypersensitivity
|
0.58%
1/173
|
|
Immune system disorders
Hypersensitivity
|
4.6%
8/173
|
|
Immune system disorders
Latex allergy
|
0.58%
1/173
|
|
Immune system disorders
Seasonal allergy
|
11.6%
20/173
|
|
Infections and infestations
Abdominal wall abscess
|
0.58%
1/173
|
|
Infections and infestations
Abscess limb
|
1.2%
2/173
|
|
Infections and infestations
Acarodermatitis
|
0.58%
1/173
|
|
Infections and infestations
Acute sinusitis
|
0.58%
1/173
|
|
Infections and infestations
Breast abscess
|
0.58%
1/173
|
|
Infections and infestations
Bronchitis
|
17.3%
30/173
|
|
Infections and infestations
Candidiasis
|
0.58%
1/173
|
|
Infections and infestations
Catheter related infection
|
0.58%
1/173
|
|
Infections and infestations
Catheter site infection
|
0.58%
1/173
|
|
Infections and infestations
Cellulitis
|
4.0%
7/173
|
|
Infections and infestations
Cholecystitis infective
|
0.58%
1/173
|
|
Infections and infestations
Chronic sinusitis
|
0.58%
1/173
|
|
Infections and infestations
Conjunctivitis infective
|
0.58%
1/173
|
|
Infections and infestations
Cystitis
|
2.9%
5/173
|
|
Infections and infestations
Diverticulitis
|
1.2%
2/173
|
|
Infections and infestations
Ear infection
|
1.7%
3/173
|
|
Infections and infestations
Erythema infectiosum
|
0.58%
1/173
|
|
Infections and infestations
Eye infection
|
0.58%
1/173
|
|
Infections and infestations
Folliculitis
|
1.2%
2/173
|
|
Infections and infestations
Fungal infection
|
3.5%
6/173
|
|
Infections and infestations
Fungal skin infection
|
2.3%
4/173
|
|
Infections and infestations
Furuncle
|
4.0%
7/173
|
|
Infections and infestations
Gastric infection
|
0.58%
1/173
|
|
Infections and infestations
Gastroenteritis
|
9.2%
16/173
|
|
Infections and infestations
Gastroenteritis viral
|
18.5%
32/173
|
|
Infections and infestations
Genital infection fungal
|
0.58%
1/173
|
|
Infections and infestations
Groin Abscess
|
0.58%
1/173
|
|
Infections and infestations
Herpes simplex
|
0.58%
1/173
|
|
Infections and infestations
Herpes zosters
|
4.0%
7/173
|
|
Infections and infestations
Hordeolum
|
1.7%
3/173
|
|
Infections and infestations
Infected cyst
|
0.58%
1/173
|
|
Infections and infestations
Infected sebaceous cyst
|
1.2%
2/173
|
|
Infections and infestations
Infected skin ulcer
|
0.58%
1/173
|
|
Infections and infestations
Infection
|
2.3%
4/173
|
|
Infections and infestations
Infectious mononucleosis
|
0.58%
1/173
|
|
Infections and infestations
Influenza
|
28.9%
50/173
|
|
Infections and infestations
Kidney infection
|
1.2%
2/173
|
|
Infections and infestations
Labyrinthitis
|
2.3%
4/173
|
|
Infections and infestations
Laryngitis
|
4.0%
7/173
|
|
Infections and infestations
Localised infection
|
5.8%
10/173
|
|
Infections and infestations
Lower respiratory tract infection
|
3.5%
6/173
|
|
Infections and infestations
Lymph gland infection
|
0.58%
1/173
|
|
Infections and infestations
Gingival infection
|
2.9%
5/173
|
|
Infections and infestations
Nail bed infection
|
1.2%
2/173
|
|
Infections and infestations
Nasopharyngitis
|
19.7%
34/173
|
|
Infections and infestations
Onychomycosis
|
6.4%
11/173
|
|
Infections and infestations
Oral herpes
|
3.5%
6/173
|
|
Infections and infestations
Osteomyelitis
|
0.58%
1/173
|
|
Infections and infestations
Otitis externa
|
2.9%
5/173
|
|
Infections and infestations
Otitis media
|
6.4%
11/173
|
|
Infections and infestations
Paronychia
|
1.2%
2/173
|
|
Infections and infestations
Penile infection
|
0.58%
1/173
|
|
Infections and infestations
Periorbital cellulitis
|
0.58%
1/173
|
|
Infections and infestations
Pharyngitis
|
9.8%
17/173
|
|
Infections and infestations
Pharyngitis streptococcal
|
5.2%
9/173
|
|
Infections and infestations
Pneumonia
|
5.8%
10/173
|
|
Infections and infestations
Postoperative wound infection
|
1.2%
2/173
|
|
Infections and infestations
Pyelonephritis
|
1.2%
2/173
|
|
Infections and infestations
Recurring skin boils
|
0.58%
1/173
|
|
Infections and infestations
Respiratory tract infection
|
0.58%
1/173
|
|
Infections and infestations
Rhinitis
|
4.0%
7/173
|
|
Infections and infestations
Scrotal abscess
|
0.58%
1/173
|
|
Infections and infestations
Sinusitis
|
19.1%
33/173
|
|
Infections and infestations
Skin infection
|
0.58%
1/173
|
|
Infections and infestations
Soft tissue infection
|
0.58%
1/173
|
|
Infections and infestations
Subcutaneous abscess
|
0.58%
1/173
|
|
Infections and infestations
Tinea infection
|
0.58%
1/173
|
|
Infections and infestations
Tinea pedis
|
3.5%
6/173
|
|
Infections and infestations
Tonsillitis
|
1.2%
2/173
|
|
Infections and infestations
Tooth abscess
|
5.8%
10/173
|
|
Infections and infestations
Tooth infection
|
4.6%
8/173
|
|
Infections and infestations
Upper respiratory tract infection
|
59.0%
102/173
|
|
Infections and infestations
Urinary tract infection
|
15.0%
26/173
|
|
Infections and infestations
Urosepsis
|
0.58%
1/173
|
|
Infections and infestations
Vaginal infection
|
2.3%
4/173
|
|
Infections and infestations
Vaginitis bacterial
|
0.58%
1/173
|
|
Infections and infestations
Viral infection
|
5.2%
9/173
|
|
Infections and infestations
Viral pharyngitis
|
0.58%
1/173
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.58%
1/173
|
|
Infections and infestations
Vulval abscess
|
0.58%
1/173
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
7.5%
13/173
|
|
Infections and infestations
Wound infection
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Back injury
|
3.5%
6/173
|
|
Injury, poisoning and procedural complications
Barotitis media
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Burns second degree
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Burns third degree
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Cartilage injury
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Contusion
|
9.2%
16/173
|
|
Injury, poisoning and procedural complications
Device failure
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Epicondylitis
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Excoriation
|
11.0%
19/173
|
|
Injury, poisoning and procedural complications
Eye injury
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Foot fracture
|
6.4%
11/173
|
|
Injury, poisoning and procedural complications
Hand fracture
|
2.3%
4/173
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Incision site pain
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Injury
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Injury corneal
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Joint injury
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Joint sprain
|
6.4%
11/173
|
|
Injury, poisoning and procedural complications
Laceration
|
5.2%
9/173
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Limb injury
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Lung injury
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Muscle injury
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Muscle strain
|
6.9%
12/173
|
|
Injury, poisoning and procedural complications
Open fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Procedural pain
|
4.6%
8/173
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Respiratory fume inhalation disorder
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Rib fracture
|
3.5%
6/173
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
2.9%
5/173
|
|
Injury, poisoning and procedural complications
Skeletal injury
|
3.5%
6/173
|
|
Injury, poisoning and procedural complications
Skin laceration
|
4.6%
8/173
|
|
Injury, poisoning and procedural complications
Stress fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Sunburn
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Tendon injury
|
1.2%
2/173
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Thermal burn
|
4.6%
8/173
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.58%
1/173
|
|
Injury, poisoning and procedural complications
Wound
|
1.7%
3/173
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.58%
1/173
|
|
Investigations
Aspartate aminotransferase increased
|
1.2%
2/173
|
|
Investigations
Blood cholesterol increased
|
0.58%
1/173
|
|
Investigations
Blood pressure increased
|
2.9%
5/173
|
|
Investigations
Blood testosterone decreased
|
1.2%
2/173
|
|
Investigations
Blood urine present
|
0.58%
1/173
|
|
Investigations
Bone density decreased
|
0.58%
1/173
|
|
Investigations
Cardiac murmur
|
0.58%
1/173
|
|
Investigations
Cardiac stress test abnormal
|
0.58%
1/173
|
|
Investigations
Carotid bruit
|
0.58%
1/173
|
|
Investigations
Chest X-ray abnormal
|
0.58%
1/173
|
|
Investigations
Culture
|
0.58%
1/173
|
|
Investigations
Full blood count decreased
|
0.58%
1/173
|
|
Investigations
Glycosylated haemoglobin
|
0.58%
1/173
|
|
Investigations
Heart rate increased
|
3.5%
6/173
|
|
Investigations
Heart rate irregular
|
1.2%
2/173
|
|
Investigations
Hepatic enzyme increased
|
0.58%
1/173
|
|
Investigations
Occult blood positive
|
1.2%
2/173
|
|
Investigations
Oxygen saturation decreased
|
0.58%
1/173
|
|
Investigations
Platelet count decreased
|
1.2%
2/173
|
|
Investigations
Pulmonary function test decreased
|
1.2%
2/173
|
|
Investigations
Pulse abnormal
|
0.58%
1/173
|
|
Investigations
Smear cervix abnormal
|
0.58%
1/173
|
|
Investigations
Urine analysis abnormal
|
0.58%
1/173
|
|
Investigations
Vitamin B12 decreased
|
0.58%
1/173
|
|
Investigations
Weight increased
|
1.2%
2/173
|
|
Investigations
White blood cell count decreased
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Anorexia
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Dehydration
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Diabetic foot
|
1.2%
2/173
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Fluid retention
|
1.2%
2/173
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
2.9%
5/173
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.5%
6/173
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.2%
2/173
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
4.0%
7/173
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
72.3%
125/173
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.3%
4/173
|
|
Metabolism and nutrition disorders
Ketosis
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
0.58%
1/173
|
|
Metabolism and nutrition disorders
Polydipsia
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
30.1%
52/173
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
3.5%
6/173
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
1.7%
3/173
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
24.3%
42/173
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
2.9%
5/173
|
|
Musculoskeletal and connective tissue disorders
Coccydynia
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Dupuytren's contracture
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
4.0%
7/173
|
|
Musculoskeletal and connective tissue disorders
Fibromyalgia
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
3.5%
6/173
|
|
Musculoskeletal and connective tissue disorders
Joint contracture
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
1.7%
3/173
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
1.7%
3/173
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.3%
4/173
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Monarthritis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Muscle disorder
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.4%
18/173
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.7%
3/173
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
8.1%
14/173
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
2.3%
4/173
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
13.3%
23/173
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
2.3%
4/173
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.4%
11/173
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.6%
8/173
|
|
Musculoskeletal and connective tissue disorders
Nodule on extremity
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.3%
4/173
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
28.3%
49/173
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Polyarthritis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Sacroiliitis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Spondylitis
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Tendon disorder
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
11.0%
19/173
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis
|
1.2%
2/173
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis stenosans
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Trigger finger
|
2.9%
5/173
|
|
Musculoskeletal and connective tissue disorders
Upper extremity mass
|
0.58%
1/173
|
|
Nervous system disorders
CARPAL TUNNEL SYNDROME - RIGHT WRIST
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
DECREASED BREATHING BILATERALLY
|
0.58%
1/173
|
|
Gastrointestinal disorders
DRY, PEELING LIPS
|
0.58%
1/173
|
|
Gastrointestinal disorders
IMPACTED COLON
|
0.58%
1/173
|
|
Eye disorders
LIGHT SENSITIVE VISION
|
0.58%
1/173
|
|
Eye disorders
PROGRESSION OF PROLIFERATIVE DIABETIC RETINOPATHY OF LEFT EYE
|
0.58%
1/173
|
|
Eye disorders
PROGRESSION OF PROLIFERATIVE DIABETIC RETINOPATHY RIGHT EYE
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon
|
1.7%
3/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
1.7%
3/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer female
|
1.2%
2/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system lymphoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibrous histiocytoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
1.2%
2/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
1.7%
3/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
1.2%
2/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
1.7%
3/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.58%
1/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
1.2%
2/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
1.2%
2/173
|
|
Nervous system disorders
Carpal tunnel syndrome
|
5.8%
10/173
|
|
Nervous system disorders
Cerebrovascular accident
|
1.2%
2/173
|
|
Nervous system disorders
Cognitive disorder
|
0.58%
1/173
|
|
Nervous system disorders
Coordination abnormal
|
0.58%
1/173
|
|
Nervous system disorders
Diabetic neuropathy
|
1.2%
2/173
|
|
Nervous system disorders
Disturbance in attention
|
2.9%
5/173
|
|
Nervous system disorders
Dizziness
|
26.6%
46/173
|
|
Nervous system disorders
Dizziness postural
|
0.58%
1/173
|
|
Nervous system disorders
Dysgeusia
|
0.58%
1/173
|
|
Nervous system disorders
Facial palsy
|
1.2%
2/173
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.58%
1/173
|
|
Nervous system disorders
Head discomfort
|
0.58%
1/173
|
|
Nervous system disorders
Headache
|
26.0%
45/173
|
|
Nervous system disorders
Hyperaesthesia
|
0.58%
1/173
|
|
Nervous system disorders
Hypoaesthesia
|
15.0%
26/173
|
|
Nervous system disorders
IIIrd nerve paralysis
|
0.58%
1/173
|
|
Nervous system disorders
Lethargy
|
5.2%
9/173
|
|
Nervous system disorders
Loss of consciousness
|
1.2%
2/173
|
|
Nervous system disorders
Lumbar radiculopathy
|
0.58%
1/173
|
|
Nervous system disorders
Memory impairment
|
1.7%
3/173
|
|
Nervous system disorders
Mental impairment
|
1.2%
2/173
|
|
Nervous system disorders
Migraine
|
2.3%
4/173
|
|
Nervous system disorders
Morton's neuralgia
|
0.58%
1/173
|
|
Nervous system disorders
Nerve compression
|
1.7%
3/173
|
|
Nervous system disorders
Neuralgia
|
1.7%
3/173
|
|
Nervous system disorders
Paraesthesia
|
11.6%
20/173
|
|
Nervous system disorders
Paraplegia
|
0.58%
1/173
|
|
Nervous system disorders
Parkinson's disease
|
0.58%
1/173
|
|
Nervous system disorders
Polyneuropathy
|
0.58%
1/173
|
|
Nervous system disorders
Poor quality sleep
|
0.58%
1/173
|
|
Nervous system disorders
Sciatic nerve neuropathy
|
0.58%
1/173
|
|
Nervous system disorders
Sciatica
|
2.9%
5/173
|
|
Nervous system disorders
Sinus headache
|
6.4%
11/173
|
|
Nervous system disorders
Speech disorder
|
0.58%
1/173
|
|
Nervous system disorders
Syncope
|
2.9%
5/173
|
|
Nervous system disorders
Tension headache
|
1.2%
2/173
|
|
Nervous system disorders
Tinel's sign
|
0.58%
1/173
|
|
Nervous system disorders
Transient ischaemic attack
|
1.2%
2/173
|
|
Nervous system disorders
Tremor
|
35.8%
62/173
|
|
Nervous system disorders
VIth nerve paralysis
|
0.58%
1/173
|
|
Psychiatric disorders
Abnormal dreams
|
0.58%
1/173
|
|
Psychiatric disorders
Agitation
|
1.2%
2/173
|
|
Nervous system disorders
Anxiety
|
13.3%
23/173
|
|
Psychiatric disorders
Attention deficit/hyperactivity disorder
|
0.58%
1/173
|
|
Psychiatric disorders
Bipolar disorder
|
0.58%
1/173
|
|
Psychiatric disorders
Confusional state
|
4.0%
7/173
|
|
Psychiatric disorders
Daydreaming
|
0.58%
1/173
|
|
Psychiatric disorders
Depression
|
11.6%
20/173
|
|
Psychiatric disorders
Disorientation
|
5.2%
9/173
|
|
Psychiatric disorders
Dissociation
|
0.58%
1/173
|
|
Psychiatric disorders
Emotional disorder
|
1.7%
3/173
|
|
Psychiatric disorders
Flat affect
|
0.58%
1/173
|
|
Nervous system disorders
Intentional self-injury
|
0.58%
1/173
|
|
Psychiatric disorders
Mental status changes
|
0.58%
1/173
|
|
Psychiatric disorders
Mood altered
|
0.58%
1/173
|
|
Psychiatric disorders
Nervousness
|
9.8%
17/173
|
|
Psychiatric disorders
Nightmare
|
0.58%
1/173
|
|
Psychiatric disorders
Restlessness
|
1.7%
3/173
|
|
Psychiatric disorders
Sleep disorder
|
2.3%
4/173
|
|
Psychiatric disorders
Stress
|
11.6%
20/173
|
|
Psychiatric disorders
Thinking abnormal
|
0.58%
1/173
|
|
Renal and urinary disorders
Bladder spasm
|
0.58%
1/173
|
|
Renal and urinary disorders
Dysuria
|
2.9%
5/173
|
|
Renal and urinary disorders
Haematuria
|
1.7%
3/173
|
|
Renal and urinary disorders
Hydronephrosis
|
0.58%
1/173
|
|
Renal and urinary disorders
Hypercalciuria
|
0.58%
1/173
|
|
Renal and urinary disorders
Microalbuminuria
|
4.0%
7/173
|
|
Renal and urinary disorders
Micturition disorder
|
0.58%
1/173
|
|
Renal and urinary disorders
Micturition urgency
|
1.7%
3/173
|
|
Renal and urinary disorders
Nephrolithiasis
|
4.0%
7/173
|
|
Renal and urinary disorders
Nephropathy
|
1.2%
2/173
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.58%
1/173
|
|
Renal and urinary disorders
Nocturia
|
1.2%
2/173
|
|
Renal and urinary disorders
Pollakiuria
|
2.9%
5/173
|
|
Renal and urinary disorders
Polyuria
|
2.9%
5/173
|
|
Renal and urinary disorders
Proteinuria
|
1.7%
3/173
|
|
Renal and urinary disorders
Renal cyst
|
0.58%
1/173
|
|
Renal and urinary disorders
Renal failure
|
0.58%
1/173
|
|
Renal and urinary disorders
Renal failure chronic
|
0.58%
1/173
|
|
Renal and urinary disorders
Stress urinary incontinence
|
1.2%
2/173
|
|
Renal and urinary disorders
Urinary incontinence
|
1.2%
2/173
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.58%
1/173
|
|
Renal and urinary disorders
Urine odour abnormal
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Amenorrhoea
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Atrophic vulvovaginitis
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Breast mass
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Breast pain
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Breast tenderness
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Cervical polyp
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
1.7%
3/173
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
8.1%
14/173
|
|
Reproductive system and breast disorders
Fallopian tube cyst
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Fallopian tube disorder
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Menorrhagia
|
1.7%
3/173
|
|
Reproductive system and breast disorders
Menstruation irregular
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Ovarian cyst
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Pelvic peritoneal adhesions
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Peyronie's disease
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Prostatomegaly
|
1.2%
2/173
|
|
Reproductive system and breast disorders
Testicular cyst
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Testicular pain
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Uterine haemorrhage
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Vulva cyst
|
0.58%
1/173
|
|
Reproductive system and breast disorders
Vulvovaginal pruritus
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
4.0%
7/173
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
1.2%
2/173
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial irritation
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
40.5%
70/173
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
2.3%
4/173
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
2.3%
4/173
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.2%
16/173
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
2.3%
4/173
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.3%
4/173
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Hypoventilation
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Increased upper airway secretion
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
1.7%
3/173
|
|
Respiratory, thoracic and mediastinal disorders
Mediastinal disorder
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
13.3%
23/173
|
|
Respiratory, thoracic and mediastinal disorders
Nasal disorder
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
1.2%
2/173
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
23.1%
40/173
|
|
Respiratory, thoracic and mediastinal disorders
Painful respiration
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
1.2%
2/173
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal haemorrhage
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
5.2%
9/173
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.9%
12/173
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
5.8%
10/173
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary granuloma
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Rales
|
2.3%
4/173
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
1.2%
2/173
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory gas exchange disorder
|
1.2%
2/173
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract irritation
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Rhinalgia
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
10.4%
18/173
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis seasonal
|
1.2%
2/173
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.2%
9/173
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
17.9%
31/173
|
|
Respiratory, thoracic and mediastinal disorders
Sinus polyp
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
4.0%
7/173
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
5.8%
10/173
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
|
0.58%
1/173
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
4.0%
7/173
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
4.0%
7/173
|
|
Skin and subcutaneous tissue disorders
Acrodermatitis
|
2.3%
4/173
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Blister
|
3.5%
6/173
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
3.5%
6/173
|
|
Skin and subcutaneous tissue disorders
Dandruff
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
3.5%
6/173
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
2.9%
5/173
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.0%
7/173
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Eczema
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Erythema
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Granuloma annulare
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
19.7%
34/173
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
3.5%
6/173
|
|
Skin and subcutaneous tissue disorders
Hypoaesthesia facial
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
5.2%
9/173
|
|
Skin and subcutaneous tissue disorders
Nail discomfort
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Onychogryphosis
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Onychomadesis
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Periorbital oedema
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.9%
24/173
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Rash vesicular
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Seborrhoea
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
1.7%
3/173
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
5.2%
9/173
|
|
Skin and subcutaneous tissue disorders
Skin nodule
|
1.2%
2/173
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
5.8%
10/173
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.58%
1/173
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.5%
6/173
|
|
Social circumstances
Family stress
|
1.2%
2/173
|
|
Social circumstances
Menopause
|
0.58%
1/173
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
0.58%
1/173
|
|
Surgical and medical procedures
Female sterilisation
|
0.58%
1/173
|
|
Surgical and medical procedures
Prophylaxis
|
0.58%
1/173
|
|
Surgical and medical procedures
Sebaceous cyst excision
|
0.58%
1/173
|
|
Surgical and medical procedures
Sinus operation
|
2.9%
5/173
|
|
Vascular disorders
Aneurysm
|
1.2%
2/173
|
|
Vascular disorders
Aortic stenosis
|
0.58%
1/173
|
|
Vascular disorders
Arterial thrombosis
|
0.58%
1/173
|
|
Vascular disorders
Arterial thrombosis limb
|
0.58%
1/173
|
|
Vascular disorders
Flushing
|
1.7%
3/173
|
|
Vascular disorders
Haematoma
|
2.9%
5/173
|
|
Vascular disorders
Hot flush
|
2.9%
5/173
|
|
Vascular disorders
Hypertension
|
15.6%
27/173
|
|
Vascular disorders
Intermittent claudication
|
0.58%
1/173
|
|
Vascular disorders
Pallor
|
0.58%
1/173
|
|
Vascular disorders
Peripheral vascular disorder
|
0.58%
1/173
|
|
Vascular disorders
Raynaud's phenomenon
|
1.2%
2/173
|
|
Vascular disorders
Thrombosis
|
0.58%
1/173
|
|
Vascular disorders
Vein disorder
|
0.58%
1/173
|
|
Psychiatric disorders
Insomnia
|
9.8%
17/173
|
|
Psychiatric disorders
Panic Disorder
|
0.58%
1/173
|
|
Nervous system disorders
Somnolence
|
4.0%
7/173
|
|
Nervous system disorders
Neuropathy peripheral
|
11.0%
19/173
|
|
Nervous system disorders
Sensory Disturbance
|
1.2%
2/173
|
|
Infections and infestations
Gingival abscess
|
0.58%
1/173
|
|
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy
|
0.58%
1/173
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \<60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \<12 mo from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
- Publication restrictions are in place
Restriction type: OTHER