Diabetes Mellitus
Conditions
Brief summary
This is a long-term safety study for Phase 2 subjects who choose to remain on Exubera® (inhaled insulin).
Detailed description
The study was terminated on Oct. 18, 2007. This study is not a post approval commitment study. Pfizer decided to cancel new trials because of the decision to withdraw Exubera® (inhaled insulin) due to lack of market performance and not for safety reasons.
Interventions
DRUGExubera® (inhaled insulin)
Treatment of type 1 and type 2 diabetes with short-acting insulin
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with Type 1 or Type 2 Diabetes Mellitus who participated in previous Phase 2 extension protocols
Exclusion criteria
* Smoking * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment | Baseline to 126 months | 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. |
| Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment | baseline to 126 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | 0-132 months | 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. |
| Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 36 months to 126 months | Observed values by duration of treatment. |
| Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry) | 36 to 126 months | observed values by duration of treatment. |
| Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | Baseline to 126 months | 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. |
| 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 to >=108 months | Decliners = decline of ≥15% in forced expiratory volume or ≥20% in carbon monoxide diffusing capacity. |
| Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 3 to >=108 months | Decliners at particular timepoint were defined as any decline of ≥15% in forced expiratory volume. |
| Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 6 to >=108 months | Decliners at particular timepoint were defined as any decline of ≥20% in carbon monoxide diffusing capacity. |
| Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry) | 6 to 120 months | Observed values by duration of treatment. |
| Hypoglycemic Event Rates by Interval of Exubera Treatment | 0 to 132 months | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 173 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 19 |
| Overall Study | Death | 8 |
| Overall Study | following inaccurate lab adverse event | 1 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 12 |
| Overall Study | Other | 12 |
| Overall Study | Protocol Violation | 15 |
| Overall Study | Study terminated by sponsor | 31 |
| Overall Study | Withdrawal by Subject | 55 |
Baseline characteristics
| Characteristic | Inhaled Insulin |
|---|---|
| Age Continuous | 46.6 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 172 / — |
| serious Total, serious adverse events | 63 / — |
Outcome results
Primary
Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment
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.
Time frame: baseline to 126 months
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 4.69 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 5.03 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
Primary
Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment
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.
Time frame: Baseline to 126 months
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment | 12 months (n=138) | -0.137 liters | Standard Deviation 0.22 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment | 54 months (n=83) | -0.291 liters | Standard Deviation 0.26 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
Secondary
Change in Glycosylated Hemoglobin by Duration of Exubera Treatment
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.
Time frame: Baseline to 126 months
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 3 months (n=155) | -0.99 percent HbA1C | Standard Deviation 1.37 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 6 months (n=146) | -0.90 percent HbA1C | Standard Deviation 1.58 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 12 months (n=136) | -0.60 percent HbA1C | Standard Deviation 1.72 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 18 months (n=121) | -0.66 percent HbA1C | Standard Deviation 1.61 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 24 months (n=115) | -0.65 percent HbA1C | Standard Deviation 1.67 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 30 months (n=107) | -0.67 percent HbA1C | Standard Deviation 1.72 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 36 months (n=99) | -0.60 percent HbA1C | Standard Deviation 1.73 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 42 months (n=93) | -0.61 percent HbA1C | Standard Deviation 1.72 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 48 months (n=88) | -0.48 percent HbA1C | Standard Deviation 1.64 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 54 months (n=83) | -0.50 percent HbA1C | Standard Deviation 1.61 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 60 months (n=75) | -0.48 percent HbA1C | Standard Deviation 1.56 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 66 months (n=70) | -0.56 percent HbA1C | Standard Deviation 1.82 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 72 months (n=67) | -0.61 percent HbA1C | Standard Deviation 1.87 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 78 months (n=62) | -0.80 percent HbA1C | Standard Deviation 1.47 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 84 months (n=57) | -0.71 percent HbA1C | Standard Deviation 1.26 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 90 months (n=56) | -0.75 percent HbA1C | Standard Deviation 1.51 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 96 months (n=54) | -0.58 percent HbA1C | Standard Deviation 1.46 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 102 months (n=50) | -0.77 percent HbA1C | Standard Deviation 1.52 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 108 months (n=42) | -0.68 percent HbA1C | Standard Deviation 1.51 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 114 months (n=37) | -0.78 percent HbA1C | Standard Deviation 1.6 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 120 months (n=31) | -0.39 percent HbA1C | Standard Deviation 1.46 |
| Inhaled Insulin | Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | 126 months (n=23) | -0.08 percent HbA1C | Standard Deviation 1.22 |
Secondary
Hypoglycemic Event Rates by Interval of Exubera Treatment
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.
Time frame: 0 to 132 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | 0 to 4 weeks (n=159) | 2.38 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >4 to 8 weeks (n=158) | 2.10 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >36 to 42 months (n=98) | 1.54 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >96 to 102 months (n=52) | 1.52 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >8 to 12 weeks (n=157) | 1.92 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >12 weeks to 6 months (n=155) | 1.88 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >6 to12 months (n=149) | 1.91 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >12 to18 months (n=134) | 1.63 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >18 to 24 months (n=122) | 1.96 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >24 to 30 months (n=112) | 1.99 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >30 to 36 months (n=107) | 1.78 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >42 to 48 months (n=91) | 1.47 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >48 to 54 months (n=85) | 1.36 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >54 to 60 months (n=80) | 1.38 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >60 to 66 months (n=74) | 1.32 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >66 to 72 months (n=70) | 1.42 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >72 to 78 months (n=64) | 1.47 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >78 to 84 months (n=59) | 1.74 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >84 to 90 months (n=58) | 1.63 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >90 to 96 months (n=56) | 1.67 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >102 to 108 months (n=48) | 1.16 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >108 to 114 months (n=40) | 1.51 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >114 to 120 months (n=37) | 1.41 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >120 to 126 months (n=25) | 1.13 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | >126 to 132 months (n=18) | 0.92 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates by Interval of Exubera Treatment | Overall (n=159) | 1.65 events / subject-month |
Secondary
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes
Observed values by duration of treatment.
Time frame: 36 months to 126 months
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 48 months (n=28) | 19.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 54 months (n=27) | 16.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 60 months (n=26) | 14.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 66 months (n=23) | 16.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 72 months (n=22) | 13.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 78 months (n=24) | 14.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 84 months (n=23) | 16.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 90 months (n=21) | 13.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 96 months (n=23) | 18.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 102 months (n=21) | 14.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 108 months (n=17) | 18.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 114 months (n=15) | 11.00 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 120 months (n=14) | 8.50 percent binding | — |
| Inhaled Insulin | Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | 126 months (n=14) | 9.00 percent binding | — |
Secondary
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry)
Observed values by duration of treatment.
Time frame: 6 to 120 months
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
Secondary
Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry)
observed values by duration of treatment.
Time frame: 36 to 126 months
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
| Inhaled Insulin | 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 | — |
Secondary
Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment
Decliners at particular timepoint were defined as any decline of ≥20% in carbon monoxide diffusing capacity.
Time frame: 6 to >=108 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 6 months (n=149) | 16 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 12 months (n=130) | 8 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 18 months (n=115) | 13 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 24 months (n=113) | 21 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 30 months (n=100) | 14 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 36 months (n=95) | 14 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 42 months (n=86) | 13 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 48 months (n=82) | 11 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 54 months (n=80) | 11 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 60 months (n=70) | 10 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 66 months (n=64) | 11 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 72 months (n=62) | 8 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 78 months (n=59) | 11 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 84 months (n=57) | 10 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 90 months (n=50) | 5 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 96 months (n=52) | 4 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | 102 months (n=42) | 4 participants |
| Inhaled Insulin | Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | >=108 months (n=41) | 13 participants |
Secondary
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
Decliners = decline of ≥15% in forced expiratory volume or ≥20% in carbon monoxide diffusing capacity.
Time frame: 3 to >=108 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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
Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment
Decliners at particular timepoint were defined as any decline of ≥15% in forced expiratory volume.
Time frame: 3 to >=108 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 3 months (n=154) | 2 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 6 months (n=149) | 5 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 12 months (n=138) | 6 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 18 months (n=123) | 5 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 24 months (n=116) | 9 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 30 months (n=108) | 14 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 36 months (n=101) | 18 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 42 months (n=92) | 18 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 48 months (n=88) | 19 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 54 months (n=83) | 14 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 60 months (n=75) | 21 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 66 months (n=70) | 19 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 72 months (n=67) | 17 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 78 months (n=61) | 17 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 84 months (n=57) | 21 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 90 months (n=56) | 24 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 96 months (n=54) | 19 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | 102 months (n=50) | 24 participants |
| Inhaled Insulin | Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | >=108 months (n=42) | 27 participants |
Secondary
Severe Hypoglycemic Event Rates by Interval of Exubera Treatment
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.
Time frame: 0-132 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >6-12 months (n=149) | 1.07 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >24-30 months (n=112) | 1.07 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | Overall (n=159) | 0.88 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | 0-4 weeks (n=159) | 1.37 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >4-8 weeks (n=158) | 2.76 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >8-12 weeks (n=157) | 0.70 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >12 weeks-6months (n=155) | 2.64 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >12-18 months (n=134) | 0.93 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >18-24 months (n=122) | 0.85 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >30-36 months (n=107) | 0.97 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >36-42 months (n=98) | 0.18 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >42-48 months (n=91) | 0.19 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >48-54 months (n=85) | 0.60 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >54-60 months (n=80) | 0.87 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >60-66 months (n=74) | 0.47 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >66-72 months (n=70) | 0.75 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >72-78 months (n=64) | 0.27 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >78-84 months (n=59) | 1.14 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >84-90 months (n=58) | 1.47 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >90-96 months (n=56) | 0.31 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >96-102 months (n=52) | 1.32 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >102-108 months (n=48) | 0.39 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >108-114 months (n=40) | 0.44 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >114-120 months (n=37) | 0.54 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >120-126 months (n=25) | 0 severe events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | >126-132 months (n=18) | 0 severe events / 100 subject-months |