Trial Outcomes & Findings for A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With COPD (NCT NCT00138671)
NCT ID: NCT00138671
Last Updated: 2010-02-02
Results Overview
FEV1 was measured in liters (L) 30 minutes following the administration of ipratropium. Change from baseline: mean of (value of observed FEV1 (L) at treatment duration minus baseline value).
TERMINATED
PHASE3
105 participants
Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52
2010-02-02
Participant Flow
Participant milestones
| Measure |
Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Overall Study
STARTED
|
59
|
46
|
|
Overall Study
COMPLETED
|
46
|
30
|
|
Overall Study
NOT COMPLETED
|
13
|
16
|
Reasons for withdrawal
| Measure |
Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Overall Study
Death
|
0
|
3
|
|
Overall Study
Adverse Event
|
6
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
5
|
|
Overall Study
Other
|
3
|
3
|
Baseline Characteristics
A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With COPD
Baseline characteristics by cohort
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=46 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
36 to 45 years
|
1 participants
n=93 Participants
|
3 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
Age, Customized
46 to 55 years
|
10 participants
n=93 Participants
|
4 participants
n=4 Participants
|
14 participants
n=27 Participants
|
|
Age, Customized
56 to 65 years
|
20 participants
n=93 Participants
|
23 participants
n=4 Participants
|
43 participants
n=27 Participants
|
|
Age, Customized
66 to 75 years
|
27 participants
n=93 Participants
|
15 participants
n=4 Participants
|
42 participants
n=27 Participants
|
|
Age, Customized
> 75 years
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=93 Participants
|
37 Participants
n=4 Participants
|
79 Participants
n=27 Participants
|
|
Primary Diagnosis (Diabetes Type I or II)
Type I
|
7 participants
n=93 Participants
|
6 participants
n=4 Participants
|
13 participants
n=27 Participants
|
|
Primary Diagnosis (Diabetes Type I or II)
Type II
|
52 participants
n=93 Participants
|
40 participants
n=4 Participants
|
92 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52Population: Full Analysis Set (FAS), FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had at least 1 FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
FEV1 was measured in liters (L) 30 minutes following the administration of ipratropium. Change from baseline: mean of (value of observed FEV1 (L) at treatment duration minus baseline value).
Outcome measures
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 2 (n=51, 40)
|
-0.039 L
Standard Deviation 0.116
|
-0.042 L
Standard Deviation 0.120
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 3 (n=47, 40)
|
-0.026 L
Standard Deviation 0.121
|
-0.048 L
Standard Deviation 0.145
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 4 (n=50, 38)
|
-0.050 L
Standard Deviation 0.140
|
-0.039 L
Standard Deviation 0.151
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 12 (n=48, 41)
|
-0.056 L
Standard Deviation 0.180
|
-0.007 L
Standard Deviation 0.187
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 18 (n=52, 37)
|
-0.049 L
Standard Deviation 0.158
|
-0.071 L
Standard Deviation 0.195
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 39, (n=47, 34)
|
-0.053 L
Standard Deviation 0.174
|
-0.092 L
Standard Deviation 0.232
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 52 (n=45, 30)
|
-0.068 L
Standard Deviation 0.208
|
-0.128 L
Standard Deviation 0.184
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 1 (n=52, 39)
|
-0.021 L
Standard Deviation 0.132
|
-0.018 L
Standard Deviation 0.125
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 6 (n=53, 38)
|
-0.045 L
Standard Deviation 0.152
|
-0.070 L
Standard Deviation 0.165
|
|
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Week 26 (n=52, 38)
|
-0.067 L
Standard Deviation 0.174
|
-0.096 L
Standard Deviation 0.189
|
PRIMARY outcome
Timeframe: Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52Population: FAS, FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had at least 1 FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
DLco measured in milliters/minutes/millimeters of mercury (mL/min/mmHg) 30 minutes following the administration of ipratropium. Change from baseline: mean of (value of observed DLco (mL/min/mmHg) at treatment duration minus baseline value).
Outcome measures
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 39 (n=47, 33)
|
-0.611 mL/min/mmHg
Standard Deviation 1.475
|
-0.891 mL/min/mmHg
Standard Deviation 2.137
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 52 (n=45, 29)
|
-0.614 mL/min/mmHg
Standard Deviation 1.754
|
-0.882 mL/min/mmHg
Standard Deviation 1.720
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 1 (n=51, 40)
|
-0.263 mL/min/mmHg
Standard Deviation 1.610
|
-0.319 mL/min/mmHg
Standard Deviation 0.984
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 2 (n=51, 40)
|
-0.491 mL/min/mmHg
Standard Deviation 1.288
|
-0.031 mL/min/mmHg
Standard Deviation 1.106
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 3 (n=47, 40)
|
-0.494 mL/min/mmHg
Standard Deviation 1.175
|
0.169 mL/min/mmHg
Standard Deviation 1.303
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 4 (n=50, 39)
|
-0.640 mL/min/mmHg
Standard Deviation 1.345
|
-0.482 mL/min/mmHg
Standard Deviation 1.321
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 6 (n=52, 38)
|
-0.625 mL/min/mmHg
Standard Deviation 1.356
|
-0.576 mL/min/mmHg
Standard Deviation 1.226
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 12 (n=47, 40)
|
-0.379 mL/min/mmHg
Standard Deviation 1.516
|
-0.534 mL/min/mmHg
Standard Deviation 1.506
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 18 (n=51, 36)
|
-0.287 mL/min/mmHg
Standard Deviation 1.463
|
-0.286 mL/min/mmHg
Standard Deviation 1.796
|
|
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
Week 26 (n=52, 38)
|
-0.287 mL/min/mmHg
Standard Deviation 1.841
|
-0.947 mL/min/mmHg
Standard Deviation 1.643
|
SECONDARY outcome
Timeframe: Duration of the studyFull PFTs included spirometry pre- and 30-minutes post-ipratropium and were completed between the hours of 6 AM and 10 AM with subjects in the fasting state. Full PFT data were collected, but not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Duration of the studyFull PFTs included DLco pre- and 30-minutes post-ipratropium and were completed between the hours of 6 AM and 10 AM with subjects in the fasting state. Full PFT data were collected, but not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Duration of the studyOther PFTs (besides FEV1 and DLco) were measured 30 minutes following the administration of ipratropium. Other PFTs included forced vital capacity (FVC), peak expiratory flow rate (maximal forced expiratory flow) (PEFR\[FEFmax\]), and forced expiratory flow from 25% to 75% of vital capacity (FEF25%-75%). Other PFT data were collected, but not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52Population: FAS, FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had at least 1 FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Responsiveness was the percent change from the FEV1 value before bronchodilator use to the FEV1 value 30 minutes after bronchodilator use, operationally defined as \[(post-bronchodilator FEV1 minus pre-bronchodilator FEV1 divided by pre-bronchodilator FEV1\] multiplied by 100.
Outcome measures
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 1 (n=52, 39)
|
4.890 percent change
Standard Deviation 5.727
|
5.693 percent change
Standard Deviation 7.249
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 2 (n=51, 40)
|
6.132 percent change
Standard Deviation 6.200
|
5.245 percent change
Standard Deviation 6.254
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 3 (n=47, 40)
|
6.346 percent change
Standard Deviation 7.469
|
5.820 percent change
Standard Deviation 8.347
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 4 (n=50, 38)
|
5.177 percent change
Standard Deviation 7.211
|
6.382 percent change
Standard Deviation 9.685
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 18 (n=52, 37)
|
6.700 percent change
Standard Deviation 6.020
|
5.152 percent change
Standard Deviation 8.155
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 26 (n=52, 38)
|
5.585 percent change
Standard Deviation 5.592
|
5.856 percent change
Standard Deviation 8.562
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 39 (n=47, 34)
|
6.634 percent change
Standard Deviation 5.829
|
6.098 percent change
Standard Deviation 9.311
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 52 (n=45, 30)
|
6.030 percent change
Standard Deviation 4.700
|
5.445 percent change
Standard Deviation 8.390
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 6 (n=53, 38)
|
5.988 percent change
Standard Deviation 6.034
|
7.736 percent change
Standard Deviation 10.139
|
|
Bronchodilator Responsiveness as Determined by the Change in FEV1
Week 12 (n=48, 41)
|
6.473 percent change
Standard Deviation 8.994
|
5.542 percent change
Standard Deviation 6.791
|
SECONDARY outcome
Timeframe: Baseline, Week 9, Week 51Population: FAS, FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had at least 1 FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
FEV1 dose responsiveness 10 and 60 minutes after insulin. FEV1 dose-responsiveness to insulin (defined as the difference between the FEV1 value following a dose of insulin and FEV1 value before a dose of insulin, operationally defined as the post-dose FEV1 value minus pre-dose FEV1 value).
Outcome measures
| Measure |
Inhaled Insulin
n=50 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=39 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Insulin Dose Responsiveness for FEV1
Baseline, 10 minutes (n=50, 39)
|
0.009 L
Standard Deviation 0.076
|
0.022 L
Standard Deviation 0.106
|
|
Insulin Dose Responsiveness for FEV1
Week 9, 10 minutes (n=42, 31)
|
-0.004 L
Standard Deviation 0.110
|
0.016 L
Standard Deviation 0.096
|
|
Insulin Dose Responsiveness for FEV1
Week 9, 60 minutes (n=42, 30)
|
0.011 L
Standard Deviation 0.109
|
0.030 L
Standard Deviation 0.116
|
|
Insulin Dose Responsiveness for FEV1
Week 51, 10 minutes (n=46, 31)
|
-0.021 L
Standard Deviation 0.121
|
-0.002 L
Standard Deviation 0.084
|
|
Insulin Dose Responsiveness for FEV1
Baseline, 60 minutes (n=50, 39)
|
-0.004 L
Standard Deviation 0.096
|
0.020 L
Standard Deviation 0.127
|
|
Insulin Dose Responsiveness for FEV1
Week 51, 60 minutes (n=45, 31)
|
0.005 L
Standard Deviation 0.115
|
-0.020 L
Standard Deviation 0.141
|
SECONDARY outcome
Timeframe: Baseline, Week 9, Week 51Population: FAS, FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had a FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
DLco dose responsivness 10 and 60 minutes after insulin. DLco dose-responsiveness to insulin (defined as the difference between the DLco value following a dose of insulin and DLco value before a dose of insulin, operationally defined as the post-dose DLco value minus pre-dose DLco value).
Outcome measures
| Measure |
Inhaled Insulin
n=48 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=39 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Insulin Dose Responsiveness for DLco
Week 9, 10 minutes (n=41, 30)
|
-0.182 mL/min/mmHg
Standard Deviation 1.015
|
-0.238 mL/min/mmHg
Standard Deviation 1.505
|
|
Insulin Dose Responsiveness for DLco
Week 51, 10 minutes (n=44, 31)
|
-0.465 mL/min/mmHg
Standard Deviation 0.781
|
0.054 mL/min/mmHg
Standard Deviation 1.204
|
|
Insulin Dose Responsiveness for DLco
Baseline, 10 minutes (n=48, 39)
|
-0.461 mL/min/mmHg
Standard Deviation 1.157
|
-0.195 mL/min/mmHg
Standard Deviation 0.707
|
|
Insulin Dose Responsiveness for DLco
Baseline, 60 minutes (n=49, 39)
|
-0.597 mL/min/mmHg
Standard Deviation 1.102
|
-0.160 mL/min/mmHg
Standard Deviation 1.217
|
|
Insulin Dose Responsiveness for DLco
Week 9, 60 minutes (n=42, 29)
|
0.013 mL/min/mmHg
Standard Deviation 2.288
|
-0.373 mL/min/mmHg
Standard Deviation 1.574
|
|
Insulin Dose Responsiveness for DLco
Week 51, 60 minutes (n=44, 31)
|
-0.395 mL/min/mmHg
Standard Deviation 0.885
|
-0.163 mL/min/mmHg
Standard Deviation 1.211
|
SECONDARY outcome
Timeframe: Duration of the studyMethacholine challenge testing was conducted at selected sites at visits which did not occur at other sites (Weeks -2.9, -0.9, 11, 50 and 52+5). Methacholine challenge was not analyzed as there was only 1 test performed, which was a baseline test, and no methacholine tests performed in subjects using inhaled insulin.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Duration of the studyAll subjects used diary cards to record their daily use of short-acting bronchodilators. Subjects recorded the sum of their short-acting bronchodilator use (puffs of albuterol plus ipratropium plus Combivent®, as applicable) daily, immediately upon arising, and again in the evening or before bed. Mean weekly number of puffs of short-acting bronchodilator used data were collected, but not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 0 to 1 week to > 9 monthsPopulation: FAS, FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had at least 1 FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Non-severe COPD exacerbation = additional therapy (systemic corticosteroids, antibiotics, oxygen) needed for worsening respiratory symptoms and/or lung function, not needing hospitalization \> 24 hours. Crude event rate = total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.
Outcome measures
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 2 to 3 weeks (n=59, 43)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 3 to 4 weeks (n=59, 42)
|
0.07 events/subject-month (crude event rate)
|
0.10 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 4 to 6 weeks (n=57, 42)
|
0.08 events/subject-month (crude event rate)
|
0.05 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 6 to 9 weeks (n=56, 42)
|
0.05 events/subject-month (crude event rate)
|
0.03 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 9 to 12 weeks (n=55, 41)
|
0.05 events/subject-month (crude event rate)
|
0.07 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 3 to 6 months (n=52, 41)
|
0.02 events/subject-month (crude event rate)
|
0.01 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 6 to 9 months (n=52, 37)
|
0.01 events/subject-month (crude event rate)
|
0.01 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 9 months (n=50, 35)
|
0.01 events/subject-month (crude event rate)
|
0.02 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
Overall (n=59, 43)
|
0.02 events/subject-month (crude event rate)
|
0.02 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
0 to 1 week (n=59, 43)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
> 1 to 2 weeks (n=59, 43)
|
0.07 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
SECONDARY outcome
Timeframe: 0 to 1 week to > 9 monthsPopulation: FAS, FEV1=all randomized subjects who received at least 1 dose of study treatment, had a baseline FEV1 measurement (post-bronchodilator), and had at least 1 FEV1 post-baseline measurement (post-bronchodilator). Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Severe COPD exacerbation = a COPD-related hospitalization \> 24 hours. Crude event rate = total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.
Outcome measures
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Incidence of Severe COPD Exacerbations
> 2 to 3 weeks (n=59, 43)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 3 to 4 weeks (n=59, 42)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 6 to 9 weeks (n=56, 42)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 9 to 12 weeks (n=55, 41)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
0 to 1 week (n=59, 43)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 1 to 2 weeks (n=59, 43)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 4 to 6 weeks (n=57, 42)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 3 to 6 months (n=52, 41)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 6 to 9 months (n=52, 37)
|
0.01 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
> 9 months (n=50, 35)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
|
Incidence of Severe COPD Exacerbations
Overall (n= 59, 43)
|
0.00 events/subject-month (crude event rate)
|
0.00 events/subject-month (crude event rate)
|
SECONDARY outcome
Timeframe: Duration of the studyThe BDI and TDI measured or quantitated the severity of breathlessness (shortness of breath) in symptomatic subjects. BDI and TDI data were collected, but not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Weeks 6, 12, 26, 39, and 52Population: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Week 52 Last Observation Carried Forward (LOCF)=subjects' last measurement carried forward. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Change from baseline: mean of (value of observed HbA1c at treatment duration minus baseline value).
Outcome measures
| Measure |
Inhaled Insulin
n=57 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Week 39 (n=48, 35)
|
-0.34 percent
Standard Deviation 1.11
|
-0.20 percent
Standard Deviation 1.01
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Week 52 (n=46, 32)
|
-0.30 percent
Standard Deviation 1.10
|
-0.23 percent
Standard Deviation 0.84
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Week 6 (n=56, 40)
|
-0.40 percent
Standard Deviation 0.81
|
-0.48 percent
Standard Deviation 0.60
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Week 12 (n=50, 41)
|
-0.53 percent
Standard Deviation 0.98
|
-0.42 percent
Standard Deviation 0.65
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Week 26 (n=52, 38)
|
-0.39 percent
Standard Deviation 0.96
|
-0.32 percent
Standard Deviation 0.79
|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Week 52 LOCF (n=57, 43)
|
-0.28 percent
Standard Deviation 1.03
|
-0.26 percent
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: Baseline, Weeks 6, 12, 26, 39, 52Population: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Week 52 Last Observation Carried Forward (LOCF)=subjects' last measurement carried forward. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Change from baseline: mean of (value of observed fasting plasma glucose in milligrams/deciliters (mg/dL) at treatment duration minus baseline value).
Outcome measures
| Measure |
Inhaled Insulin
n=57 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose
Week 39 (n=47, 33)
|
-20.45 mg/dL
Standard Deviation 56.62
|
10.43 mg/dL
Standard Deviation 98.53
|
|
Change From Baseline in Fasting Plasma Glucose
Week 52 (n=45, 31)
|
-23.40 mg/dL
Standard Deviation 65.77
|
12.37 mg/dL
Standard Deviation 58.01
|
|
Change From Baseline in Fasting Plasma Glucose
Week 6 (n=52, 39)
|
-24.67 mg/dL
Standard Deviation 69.69
|
2.89 mg/dL
Standard Deviation 41.17
|
|
Change From Baseline in Fasting Plasma Glucose
Week 12 (n=48, 39)
|
-30.73 mg/dL
Standard Deviation 52.99
|
-0.18 mg/dL
Standard Deviation 46.25
|
|
Change From Baseline in Fasting Plasma Glucose
Week 26 (n=47, 38)
|
-34.92 mg/dL
Standard Deviation 61.63
|
10.45 mg/dL
Standard Deviation 62.80
|
|
Change From Baseline in Fasting Plasma Glucose
Week 52 (LOCF) (n=57, 43)
|
-28.55 mg/dL
Standard Deviation 65.85
|
2.36 mg/dL
Standard Deviation 66.51
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 3, 4, 6, 9, 11, 12, 18, 26, 39, 50, 51, 52Population: FAS, HbA1c=randomized subjects with \>=1 study drug dose, baseline and \>=1 post-baseline HbA1c measurement. Last Observation Carried Forward (LOCF) method used. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin. Week 11 and 50 visits were part of the methacholine substudy and were not required visits for all subjects.
Change from baseline: mean of (value of observed body weight in kilograms (kg) at treatment duration minus baseline value).
Outcome measures
| Measure |
Inhaled Insulin
n=59 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Change From Baseline in Body Weight
Week 1 (n=52, 40)
|
0.25 kg
Standard Deviation 1.62
|
0.02 kg
Standard Deviation 0.98
|
|
Change From Baseline in Body Weight
Week 3 (n=49, 41)
|
0.19 kg
Standard Deviation 2.03
|
0.13 kg
Standard Deviation 1.90
|
|
Change From Baseline in Body Weight
Week 4 (n=53, 41)
|
0.19 kg
Standard Deviation 1.98
|
0.24 kg
Standard Deviation 2.13
|
|
Change From Baseline in Body Weight
Week 6 (n=54, 39)
|
0.42 kg
Standard Deviation 2.26
|
0.26 kg
Standard Deviation 1.94
|
|
Change From Baseline in Body Weight
Week 18 (n=52, 37)
|
0.40 kg
Standard Deviation 3.66
|
0.90 kg
Standard Deviation 4.01
|
|
Change From Baseline in Body Weight
Week 52 (n=43, 27)
|
0.97 kg
Standard Deviation 5.65
|
3.32 kg
Standard Deviation 4.68
|
|
Change From Baseline in Body Weight
Week 52 LOCF (n=59, 43)
|
0.99 kg
Standard Deviation 4.20
|
2.40 kg
Standard Deviation 4.79
|
|
Change From Baseline in Body Weight
Week 2 (n=51, 40)
|
0.26 kg
Standard Deviation 1.77
|
0.15 kg
Standard Deviation 1.73
|
|
Change From Baseline in Body Weight
Week 9 (n=47, 34)
|
0.31 kg
Standard Deviation 2.93
|
0.25 kg
Standard Deviation 2.31
|
|
Change From Baseline in Body Weight
Week 11 (n=8, 8)
|
0.03 kg
Standard Deviation 2.25
|
-0.14 kg
Standard Deviation 2.97
|
|
Change From Baseline in Body Weight
Week 12 (n=49, 41)
|
0.42 kg
Standard Deviation 3.29
|
0.34 kg
Standard Deviation 3.69
|
|
Change From Baseline in Body Weight
Week 26 (n=52, 38)
|
0.85 kg
Standard Deviation 3.95
|
1.99 kg
Standard Deviation 4.03
|
|
Change From Baseline in Body Weight
Week 39 (n=47, 34)
|
0.61 kg
Standard Deviation 4.37
|
2.43 kg
Standard Deviation 5.21
|
|
Change From Baseline in Body Weight
Week 50 (n=8, 6)
|
1.75 kg
Standard Deviation 4.90
|
6.33 kg
Standard Deviation 9.06
|
|
Change From Baseline in Body Weight
Week 51 (n=23, 17)
|
1.21 kg
Standard Deviation 4.82
|
2.67 kg
Standard Deviation 3.28
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52Population: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Intermediate-/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups.
Outcome measures
| Measure |
Inhaled Insulin
n=51 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 1 (n=53, 40)
|
43.78 Units
Standard Deviation 22.20
|
48.18 Units
Standard Deviation 23.44
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 18 (n=51, 40)
|
50.87 Units
Standard Deviation 29.32
|
53.83 Units
Standard Deviation 29.34
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 2 (n=50, 41)
|
44.96 Units
Standard Deviation 22.50
|
48.04 Units
Standard Deviation 24.33
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 3 (n=51, 39)
|
47.04 Units
Standard Deviation 24.36
|
50.53 Units
Standard Deviation 24.44
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 4 (n=52, 41)
|
47.50 Units
Standard Deviation 25.94
|
50.30 Units
Standard Deviation 25.61
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 6 (n=54, 40)
|
49.56 Units
Standard Deviation 26.61
|
51.34 Units
Standard Deviation 25.91
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 9 (n=47, 35)
|
48.68 Units
Standard Deviation 28.61
|
56.72 Units
Standard Deviation 25.89
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 12 (n=51, 41)
|
49.23 Units
Standard Deviation 28.46
|
52.32 Units
Standard Deviation 29.49
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 26 (n=51, 38)
|
50.47 Units
Standard Deviation 28.83
|
55.78 Units
Standard Deviation 28.11
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 39 (n=49, 35)
|
49.99 Units
Standard Deviation 29.00
|
53.10 Units
Standard Deviation 26.11
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Week 52 (n=48, 34)
|
50.66 Units
Standard Deviation 30.63
|
53.39 Units
Standard Deviation 26.32
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52Population: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin.
Outcome measures
| Measure |
Inhaled Insulin
n=56 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=41 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 1 (n=54, 40)
|
12.34 mg, Units
Standard Deviation 5.26
|
32.74 mg, Units
Standard Deviation 21.59
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 2 (n=51, 41)
|
13.03 mg, Units
Standard Deviation 6.63
|
32.08 mg, Units
Standard Deviation 22.25
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 3 (n=52, 39)
|
14.10 mg, Units
Standard Deviation 6.89
|
32.88 mg, Units
Standard Deviation 21.60
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 4 (n=53, 41)
|
14.17 mg, Units
Standard Deviation 7.28
|
31.85 mg, Units
Standard Deviation 22.29
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 6 (n=55, 40)
|
15.17 mg, Units
Standard Deviation 7.20
|
33.42 mg, Units
Standard Deviation 22.72
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 9 (n=48, 35)
|
15.82 mg, Units
Standard Deviation 7.41
|
36.65 mg, Units
Standard Deviation 22.94
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 12 (n=52, 41)
|
15.64 mg, Units
Standard Deviation 7.80
|
33.58 mg, Units
Standard Deviation 23.94
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 18 (n=52, 40)
|
16.47 mg, Units
Standard Deviation 7.48
|
35.36 mg, Units
Standard Deviation 26.06
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 26 (n=52, 38)
|
16.71 mg, Units
Standard Deviation 8.05
|
37.73 mg, Units
Standard Deviation 26.14
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 39 (n=49, 35)
|
17.22 mg, Units
Standard Deviation 8.60
|
37.47 mg, Units
Standard Deviation 26.20
|
|
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Week 52 (n=48, 34)
|
16.85 mg, Units
Standard Deviation 9.52
|
39.28 mg, Units
Standard Deviation 25.13
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52Population: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Intermediate/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Dose was adjusted for body weight (units divided by kg).
Outcome measures
| Measure |
Inhaled Insulin
n=51 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 3 (n=49, 39)
|
0.50 Units/kg
Standard Deviation 0.25
|
0.50 Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 4 (n=50, 41)
|
0.49 Units/kg
Standard Deviation 0.26
|
0.50 Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 39 (n=47, 34)
|
0.51 Units/kg
Standard Deviation 0.27
|
0.54 Units/kg
Standard Deviation 0.24
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 52, (n=43, 27)
|
0.52 Units/kg
Standard Deviation 0.29
|
0.56 Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 1 (n=51, 40)
|
0.46 Units/kg
Standard Deviation 0.22
|
0.48 Units/kg
Standard Deviation 0.19
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 2 (n=50, 40)
|
0.47 Units/kg
Standard Deviation 0.22
|
0.48 Units/kg
Standard Deviation 0.20
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 6 (n=53, 39)
|
0.52 Units/kg
Standard Deviation 0.27
|
0.51 Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 9 (n=46, 34)
|
0.50 Units/kg
Standard Deviation 0.29
|
0.57 Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 12 (n=49, 41)
|
0.51 Units/kg
Standard Deviation 0.28
|
0.52 Units/kg
Standard Deviation 0.24
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 18 (n=51, 37)
|
0.53 Units/kg
Standard Deviation 0.29
|
0.55 Units/kg
Standard Deviation 0.24
|
|
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Week 26 (n=51, 38)
|
0.52 Units/kg
Standard Deviation 0.28
|
0.55 Units/kg
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52Population: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin. Dose was adjusted for body weight (mg divided by kg or units divided by kg).
Outcome measures
| Measure |
Inhaled Insulin
n=56 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=41 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 1 (n=52, 40)
|
0.13 mg/kg, Units/kg
Standard Deviation 0.05
|
0.33 mg/kg, Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 2 (n=51, 40)
|
0.14 mg/kg, Units/kg
Standard Deviation 0.06
|
0.33 mg/kg, Units/kg
Standard Deviation 0.21
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 9 (n=47, 34)
|
0.17 mg/kg, Units/kg
Standard Deviation 0.07
|
0.36 mg/kg, Units/kg
Standard Deviation 0.22
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 39 (n=47, 34)
|
0.18 mg/kg, Units/kg
Standard Deviation 0.08
|
0.38 mg/kg, Units/kg
Standard Deviation 0.25
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 3 (n=49, 39)
|
0.15 mg/kg, Units/kg
Standard Deviation 0.07
|
0.33 mg/kg, Units/kg
Standard Deviation 0.22
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 4 (n=51, 41)
|
0.15 mg/kg, Units/kg
Standard Deviation 0.07
|
0.32 mg/kg, Units/kg
Standard Deviation 0.22
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 6 (n=54, 39)
|
0.16 mg/kg, Units/kg
Standard Deviation 0.07
|
0.34 mg/kg, Units/kg
Standard Deviation 0.22
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 12 (n=49, 41)
|
0.17 mg/kg, Units/kg
Standard Deviation 0.08
|
0.34 mg/kg, Units/kg
Standard Deviation 0.23
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 18 (n=52, 37)
|
0.17 mg/kg, Units/kg
Standard Deviation 0.08
|
0.37 mg/kg, Units/kg
Standard Deviation 0.24
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 26 (n=52, 38)
|
0.18 mg/kg, Units/kg
Standard Deviation 0.08
|
0.38 mg/kg, Units/kg
Standard Deviation 0.24
|
|
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
Week 52 (n=43, 27)
|
0.18 mg/kg, Units/kg
Standard Deviation 0.09
|
0.40 mg/kg, Units/kg
Standard Deviation 0.25
|
SECONDARY outcome
Timeframe: Duration of the studyLipids collected: Total cholesterol, high-density lipoprotein, low-density lipoptrotein, and triglycerides. Lipids data were collected, but not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 0 to1 month to > 11 monthsPopulation: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
A hypoglycemic event was identified by characteristic symptoms; blood glucose levels at 59 mg/dL (3.2 mmol/L) or less with a glucose check; or any glucose measurement 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Crude event rate=total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.
Outcome measures
| Measure |
Inhaled Insulin
n=57 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Hypoglycemic Event Rates
> 6 to 7 months (n=52, 37)
|
0.62 events / subject-month
|
0.92 events / subject-month
|
|
Hypoglycemic Event Rates
> 7 to 8 months (n=51, 36)
|
0.67 events / subject-month
|
0.75 events / subject-month
|
|
Hypoglycemic Event Rates
> 11 months (n=47, 33)
|
0.62 events / subject-month
|
0.26 events / subject-month
|
|
Hypoglycemic Event Rates
Overall (n=57, 43)
|
0.89 events / subject-month
|
0.84 events / subject-month
|
|
Hypoglycemic Event Rates
0 to 1 month (n=57, 43)
|
1.76 events / subject-month
|
1.36 events / subject-month
|
|
Hypoglycemic Event Rates
> 1 to 2 months (n=56, 42)
|
1.25 events / subject-month
|
0.98 events / subject-month
|
|
Hypoglycemic Event Rates
> 2 to 3 months (n=55, 42)
|
1.21 events / subject-month
|
0.97 events / subject-month
|
|
Hypoglycemic Event Rates
> 3 to 4 months (n=52, 41)
|
0.87 events / subject-month
|
0.67 events / subject-month
|
|
Hypoglycemic Event Rates
> 4 to 5 months (n=52, 40)
|
0.96 events / subject-month
|
1.01 events / subject-month
|
|
Hypoglycemic Event Rates
> 5 to 6 months (n=52, 38)
|
0.69 events / subject-month
|
1.13 events / subject-month
|
|
Hypoglycemic Event Rates
> 8 to 9 months (n=51, 36)
|
0.59 events / subject-month
|
0.78 events / subject-month
|
|
Hypoglycemic Event Rates
> 9 to 10 months (n=51, 36)
|
0.50 events / subject-month
|
0.52 events / subject-month
|
|
Hypoglycemic Event Rates
> 10 to 11 months (n=49, 34)
|
0.75 events / subject-month
|
0.51 events / subject-month
|
SECONDARY outcome
Timeframe: 0 to 1 month to > 11 monthsPopulation: FAS, HbA1c=all randomized subjects who received at least 1 dose of study treatment, had a baseline HbA1c measurement, and had at least 1 HbA1c post-baseline measurement. Number of subjects with evaluable data: n=Inhaled Insulin, Subcutaneous Insulin.
An event was severe if the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL or the blood glucose was not measured, but the clinical manifestations were reversed by oral carbohydrates, subcutaneous glucagon, or intravenous glucose. Crude event rate=total events/100 subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.
Outcome measures
| Measure |
Inhaled Insulin
n=57 Participants
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
n=43 Participants
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Severe Hypoglcyemic Event Rates
0 to 1 month (n=57, 43)
|
1.71 events / 100 subject-months
|
2.35 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 1 to 2 months (n=56, 42)
|
1.79 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 2 to 3 months (n=55, 42)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 3 to 4 months (n=52, 41)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 4 to 5 months (n=52, 40)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 5 to 6 months (n=52, 38)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 6 to 7 months (n=52, 37)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 7 to 8 months (n=51, 36)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 8 to 9 months (n=51, 36)
|
1.96 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 9 to 10 months (n=51, 36)
|
2.01 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 10 to 11 months (n=49, 34)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
> 11 months (n=47, 33)
|
0.00 events / 100 subject-months
|
0.00 events / 100 subject-months
|
|
Severe Hypoglcyemic Event Rates
Overall (n=57, 43)
|
0.64 events / 100 subject-months
|
0.22 events / 100 subject-months
|
Adverse Events
Inhaled Insulin
Subcutaneous Insulin
Serious adverse events
| Measure |
Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.7%
1/59
|
0.00%
0/46
|
|
Cardiac disorders
Angina unstable
|
1.7%
1/59
|
0.00%
0/46
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/59
|
4.3%
2/46
|
|
Cardiac disorders
Myocardial infarction
|
1.7%
1/59
|
6.5%
3/46
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/59
|
2.2%
1/46
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/59
|
2.2%
1/46
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/59
|
2.2%
1/46
|
|
Gastrointestinal disorders
Vomiting projectile
|
0.00%
0/59
|
2.2%
1/46
|
|
General disorders
Chest pain
|
1.7%
1/59
|
0.00%
0/46
|
|
General disorders
Hypothermia
|
0.00%
0/59
|
2.2%
1/46
|
|
General disorders
Ill-defined disorder
|
0.00%
0/59
|
2.2%
1/46
|
|
General disorders
Implant site erosion
|
1.7%
1/59
|
0.00%
0/46
|
|
Infections and infestations
Appendicitis
|
0.00%
0/59
|
2.2%
1/46
|
|
Infections and infestations
Cellulitis
|
1.7%
1/59
|
0.00%
0/46
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/59
|
2.2%
1/46
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/59
|
2.2%
1/46
|
|
Infections and infestations
Pneumonia
|
5.1%
3/59
|
0.00%
0/46
|
|
Infections and infestations
Postoperative wound infection
|
1.7%
1/59
|
0.00%
0/46
|
|
Injury, poisoning and procedural complications
Drug administration error
|
0.00%
0/59
|
2.2%
1/46
|
|
Injury, poisoning and procedural complications
Radius fracture
|
1.7%
1/59
|
0.00%
0/46
|
|
Injury, poisoning and procedural complications
Rib fracture
|
1.7%
1/59
|
0.00%
0/46
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
1.7%
1/59
|
0.00%
0/46
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/59
|
2.2%
1/46
|
|
Investigations
Troponin increased
|
0.00%
0/59
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Dehydration
|
1.7%
1/59
|
0.00%
0/46
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
1.7%
1/59
|
0.00%
0/46
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.7%
1/59
|
2.2%
1/46
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
1.7%
1/59
|
0.00%
0/46
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/59
|
2.2%
1/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic
|
1.7%
1/59
|
0.00%
0/46
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
1.7%
1/59
|
0.00%
0/46
|
|
Nervous system disorders
Depressed level of consciousness
|
1.7%
1/59
|
0.00%
0/46
|
|
Nervous system disorders
Neuropathy peripheral
|
1.7%
1/59
|
0.00%
0/46
|
|
Nervous system disorders
Syncope
|
0.00%
0/59
|
2.2%
1/46
|
|
Renal and urinary disorders
Azotaemia
|
0.00%
0/59
|
2.2%
1/46
|
|
Renal and urinary disorders
Bladder neck obstruction
|
0.00%
0/59
|
2.2%
1/46
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
3.4%
2/59
|
0.00%
0/46
|
|
Vascular disorders
Arteriosclerosis
|
1.7%
1/59
|
0.00%
0/46
|
|
Vascular disorders
Hypertension
|
0.00%
0/59
|
2.2%
1/46
|
|
Vascular disorders
Hypotension
|
1.7%
1/59
|
0.00%
0/46
|
Other adverse events
| Measure |
Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
Subcutaneous Insulin
Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.8%
4/59
|
2.2%
1/46
|
|
Cardiac disorders
Coronary artery disease
|
3.4%
2/59
|
6.5%
3/46
|
|
Cardiac disorders
Myocardial infarction
|
1.7%
1/59
|
6.5%
3/46
|
|
Eye disorders
Vision blurred
|
3.4%
2/59
|
8.7%
4/46
|
|
Gastrointestinal disorders
Constipation
|
5.1%
3/59
|
0.00%
0/46
|
|
Gastrointestinal disorders
Diarrhoea
|
6.8%
4/59
|
6.5%
3/46
|
|
Gastrointestinal disorders
Nausea
|
6.8%
4/59
|
8.7%
4/46
|
|
Gastrointestinal disorders
Toothache
|
5.1%
3/59
|
2.2%
1/46
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
3/59
|
6.5%
3/46
|
|
General disorders
Asthenia
|
15.3%
9/59
|
10.9%
5/46
|
|
General disorders
Chest pain
|
6.8%
4/59
|
2.2%
1/46
|
|
General disorders
Fatigue
|
10.2%
6/59
|
6.5%
3/46
|
|
General disorders
Oedema peripheral
|
8.5%
5/59
|
13.0%
6/46
|
|
Immune system disorders
Seasonal allergy
|
5.1%
3/59
|
0.00%
0/46
|
|
Infections and infestations
Bronchitis
|
13.6%
8/59
|
4.3%
2/46
|
|
Infections and infestations
Gastroenteritis
|
5.1%
3/59
|
0.00%
0/46
|
|
Infections and infestations
Gastroenteritis viral
|
3.4%
2/59
|
6.5%
3/46
|
|
Infections and infestations
Influenza
|
6.8%
4/59
|
4.3%
2/46
|
|
Infections and infestations
Nasopharyngitis
|
16.9%
10/59
|
13.0%
6/46
|
|
Infections and infestations
Otitis media
|
5.1%
3/59
|
2.2%
1/46
|
|
Infections and infestations
Pneumonia
|
6.8%
4/59
|
4.3%
2/46
|
|
Infections and infestations
Sinusitis
|
5.1%
3/59
|
4.3%
2/46
|
|
Infections and infestations
Upper respiratory tract infection
|
20.3%
12/59
|
13.0%
6/46
|
|
Infections and infestations
Urinary tract infection
|
6.8%
4/59
|
2.2%
1/46
|
|
Injury, poisoning and procedural complications
Contusion
|
5.1%
3/59
|
4.3%
2/46
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
67.8%
40/59
|
65.2%
30/46
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.9%
7/59
|
4.3%
2/46
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.5%
5/59
|
10.9%
5/46
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.4%
2/59
|
10.9%
5/46
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/59
|
6.5%
3/46
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.1%
3/59
|
6.5%
3/46
|
|
Nervous system disorders
Dizziness
|
13.6%
8/59
|
15.2%
7/46
|
|
Nervous system disorders
Headache
|
16.9%
10/59
|
6.5%
3/46
|
|
Nervous system disorders
Neuropathy peripheral
|
6.8%
4/59
|
6.5%
3/46
|
|
Nervous system disorders
Tremor
|
6.8%
4/59
|
10.9%
5/46
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
6.8%
4/59
|
8.7%
4/46
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.5%
5/59
|
4.3%
2/46
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.2%
6/59
|
4.3%
2/46
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.1%
3/59
|
0.00%
0/46
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
5.1%
3/59
|
2.2%
1/46
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
11.9%
7/59
|
19.6%
9/46
|
|
Vascular disorders
Hypertension
|
10.2%
6/59
|
6.5%
3/46
|
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 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER