Chronic Obstructive Pulmonary Disease, Diabetes Mellitus
Conditions
Brief summary
A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics with Chronic Obstructive Pulmonary Disease.
Detailed description
Pfizer announced in October 2007 that it would stop marketing Exubera. At that time recruitment for study A2171030 was placed on hold. Nektar, the company from which Pfizer licensed Exubera, announced on April 9, 2008 that it had stopped its search for a new marketing partner. Accordingly, there will be no commercial availability of Exubera. As a result, study A2171030 was terminated on June 17, 2008. Neither safety nor efficacy reasons were the cause of the study termination.
Interventions
Subcutaneous short-acting insulin with dose adjusted according to premeal blood glucose plus oral antidiabetic agent(s) and/or either once or twice daily doses of either Ultralente or neutral protamine hagedorn (NPH) insulin, or a single bedtime dose of insulin glargine.
DRUGInhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose plus oral antidiabetic agent(s) and/or either once or twice daily doses of either Ultralente or NPH insulin, or a single bedtime dose of insulin glargine.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 77 Years
Healthy volunteers
No
Inclusion criteria
* Diabetes Mellitus (Type 1 or Type 2) currently controlled with injected insulin * Prior smokers with a fixed airflow obstruction at screening (FEV1/FVC \< 70%) and FEV1 \< 80% predicted and/or a history of chronic productive cough.
Exclusion criteria
* Poorly controlled, unstable or steroid-dependent COPD, insulin pump therapy, active smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52 | 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). |
| Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Other PFTs (Besides FEV1 and DLco) | Duration of the study | Other 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. |
| Bronchodilator Responsiveness as Determined by the Change in FEV1 | Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52 | 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. |
| Insulin Dose Responsiveness for FEV1 | Baseline, Week 9, Week 51 | 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). |
| Insulin Dose Responsiveness for DLco | Baseline, Week 9, Week 51 | 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). |
| Methacholine PC20 | Duration of the study | Methacholine 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. |
| Mean Weekly Number of Puffs of Short-Acting Bronchodilator Used | Duration of the study | All 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. |
| Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | 0 to 1 week to > 9 months | 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. |
| Incidence of Severe COPD Exacerbations | 0 to 1 week to > 9 months | 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. |
| Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) Questionnaires | Duration of the study | The 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. |
| Full Pulmonary Function Tests (PFTs) (Spirometry, Pre-Ipratropium and Pre-Insulin PFTs) | Duration of the study | Full 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. |
| Change From Baseline in Fasting Plasma Glucose | Baseline, Weeks 6, 12, 26, 39, 52 | Change from baseline: mean of (value of observed fasting plasma glucose in milligrams/deciliters (mg/dL) at treatment duration minus baseline value). |
| Change From Baseline in Body Weight | Baseline, Weeks 1, 2, 3, 4, 6, 9, 11, 12, 18, 26, 39, 50, 51, 52 | Change from baseline: mean of (value of observed body weight in kilograms (kg) at treatment duration minus baseline value). |
| Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52 | Intermediate-/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. |
| Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52 | 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. |
| Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52 | Intermediate/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Dose was adjusted for body weight (units divided by kg). |
| Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52 | 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). |
| Lipids | Duration of the study | Lipids collected: Total cholesterol, high-density lipoprotein, low-density lipoptrotein, and triglycerides. Lipids data were collected, but not analyzed. |
| Hypoglycemic Event Rates | 0 to1 month to > 11 months | 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. |
| Severe Hypoglcyemic Event Rates | 0 to 1 month to > 11 months | 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. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline, Weeks 6, 12, 26, 39, and 52 | Change from baseline: mean of (value of observed HbA1c at treatment duration minus baseline value). |
| Full PFTs (DLco, Pre-Ipratropium and Pre- Insulin PFTs) | Duration of the study | Full 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. |
Countries
Brazil, Canada, Costa Rica, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Insulin Inhaled insulin with dose adjusted according to premeal blood glucose plus basal insulin. | 59 |
| Subcutaneous Insulin Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin. | 46 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Subcutaneous Insulin | Inhaled Insulin | Total |
|---|---|---|---|
| Age, Customized 36 to 45 years | 3 participants | 1 participants | 4 participants |
| Age, Customized 46 to 55 years | 4 participants | 10 participants | 14 participants |
| Age, Customized 56 to 65 years | 23 participants | 20 participants | 43 participants |
| Age, Customized 66 to 75 years | 15 participants | 27 participants | 42 participants |
| Age, Customized > 75 years | 1 participants | 1 participants | 2 participants |
| Primary Diagnosis (Diabetes Type I or II) Type I | 6 participants | 7 participants | 13 participants |
| Primary Diagnosis (Diabetes Type I or II) Type II | 40 participants | 52 participants | 92 participants |
| Sex: Female, Male Female | 9 Participants | 17 Participants | 26 Participants |
| Sex: Female, Male Male | 37 Participants | 42 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 59 / — | 38 / — |
| serious Total, serious adverse events | 17 / — | 14 / — |
Outcome results
Primary
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)
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).
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled 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 |
| Inhaled Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 1 (n=51, 40) | -0.263 mL/min/mmHg | Standard Deviation 1.61 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 39 (n=47, 33) | -0.891 mL/min/mmHg | Standard Deviation 2.137 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 52 (n=45, 29) | -0.882 mL/min/mmHg | Standard Deviation 1.72 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 1 (n=51, 40) | -0.319 mL/min/mmHg | Standard Deviation 0.984 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 2 (n=51, 40) | -0.031 mL/min/mmHg | Standard Deviation 1.106 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 3 (n=47, 40) | 0.169 mL/min/mmHg | Standard Deviation 1.303 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 4 (n=50, 39) | -0.482 mL/min/mmHg | Standard Deviation 1.321 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 6 (n=52, 38) | -0.576 mL/min/mmHg | Standard Deviation 1.226 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 18 (n=51, 36) | -0.286 mL/min/mmHg | Standard Deviation 1.796 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 26 (n=52, 38) | -0.947 mL/min/mmHg | Standard Deviation 1.643 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco) | Week 12 (n=47, 40) | -0.534 mL/min/mmHg | Standard Deviation 1.506 |
Primary
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
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).
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 12 (n=48, 41) | -0.056 L | Standard Deviation 0.18 |
| Inhaled 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 |
| Inhaled Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 4 (n=50, 38) | -0.050 L | Standard Deviation 0.14 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 52 (n=45, 30) | -0.128 L | Standard Deviation 0.184 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 1 (n=52, 39) | -0.018 L | Standard Deviation 0.125 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 2 (n=51, 40) | -0.042 L | Standard Deviation 0.12 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 3 (n=47, 40) | -0.048 L | Standard Deviation 0.145 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 4 (n=50, 38) | -0.039 L | Standard Deviation 0.151 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 6 (n=53, 38) | -0.070 L | Standard Deviation 0.165 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 12 (n=48, 41) | -0.007 L | Standard Deviation 0.187 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 18 (n=52, 37) | -0.071 L | Standard Deviation 0.195 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 26 (n=52, 38) | -0.096 L | Standard Deviation 0.189 |
| Subcutaneous Insulin | Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Week 39, (n=47, 34) | -0.092 L | Standard Deviation 0.232 |
Secondary
Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) Questionnaires
The 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.
Time frame: Duration of the study
Secondary
Bronchodilator Responsiveness as Determined by the Change in FEV1
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.
Time frame: Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 18 (n=52, 37) | 6.700 percent change | Standard Deviation 6.02 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 4 (n=50, 38) | 5.177 percent change | Standard Deviation 7.211 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 26 (n=52, 38) | 5.585 percent change | Standard Deviation 5.592 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 1 (n=52, 39) | 4.890 percent change | Standard Deviation 5.727 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 2 (n=51, 40) | 6.132 percent change | Standard Deviation 6.2 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 3 (n=47, 40) | 6.346 percent change | Standard Deviation 7.469 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 6 (n=53, 38) | 5.988 percent change | Standard Deviation 6.034 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 12 (n=48, 41) | 6.473 percent change | Standard Deviation 8.994 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 39 (n=47, 34) | 6.634 percent change | Standard Deviation 5.829 |
| Inhaled Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 52 (n=45, 30) | 6.030 percent change | Standard Deviation 4.7 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 26 (n=52, 38) | 5.856 percent change | Standard Deviation 8.562 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 3 (n=47, 40) | 5.820 percent change | Standard Deviation 8.347 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 52 (n=45, 30) | 5.445 percent change | Standard Deviation 8.39 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 4 (n=50, 38) | 6.382 percent change | Standard Deviation 9.685 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 18 (n=52, 37) | 5.152 percent change | Standard Deviation 8.155 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 6 (n=53, 38) | 7.736 percent change | Standard Deviation 10.139 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 39 (n=47, 34) | 6.098 percent change | Standard Deviation 9.311 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 1 (n=52, 39) | 5.693 percent change | Standard Deviation 7.249 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 12 (n=48, 41) | 5.542 percent change | Standard Deviation 6.791 |
| Subcutaneous Insulin | Bronchodilator Responsiveness as Determined by the Change in FEV1 | Week 2 (n=51, 40) | 5.245 percent change | Standard Deviation 6.254 |
Secondary
Change From Baseline in Body Weight
Change from baseline: mean of (value of observed body weight in kilograms (kg) at treatment duration minus baseline value).
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 9, 11, 12, 18, 26, 39, 50, 51, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Body Weight | Week 12 (n=49, 41) | 0.42 kg | Standard Deviation 3.29 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 4 (n=53, 41) | 0.19 kg | Standard Deviation 1.98 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 18 (n=52, 37) | 0.40 kg | Standard Deviation 3.66 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 6 (n=54, 39) | 0.42 kg | Standard Deviation 2.26 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 26 (n=52, 38) | 0.85 kg | Standard Deviation 3.95 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 1 (n=52, 40) | 0.25 kg | Standard Deviation 1.62 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 39 (n=47, 34) | 0.61 kg | Standard Deviation 4.37 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 9 (n=47, 34) | 0.31 kg | Standard Deviation 2.93 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 50 (n=8, 6) | 1.75 kg | Standard Deviation 4.9 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 51 (n=23, 17) | 1.21 kg | Standard Deviation 4.82 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 3 (n=49, 41) | 0.19 kg | Standard Deviation 2.03 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 52 (n=43, 27) | 0.97 kg | Standard Deviation 5.65 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 11 (n=8, 8) | 0.03 kg | Standard Deviation 2.25 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 52 LOCF (n=59, 43) | 0.99 kg | Standard Deviation 4.2 |
| Inhaled Insulin | Change From Baseline in Body Weight | Week 2 (n=51, 40) | 0.26 kg | Standard Deviation 1.77 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 52 LOCF (n=59, 43) | 2.40 kg | Standard Deviation 4.79 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 4 (n=53, 41) | 0.24 kg | Standard Deviation 2.13 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 1 (n=52, 40) | 0.02 kg | Standard Deviation 0.98 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 2 (n=51, 40) | 0.15 kg | Standard Deviation 1.73 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 3 (n=49, 41) | 0.13 kg | Standard Deviation 1.9 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 6 (n=54, 39) | 0.26 kg | Standard Deviation 1.94 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 9 (n=47, 34) | 0.25 kg | Standard Deviation 2.31 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 11 (n=8, 8) | -0.14 kg | Standard Deviation 2.97 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 12 (n=49, 41) | 0.34 kg | Standard Deviation 3.69 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 18 (n=52, 37) | 0.90 kg | Standard Deviation 4.01 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 26 (n=52, 38) | 1.99 kg | Standard Deviation 4.03 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 39 (n=47, 34) | 2.43 kg | Standard Deviation 5.21 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 51 (n=23, 17) | 2.67 kg | Standard Deviation 3.28 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 52 (n=43, 27) | 3.32 kg | Standard Deviation 4.68 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Week 50 (n=8, 6) | 6.33 kg | Standard Deviation 9.06 |
Comparison: Week 190% CI: [-0.317, 2.084]
Comparison: Week 290% CI: [-0.728, 1.668]
Comparison: Week 390% CI: [-0.815, 1.579]
Comparison: Week 490% CI: [-0.793, 1.602]
Comparison: Week 690% CI: [-0.642, 1.766]
Comparison: Week 990% CI: [-0.809, 1.641]
Comparison: Week 1190% CI: [-1.416, 1.454]
Comparison: Week 1290% CI: [-1.127, 1.308]
Comparison: Week 1890% CI: [-1.551, 0.934]
Comparison: Week 2690% CI: [-2.123, 0.384]
Comparison: Week 3990% CI: [-2.968, -0.36]
Comparison: Week 5090% CI: [-3.829, -0.403]
Comparison: Week 5190% CI: [-3.204, -0.397]
Comparison: Week 5290% CI: [-3.384, -0.668]
Comparison: Week 52 LOCF90% CI: [-3.003, 0.101]
Secondary
Change From Baseline in Fasting Plasma Glucose
Change from baseline: mean of (value of observed fasting plasma glucose in milligrams/deciliters (mg/dL) at treatment duration minus baseline value).
Time frame: Baseline, Weeks 6, 12, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=52, 39) | -24.67 mg/dL | Standard Deviation 69.69 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=48, 39) | -30.73 mg/dL | Standard Deviation 52.99 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 26 (n=47, 38) | -34.92 mg/dL | Standard Deviation 61.63 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 39 (n=47, 33) | -20.45 mg/dL | Standard Deviation 56.62 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 52 (n=45, 31) | -23.40 mg/dL | Standard Deviation 65.77 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 52 (LOCF) (n=57, 43) | -28.55 mg/dL | Standard Deviation 65.85 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 52 (n=45, 31) | 12.37 mg/dL | Standard Deviation 58.01 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=52, 39) | 2.89 mg/dL | Standard Deviation 41.17 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 39 (n=47, 33) | 10.43 mg/dL | Standard Deviation 98.53 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=48, 39) | -0.18 mg/dL | Standard Deviation 46.25 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 52 (LOCF) (n=57, 43) | 2.36 mg/dL | Standard Deviation 66.51 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 26 (n=47, 38) | 10.45 mg/dL | Standard Deviation 62.8 |
Comparison: Week 690% CI: [-23.47, 14.518]
Comparison: Week 1290% CI: [-30.04, 8.232]
Comparison: Week 2690% CI: [-42.51, -3.166]
Comparison: Week 3990% CI: [-28.52, 12.075]
Comparison: Week 5290% CI: [-29.27, 12.616]
Comparison: Week 52 LOCF90% CI: [-13.7, 16.514]
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Change from baseline: mean of (value of observed HbA1c at treatment duration minus baseline value).
Time frame: Baseline, Weeks 6, 12, 26, 39, and 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 6 (n=56, 40) | -0.40 percent | Standard Deviation 0.81 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 12 (n=50, 41) | -0.53 percent | Standard Deviation 0.98 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 26 (n=52, 38) | -0.39 percent | Standard Deviation 0.96 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 39 (n=48, 35) | -0.34 percent | Standard Deviation 1.11 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 52 (n=46, 32) | -0.30 percent | Standard Deviation 1.1 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 52 LOCF (n=57, 43) | -0.28 percent | Standard Deviation 1.03 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 52 (n=46, 32) | -0.23 percent | Standard Deviation 0.84 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 6 (n=56, 40) | -0.48 percent | Standard Deviation 0.6 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 39 (n=48, 35) | -0.20 percent | Standard Deviation 1.01 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 12 (n=50, 41) | -0.42 percent | Standard Deviation 0.65 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 52 LOCF (n=57, 43) | -0.26 percent | Standard Deviation 0.79 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 26 (n=52, 38) | -0.32 percent | Standard Deviation 0.79 |
Comparison: Week 690% CI: [-0.17, 0.36]
Comparison: Week 1290% CI: [-0.27, 0.26]
Comparison: Week 2690% CI: [-0.29, 0.26]
Comparison: Week 3990% CI: [-0.36, 0.2]
Comparison: Week 5290% CI: [-0.23, 0.35]
Comparison: Week 52 LOCF90% CI: [-0.29, 0.31]
Secondary
Full PFTs (DLco, Pre-Ipratropium and Pre- Insulin PFTs)
Full 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.
Time frame: Duration of the study
Secondary
Full Pulmonary Function Tests (PFTs) (Spirometry, Pre-Ipratropium and Pre-Insulin PFTs)
Full 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.
Time frame: Duration of the study
Secondary
Hypoglycemic Event Rates
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.
Time frame: 0 to1 month to > 11 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Hypoglycemic Event Rates | > 2 to 3 months (n=55, 42) | 1.21 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 7 to 8 months (n=51, 36) | 0.67 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 4 to 5 months (n=52, 40) | 0.96 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 8 to 9 months (n=51, 36) | 0.59 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 1 to 2 months (n=56, 42) | 1.25 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 9 to 10 months (n=51, 36) | 0.50 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 5 to 6 months (n=52, 38) | 0.69 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 10 to 11 months (n=49, 34) | 0.75 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 3 to 4 months (n=52, 41) | 0.87 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 11 months (n=47, 33) | 0.62 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | > 6 to 7 months (n=52, 37) | 0.62 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | Overall (n=57, 43) | 0.89 events / subject-month |
| Inhaled Insulin | Hypoglycemic Event Rates | 0 to 1 month (n=57, 43) | 1.76 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Overall (n=57, 43) | 0.84 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | 0 to 1 month (n=57, 43) | 1.36 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 1 to 2 months (n=56, 42) | 0.98 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 2 to 3 months (n=55, 42) | 0.97 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 3 to 4 months (n=52, 41) | 0.67 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 4 to 5 months (n=52, 40) | 1.01 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 5 to 6 months (n=52, 38) | 1.13 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 6 to 7 months (n=52, 37) | 0.92 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 7 to 8 months (n=51, 36) | 0.75 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 8 to 9 months (n=51, 36) | 0.78 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 9 to 10 months (n=51, 36) | 0.52 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 10 to 11 months (n=49, 34) | 0.51 events / subject-month |
| Subcutaneous Insulin | Hypoglycemic Event Rates | > 11 months (n=47, 33) | 0.26 events / subject-month |
Secondary
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
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.
Time frame: 0 to 1 week to > 9 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | 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) |
| Inhaled Insulin | 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) |
| Inhaled 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) |
| Inhaled Insulin | 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) |
| Inhaled Insulin | 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) |
| Inhaled Insulin | 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) |
| Inhaled Insulin | 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) |
| Inhaled Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 9 months (n=50, 35) | 0.01 events/subject-month (crude event rate) |
| Inhaled Insulin | 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) |
| Inhaled Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | Overall (n=59, 43) | 0.02 events/subject-month (crude event rate) |
| Inhaled Insulin | 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) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | Overall (n=59, 43) | 0.02 events/subject-month (crude event rate) |
| Subcutaneous Insulin | 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) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 1 to 2 weeks (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous 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) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 3 to 4 weeks (n=59, 42) | 0.10 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 4 to 6 weeks (n=57, 42) | 0.05 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 6 to 9 weeks (n=56, 42) | 0.03 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 9 to 12 weeks (n=55, 41) | 0.07 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 3 to 6 months (n=52, 41) | 0.01 events/subject-month (crude event rate) |
| Subcutaneous Insulin | 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) |
| Subcutaneous Insulin | Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | > 9 months (n=50, 35) | 0.02 events/subject-month (crude event rate) |
Secondary
Incidence of Severe COPD Exacerbations
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.
Time frame: 0 to 1 week to > 9 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 2 to 3 weeks (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 6 to 9 weeks (n=56, 42) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 1 to 2 weeks (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 9 to 12 weeks (n=55, 41) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 3 to 4 weeks (n=59, 42) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 3 to 6 months (n=52, 41) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | 0 to 1 week (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 9 months (n=50, 35) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 4 to 6 weeks (n=57, 42) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | Overall (n= 59, 43) | 0.00 events/subject-month (crude event rate) |
| Inhaled Insulin | Incidence of Severe COPD Exacerbations | > 6 to 9 months (n=52, 37) | 0.01 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | Overall (n= 59, 43) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 6 to 9 months (n=52, 37) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | 0 to 1 week (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 1 to 2 weeks (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 2 to 3 weeks (n=59, 43) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 3 to 4 weeks (n=59, 42) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 4 to 6 weeks (n=57, 42) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 6 to 9 weeks (n=56, 42) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 9 to 12 weeks (n=55, 41) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 3 to 6 months (n=52, 41) | 0.00 events/subject-month (crude event rate) |
| Subcutaneous Insulin | Incidence of Severe COPD Exacerbations | > 9 months (n=50, 35) | 0.00 events/subject-month (crude event rate) |
Secondary
Insulin Dose Responsiveness for DLco
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).
Time frame: Baseline, Week 9, Week 51
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Insulin Dose Responsiveness for DLco | Week 9, 10 minutes (n=41, 30) | -0.182 mL/min/mmHg | Standard Deviation 1.015 |
| Inhaled Insulin | Insulin Dose Responsiveness for DLco | Week 51, 60 minutes (n=44, 31) | -0.395 mL/min/mmHg | Standard Deviation 0.885 |
| Inhaled Insulin | Insulin Dose Responsiveness for DLco | Week 9, 60 minutes (n=42, 29) | 0.013 mL/min/mmHg | Standard Deviation 2.288 |
| Inhaled Insulin | Insulin Dose Responsiveness for DLco | Baseline, 60 minutes (n=49, 39) | -0.597 mL/min/mmHg | Standard Deviation 1.102 |
| Inhaled Insulin | Insulin Dose Responsiveness for DLco | Week 51, 10 minutes (n=44, 31) | -0.465 mL/min/mmHg | Standard Deviation 0.781 |
| Inhaled Insulin | Insulin Dose Responsiveness for DLco | Baseline, 10 minutes (n=48, 39) | -0.461 mL/min/mmHg | Standard Deviation 1.157 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for DLco | Week 51, 60 minutes (n=44, 31) | -0.163 mL/min/mmHg | Standard Deviation 1.211 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for DLco | Baseline, 10 minutes (n=48, 39) | -0.195 mL/min/mmHg | Standard Deviation 0.707 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for DLco | Baseline, 60 minutes (n=49, 39) | -0.160 mL/min/mmHg | Standard Deviation 1.217 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for DLco | Week 9, 10 minutes (n=41, 30) | -0.238 mL/min/mmHg | Standard Deviation 1.505 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for DLco | Week 9, 60 minutes (n=42, 29) | -0.373 mL/min/mmHg | Standard Deviation 1.574 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for DLco | Week 51, 10 minutes (n=44, 31) | 0.054 mL/min/mmHg | Standard Deviation 1.204 |
Secondary
Insulin Dose Responsiveness for FEV1
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).
Time frame: Baseline, Week 9, Week 51
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Insulin Dose Responsiveness for FEV1 | Baseline, 60 minutes (n=50, 39) | -0.004 L | Standard Deviation 0.096 |
| Inhaled Insulin | Insulin Dose Responsiveness for FEV1 | Baseline, 10 minutes (n=50, 39) | 0.009 L | Standard Deviation 0.076 |
| Inhaled Insulin | Insulin Dose Responsiveness for FEV1 | Week 9, 10 minutes (n=42, 31) | -0.004 L | Standard Deviation 0.11 |
| Inhaled Insulin | Insulin Dose Responsiveness for FEV1 | Week 9, 60 minutes (n=42, 30) | 0.011 L | Standard Deviation 0.109 |
| Inhaled Insulin | Insulin Dose Responsiveness for FEV1 | Week 51, 10 minutes (n=46, 31) | -0.021 L | Standard Deviation 0.121 |
| Inhaled Insulin | Insulin Dose Responsiveness for FEV1 | Week 51, 60 minutes (n=45, 31) | 0.005 L | Standard Deviation 0.115 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for FEV1 | Week 51, 10 minutes (n=46, 31) | -0.002 L | Standard Deviation 0.084 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for FEV1 | Baseline, 60 minutes (n=50, 39) | 0.020 L | Standard Deviation 0.127 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for FEV1 | Week 9, 10 minutes (n=42, 31) | 0.016 L | Standard Deviation 0.096 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for FEV1 | Week 9, 60 minutes (n=42, 30) | 0.030 L | Standard Deviation 0.116 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for FEV1 | Baseline, 10 minutes (n=50, 39) | 0.022 L | Standard Deviation 0.106 |
| Subcutaneous Insulin | Insulin Dose Responsiveness for FEV1 | Week 51, 60 minutes (n=45, 31) | -0.020 L | Standard Deviation 0.141 |
Secondary
Lipids
Lipids collected: Total cholesterol, high-density lipoprotein, low-density lipoptrotein, and triglycerides. Lipids data were collected, but not analyzed.
Time frame: Duration of the study
Secondary
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)
Intermediate/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Dose was adjusted for body weight (units divided by kg).
Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 52, (n=43, 27) | 0.56 Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 2 (n=50, 40) | 0.48 Units/kg | Standard Deviation 0.2 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 3 (n=49, 39) | 0.50 Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 4 (n=50, 41) | 0.50 Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 6 (n=53, 39) | 0.51 Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 9 (n=46, 34) | 0.57 Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 12 (n=49, 41) | 0.52 Units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 18 (n=51, 37) | 0.55 Units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 26 (n=51, 38) | 0.55 Units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 39 (n=47, 34) | 0.54 Units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight) | Week 1 (n=51, 40) | 0.48 Units/kg | Standard Deviation 0.19 |
Secondary
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)
Intermediate-/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups.
Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 39 (n=49, 35) | 49.99 Units | Standard Deviation 29 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 6 (n=54, 40) | 49.56 Units | Standard Deviation 26.61 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 2 (n=50, 41) | 44.96 Units | Standard Deviation 22.5 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 12 (n=51, 41) | 49.23 Units | Standard Deviation 28.46 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 9 (n=47, 35) | 48.68 Units | Standard Deviation 28.61 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 18 (n=51, 40) | 50.87 Units | Standard Deviation 29.32 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 3 (n=51, 39) | 47.04 Units | Standard Deviation 24.36 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 26 (n=51, 38) | 50.47 Units | Standard Deviation 28.83 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 1 (n=53, 40) | 43.78 Units | Standard Deviation 22.2 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 52 (n=48, 34) | 50.66 Units | Standard Deviation 30.63 |
| Inhaled Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 4 (n=52, 41) | 47.50 Units | Standard Deviation 25.94 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 52 (n=48, 34) | 53.39 Units | Standard Deviation 26.32 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 39 (n=49, 35) | 53.10 Units | Standard Deviation 26.11 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 1 (n=53, 40) | 48.18 Units | Standard Deviation 23.44 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 2 (n=50, 41) | 48.04 Units | Standard Deviation 24.33 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 3 (n=51, 39) | 50.53 Units | Standard Deviation 24.44 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 4 (n=52, 41) | 50.30 Units | Standard Deviation 25.61 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 9 (n=47, 35) | 56.72 Units | Standard Deviation 25.89 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 12 (n=51, 41) | 52.32 Units | Standard Deviation 29.49 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 18 (n=51, 40) | 53.83 Units | Standard Deviation 29.34 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 26 (n=51, 38) | 55.78 Units | Standard Deviation 28.11 |
| Subcutaneous Insulin | Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight) | Week 6 (n=54, 40) | 51.34 Units | Standard Deviation 25.91 |
Secondary
Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight)
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).
Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled Insulin | 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 |
| Inhaled 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 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 52 (n=43, 27) | 0.40 mg/kg, Units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 1 (n=52, 40) | 0.33 mg/kg, Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 6 (n=54, 39) | 0.34 mg/kg, Units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 2 (n=51, 40) | 0.33 mg/kg, Units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 3 (n=49, 39) | 0.33 mg/kg, Units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 4 (n=51, 41) | 0.32 mg/kg, Units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 9 (n=47, 34) | 0.36 mg/kg, Units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 12 (n=49, 41) | 0.34 mg/kg, Units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 18 (n=52, 37) | 0.37 mg/kg, Units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 26 (n=52, 38) | 0.38 mg/kg, Units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Adjusted for Body Weight) | Week 39 (n=47, 34) | 0.38 mg/kg, Units/kg | Standard Deviation 0.25 |
Secondary
Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
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.
Time frame: Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 3 (n=52, 39) | 14.10 mg, Units | Standard Deviation 6.89 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 9 (n=48, 35) | 15.82 mg, Units | Standard Deviation 7.41 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 2 (n=51, 41) | 13.03 mg, Units | Standard Deviation 6.63 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 12 (n=52, 41) | 15.64 mg, Units | Standard Deviation 7.8 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 4 (n=53, 41) | 14.17 mg, Units | Standard Deviation 7.28 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 18 (n=52, 40) | 16.47 mg, Units | Standard Deviation 7.48 |
| Inhaled 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 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 39 (n=49, 35) | 17.22 mg, Units | Standard Deviation 8.6 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 6 (n=55, 40) | 15.17 mg, Units | Standard Deviation 7.2 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 52 (n=48, 34) | 16.85 mg, Units | Standard Deviation 9.52 |
| Inhaled Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 26 (n=52, 38) | 16.71 mg, Units | Standard Deviation 8.05 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 52 (n=48, 34) | 39.28 mg, Units | Standard Deviation 25.13 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 26 (n=52, 38) | 37.73 mg, Units | Standard Deviation 26.14 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 1 (n=54, 40) | 32.74 mg, Units | Standard Deviation 21.59 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 2 (n=51, 41) | 32.08 mg, Units | Standard Deviation 22.25 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 3 (n=52, 39) | 32.88 mg, Units | Standard Deviation 21.6 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 4 (n=53, 41) | 31.85 mg, Units | Standard Deviation 22.29 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 6 (n=55, 40) | 33.42 mg, Units | Standard Deviation 22.72 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 9 (n=48, 35) | 36.65 mg, Units | Standard Deviation 22.94 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 12 (n=52, 41) | 33.58 mg, Units | Standard Deviation 23.94 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 18 (n=52, 40) | 35.36 mg, Units | Standard Deviation 26.06 |
| Subcutaneous Insulin | Mean Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Week 39 (n=49, 35) | 37.47 mg, Units | Standard Deviation 26.2 |
Secondary
Mean Weekly Number of Puffs of Short-Acting Bronchodilator Used
All 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.
Time frame: Duration of the study
Secondary
Methacholine PC20
Methacholine 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.
Time frame: Duration of the study
Secondary
Other PFTs (Besides FEV1 and DLco)
Other 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.
Time frame: Duration of the study
Secondary
Severe Hypoglcyemic Event Rates
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.
Time frame: 0 to 1 month to > 11 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 3 to 4 months (n=52, 41) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 7 to 8 months (n=51, 36) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 1 to 2 months (n=56, 42) | 1.79 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 8 to 9 months (n=51, 36) | 1.96 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 4 to 5 months (n=52, 40) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 9 to 10 months (n=51, 36) | 2.01 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | 0 to 1 month (n=57, 43) | 1.71 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 10 to 11 months (n=49, 34) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 5 to 6 months (n=52, 38) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 11 months (n=47, 33) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 2 to 3 months (n=55, 42) | 0.00 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | Overall (n=57, 43) | 0.64 events / 100 subject-months |
| Inhaled Insulin | Severe Hypoglcyemic Event Rates | > 6 to 7 months (n=52, 37) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | Overall (n=57, 43) | 0.22 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | 0 to 1 month (n=57, 43) | 2.35 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 1 to 2 months (n=56, 42) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 3 to 4 months (n=52, 41) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 4 to 5 months (n=52, 40) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 5 to 6 months (n=52, 38) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 6 to 7 months (n=52, 37) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 7 to 8 months (n=51, 36) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 8 to 9 months (n=51, 36) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 9 to 10 months (n=51, 36) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 10 to 11 months (n=49, 34) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 11 months (n=47, 33) | 0.00 events / 100 subject-months |
| Subcutaneous Insulin | Severe Hypoglcyemic Event Rates | > 2 to 3 months (n=55, 42) | 0.00 events / 100 subject-months |