Diabetes Mellitus, Type 1
Conditions
Brief summary
This study is being done to find out the good and bad effects of a drug that is not approved for sale and the effects if any on measures of pulmonary function in adult males and females with type 1 diabetes mellitus. The drug is called EXUBERA (inhaled insulin). This study included a 2-year comparative treatment period followed by a 6-month follow-up period during which inhaled insulin-treated subjects were switched back to subcutaneous short-acting insulin. After this follow-up period, all eligible subjects entered a comparative extension period that was to last for 5 years. When the comparative portion of the study was terminated, all subjects were requested to return for a final extension follow-up month 3 visit.
Detailed description
Pfizer announced in October 2007 that it would stop marketing Exubera. 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 A2171022 was terminated on June 9, 2008. Neither safety nor efficacy reasons were the cause of the study termination.
Interventions
Subcutaneous insulin with dose adjusted according to premeal blood glucose
DRUGInhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes mellitus
Exclusion criteria
* severe asthma or COPD * smoking * brittle diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline through Extension Follow-up Month 3 | Change from Baseline: mean of (value of observed forced expiratory volume in the first second of forced exhalation \[FEV1\] in liters \[L\] at observation minus Baseline value). |
| Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 3 through Extension Follow-up 3 | Number of subjects with a post-baseline Forced Expiratory Volume in One Second (FEV1) decrease of ≥ 15 % \[(baseline observed value minus visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrent illness, a repeat FEV1 was performed. |
| Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Baseline through Extension Follow-up Month 3 | Change from Baseline: mean of (value of Carbon Monoxide Diffusing Capacity \[DLco\] measured in milliters/minutes/millimeters of mercury \[mL/min/mmHg\] at observation minus Baseline value). |
| Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 3 through Extension Follow-up Month 3 | Number of subjects with a post-baseline Carbon Monoxide Diffusing Capacity (DLco) decrease of ≥ 20% \[(baseline observed value minus visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrent illness, a repeat DLco was performed. |
| Annual Rate of Change in Forced Expiratory Volume in 1 Second (FEV1) | Week -2 through Extension Follow-up Month 6 or end of study | Annual rate of change in FEV1 calculated as slope over time \[visit\] for forced expiratory volume in 1 second measured as liters per year (L/yr). |
| Annual Rate of Change in Carbon Monoxide Diffusion Capacity (DLco) | Week -2 through Extension Follow-up Month 6 or end of study | Annual rate of change in DLco calculated as slope over time (visit) measured as milliliters per minute per millimeters of hemoglobin per year (ml/min/mmHg/yr). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 3 through Extension Month 39 | Total daily dose of long-acting insulin adjusted for body weight (units per kilogram \[kg\]). Long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups. |
| Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 3 through Extension Month 39 | Total daily dose of short-acting insulin 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. |
| Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 3 through Extension Month 39 | Total Daily Short-Acting Insulin Dose adjusted for body weight (milligrams \[mg\] or units divided by kilograms \[kg\]). 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. |
| Baseline Dyspnea Index (BDI) | Week - 1 | Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI score range 0 (very severe impairment) to 4 (no impairment) scaled to a BDI focal score (0-12). Lower score indicates greater impairment. |
| Transition Dyspnea Index (TDI) | Week 4 through ,Extension Follow-up Month 6 and every 6 months thereafter or end of study | Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI score range -3 (major deterioration) to +3 (major improvement); sum of all domains yields the TDI focal score (-9 to +9); lower score indicates greater deterioration. Compared to previous scoring to determine deterioration or improvement. |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline through Extension Follow-up Month 3 | Change from Baseline: mean of (value of Glycosylated Hemoglobin \[HbA1c\] at observation minus Baseline value). |
| Cough Questionnaire | Week 0 and if indicated through Extension Follow up Month 3 | Subject completed cough questionnaire with reference to the past 4 weeks. Six question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (subcutaneous \[SC\] or inhaled), and productivity of cough; range 0 (no symptoms) to 4 (severe symptoms). Questionnaire was administered at Week 0 and then at subsequent visits only if cough was identified as an adverse event not explained by a concomitant condition, such as an upper respiratory tract infection. |
| Forced Vital Capacity (FVC) | Week -3 through Extension Follow-up Month 6 or End of Study | Forced Vital Capacity (FVC) measured in liters (L). |
| Total Lung Capacity (TLC) | Week -3 through Extension Follow-up Month 6 or End of Study | Total Lung Capacity measured in liters (L). |
| Insulin Antibodies | Baseline through Extension Month 39 | Median insulin antibodies at each visit measured in micro units per milliliter (microU/mL). |
| Lipids | Week -4 through Month 24 | Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides measured as milligrams per deciliter (mg/dL). |
| Hypoglycemic Event Rates | Month 1 through Extension Month 39 | A Hypoglycemic event was identified by characteristic symptoms of hypoglycemia with no blood glucose check with prompt resolution with food intake, subcutaneous glucagon, or intravenouus glucose; characteristic symptoms with blood glucose of 59 milligrams per deciliter (mg/dL) (3.2 mmol/L) or less with blood glucose check; or any glucose measurement of 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Subject months = elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject month of treatment. |
| Severe Hypoglycemic Event Rates | Month 1 through Extension Month 39 | Severe hypoglycemic event = all 3 of the following criteria were met: subject unable to treat self, exhbited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness); and blood glucose measurement was ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, subcutaneous glucagon, or i.v. glucose. Subject months = elapsed number of months subject was in study in each time interval. Crude event rate = total events divided by subject months \* 100. |
| Change From Baseline in Fasting Plasma Glucose | Baseline through Extension Follow-up Month 3 | Change from Baseline: mean of (value of fasting plasma glucose \[milligrams per deciliter (mg/dL)\] at observation minus Baseline value). |
| Change From Baseline Body Weight | Baseline through Extension Follow-up Month 3 | Body weight: mean Baseline and change from Baseline in kilograms (kg). Change from baseline = mean body weight in kilograms (kg) at observation minus mean baseline body weight. |
| Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 3 through Extension Month 39 | Total Daily Long-Acting Insulin Dose Unadjusted for Body Weight; long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups. |
Countries
Argentina, Brazil, Canada, Mexico, United States
Participant flow
Recruitment details
A total of 64 centers took part in the study between 09 May 2002 and 08 December 2008.
Pre-assignment details
At the screening visit and during the 4-week run-in phase all subjects received a subcutaneous insulin regimen consisting of 2 to 3 doses per day of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 doses daily of intermediate-/long-acting insulin (NPH insulin or Ultralente), or insulin glargine once daily at bedtime.
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Insulin Inhaled insulin (Exubera®) with dose adjusted according to premeal blood glucose plus basal insulin. | 290 |
| Subcutaneous Insulin Subcutaneous insulin with dose adjusted according to premeal blood glucose plus basal insulin. | 290 |
| Total | 580 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 5 |
| Overall Study | Adverse Event 4 Days after Last Dose | 1 | 0 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Laboratory Abnormality | 2 | 0 |
| Overall Study | Lack of Efficacy | 13 | 1 |
| Overall Study | Lost to Follow-up | 8 | 24 |
| Overall Study | Other | 23 | 19 |
| Overall Study | Withdrawal by Subject | 33 | 42 |
| Overall Study | Withdrew prior to study treatment | 1 | 1 |
Baseline characteristics
| Characteristic | Inhaled Insulin | Subcutaneous Insulin | Total |
|---|---|---|---|
| Age, Customized 18 to 25 | 48 years | 53 years | 101 years |
| Age, Customized 26 to 35 | 81 years | 96 years | 177 years |
| Age, Customized 36 to 45 | 94 years | 71 years | 165 years |
| Age, Customized 46 to 55 | 52 years | 48 years | 100 years |
| Age, Customized 56 to 65 | 15 years | 22 years | 37 years |
| Sex: Female, Male Female | 121 Participants | 129 Participants | 250 Participants |
| Sex: Female, Male Male | 169 Participants | 161 Participants | 330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 290 / 290 | 289 / 290 |
| serious Total, serious adverse events | 50 / 290 | 65 / 290 |
Outcome results
Primary
Annual Rate of Change in Carbon Monoxide Diffusion Capacity (DLco)
Annual rate of change in DLco calculated as slope over time (visit) measured as milliliters per minute per millimeters of hemoglobin per year (ml/min/mmHg/yr).
Time frame: Week -2 through Extension Follow-up Month 6 or end of study
Population: FAS FEV1. Due to early termination of the study a limited set of analyses were undertaken and results of the annual rate of change in DLco were not summarized as planned.
Primary
Annual Rate of Change in Forced Expiratory Volume in 1 Second (FEV1)
Annual rate of change in FEV1 calculated as slope over time \[visit\] for forced expiratory volume in 1 second measured as liters per year (L/yr).
Time frame: Week -2 through Extension Follow-up Month 6 or end of study
Population: FAS FEV1. Due to early termination of the study a limited set of analyses were undertaken and results of the Annual Rate of Change in FEV1 were not summarized as planned.
Primary
Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco)
Change from Baseline: mean of (value of Carbon Monoxide Diffusing Capacity \[DLco\] measured in milliters/minutes/millimeters of mercury \[mL/min/mmHg\] at observation minus Baseline value).
Time frame: Baseline through Extension Follow-up Month 3
Population: FAS FEV1; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively. Due to study termination, originally planned inferential analysis change from Month 3 to extension Month 60 was not done.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Baseline (n=283, 281) | 28.09 mL/min/mmHg | Standard Deviation 6.2 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 6 (n=158,169) | -1.38 mL/min/mmHg | Standard Deviation 2.37 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 21 (n=218, 224) | -1.29 mL/min/mmHg | Standard Deviation 2.49 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 9 (n=151,163) | -1.17 mL/min/mmHg | Standard Deviation 2.52 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 6 (n=262, 273) | -1.17 mL/min/mmHg | Standard Deviation 2.16 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 12 (n=152,161) | -1.70 mL/min/mmHg | Standard Deviation 2.46 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 24 (n=208, 219) | -1.28 mL/min/mmHg | Standard Deviation 2.29 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 15 (n=143,160) | -1.70 mL/min/mmHg | Standard Deviation 2.27 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 15 (n=235, 249) | -1.16 mL/min/mmHg | Standard Deviation 2.17 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 18 (n=148,159) | -1.67 mL/min/mmHg | Standard Deviation 2.36 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Follow-up Month 1 (n=242,208) | -0.81 mL/min/mmHg | Standard Deviation 2.2 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 21 (n=144,156) | -1.51 mL/min/mmHg | Standard Deviation 2.59 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 24 (n=140,152) | -1.63 mL/min/mmHg | Standard Deviation 2.46 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 9 (n=250, 266) | -1.16 mL/min/mmHg | Standard Deviation 2.09 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 27 (n=136,144) | -1.25 mL/min/mmHg | Standard Deviation 2.65 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Follow-up Month 3 (n=247,225) | -0.77 mL/min/mmHg | Standard Deviation 2.46 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 30 (n=135,146) | -1.36 mL/min/mmHg | Standard Deviation 2.54 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 3 (n=277, 264) | -1.09 mL/min/mmHg | Standard Deviation 1.73 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 33 (n=127,139) | -1.31 mL/min/mmHg | Standard Deviation 2.54 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Follow-up Month 6 (n=240,218) | -0.77 mL/min/mmHg | Standard Deviation 2.36 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 36 (n=105,122) | -1.53 mL/min/mmHg | Standard Deviation 2.53 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 12 (n=241, 258) | -1.40 mL/min/mmHg | Standard Deviation 2.15 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 39 (n=52, 64) | -2.02 mL/min/mmHg | Standard Deviation 3.72 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 1 (n=166,175) | -1.15 mL/min/mmHg | Standard Deviation 2.54 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 39 (LOCF) (n=177, 187) | -1.66 mL/min/mmHg | Standard Deviation 2.9 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 18 (n=227, 232) | -1.21 mL/min/mmHg | Standard Deviation 2.28 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Follow Up Month 3 (n=115, 101) | -0.89 mL/min/mmHg | Standard Deviation 2.35 |
| Inhaled Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 3 (n=161,173) | -1.43 mL/min/mmHg | Standard Deviation 2.37 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Follow Up Month 3 (n=115, 101) | -1.11 mL/min/mmHg | Standard Deviation 2.59 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 15 (n=235, 249) | -0.42 mL/min/mmHg | Standard Deviation 2.17 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 21 (n=144,156) | -0.88 mL/min/mmHg | Standard Deviation 2.64 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Baseline (n=283, 281) | 27.18 mL/min/mmHg | Standard Deviation 6.4 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 3 (n=277, 264) | -0.29 mL/min/mmHg | Standard Deviation 1.71 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 6 (n=262, 273) | -0.26 mL/min/mmHg | Standard Deviation 1.85 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 9 (n=250, 266) | -0.41 mL/min/mmHg | Standard Deviation 1.91 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 18 (n=227, 232) | -0.45 mL/min/mmHg | Standard Deviation 2.22 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 21 (n=218, 224) | -0.56 mL/min/mmHg | Standard Deviation 2.07 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 24 (n=208, 219) | -0.71 mL/min/mmHg | Standard Deviation 2.4 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Follow-up Month 1 (n=242,208) | -0.81 mL/min/mmHg | Standard Deviation 2.42 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Follow-up Month 3 (n=247,225) | -0.80 mL/min/mmHg | Standard Deviation 2.1 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Follow-up Month 6 (n=240,218) | -0.67 mL/min/mmHg | Standard Deviation 2.28 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 1 (n=166,175) | -0.55 mL/min/mmHg | Standard Deviation 2.35 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 3 (n=161,173) | -0.73 mL/min/mmHg | Standard Deviation 2.45 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 6 (n=158,169) | -0.78 mL/min/mmHg | Standard Deviation 2.54 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 9 (n=151,163) | -0.74 mL/min/mmHg | Standard Deviation 2.57 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 12 (n=152,161) | -0.70 mL/min/mmHg | Standard Deviation 2.6 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 15 (n=143,160) | -0.72 mL/min/mmHg | Standard Deviation 2.94 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 18 (n=148,159) | -1.02 mL/min/mmHg | Standard Deviation 2.72 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 24 (n=140,152) | -0.70 mL/min/mmHg | Standard Deviation 2.72 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 27 (n=136,144) | -0.76 mL/min/mmHg | Standard Deviation 2.75 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 30 (n=135,146) | -0.75 mL/min/mmHg | Standard Deviation 2.59 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 33 (n=127,139) | -0.81 mL/min/mmHg | Standard Deviation 2.55 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 36 (n=105,122) | -0.96 mL/min/mmHg | Standard Deviation 2.82 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 39 (n=52, 64) | -0.93 mL/min/mmHg | Standard Deviation 2.59 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Extension Month 39 (LOCF) (n=177, 187) | -0.90 mL/min/mmHg | Standard Deviation 2.55 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Month 12 (n=241, 258) | -0.41 mL/min/mmHg | Standard Deviation 2.15 |
Comparison: Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.981, -0.506]ANCOVA
Comparison: Month 6; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.073, -0.522]ANCOVA
Comparison: Month 9; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.949, -0.384]ANCOVA
Comparison: Month 12; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.123, -0.528]ANCOVA
Comparison: Month 15; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.923, -0.296]ANCOVA
Comparison: Month 18; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.91, -0.245]ANCOVA
Comparison: Month 21; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.962, -0.263]ANCOVA
Comparison: Month 24; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.736, -0.034]ANCOVA
Comparison: Follow-up Month 1; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.197, 0.497]ANCOVA
Comparison: Follow-up Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.16, 0.492]ANCOVA
Comparison: Follow-up Month 6; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.274, 0.411]ANCOVA
Comparison: Extension Month 1; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.876, -0.043]ANCOVA
Comparison: Extension Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.986, -0.172]ANCOVA
Comparison: Extension Month 6; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.88, -0.04]ANCOVA
Comparison: Extension Month 9; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.822, 0.053]ANCOVA
Comparison: Extension Month 12; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.372, -0.487]ANCOVA
Comparison: Extension Month 15; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.296, -0.351]ANCOVA
Comparison: Extension Month 18; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.965, -0.084]ANCOVA
Comparison: Extension Month 21; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.104, -0.191]ANCOVA
Comparison: Extension Month 24; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.34, -0.367]ANCOVA
Comparison: Extension Month 27; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.89, 0.111]ANCOVA
Comparison: Extension Month 30; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.119, -0.153]ANCOVA
Comparison: Extension Month 33; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1, -0.043]ANCOVA
Comparison: Extension Month 36; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.315, -0.173]ANCOVA
Comparison: Extension Month 39; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-2.42, -0.335]ANCOVA
Comparison: Extension Month 39 (LOCF); Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-1.183, -0.258]ANCOVA
Comparison: Extension Follow Up Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.594, 0.472]ANCOVA
Primary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Change from Baseline: mean of (value of observed forced expiratory volume in the first second of forced exhalation \[FEV1\] in liters \[L\] at observation minus Baseline value).
Time frame: Baseline through Extension Follow-up Month 3
Population: Full Analysis Set (FAS) FEV1: received at least 1 dose of study drug, had a Baseline FEV1, and at least 1 post-baseline FEV1. Due to study termination, originally planned inferential analysis for change from Month 3 through extension Month 60 was not done. Cross reference outcome measure: change from baseline in FEV1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 6 (n=158, 170) | -0.15 liters | Standard Deviation 0.19 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 12 (n=242, 259) | -0.08 liters | Standard Deviation 0.14 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 9 (n=151, 164) | -0.16 liters | Standard Deviation 0.18 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 24 (n=211, 219) | -0.12 liters | Standard Deviation 0.17 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 12 (n=152,161) | -0.17 liters | Standard Deviation 0.19 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 3 (n=277, 263) | -0.04 liters | Standard Deviation 0.12 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 15 (n=153,162) | -0.16 liters | Standard Deviation 0.19 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 1 (n=242, 209) | -0.11 liters | Standard Deviation 0.17 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 18 (n=148,160) | -0.18 liters | Standard Deviation 0.2 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 15 (n=236, 250) | -0.09 liters | Standard Deviation 0.16 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 21 (n=144,158) | -0.17 liters | Standard Deviation 0.19 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 3 (n=249, 225) | -0.10 liters | Standard Deviation 0.16 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 24 (n=141,153) | -0.18 liters | Standard Deviation 0.2 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 9 (n=251, 264) | -0.06 liters | Standard Deviation 0.14 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 27 (n=136,146) | -0.19 liters | Standard Deviation 0.2 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 6 (n=240, 218) | -0.10 liters | Standard Deviation 0.17 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 30 (n=136,147) | -0.20 liters | Standard Deviation 0.2 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 18 (n=227, 232) | -0.09 liters | Standard Deviation 0.15 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 33 (n=127,139) | -0.20 liters | Standard Deviation 0.21 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 1 (n=166, 175) | -0.14 liters | Standard Deviation 0.2 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 36 (n=105,126) | -0.23 liters | Standard Deviation 0.22 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 6 (n=262, 273) | -0.05 liters | Standard Deviation 0.14 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 39 (n=52, 64) | -0.21 liters | Standard Deviation 0.23 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 3 (n=161, 175) | -0.14 liters | Standard Deviation 0.18 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 39 (LOCF) (n=177, 187) | -0.22 liters | Standard Deviation 0.21 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 21 (n=218, 224) | -0.11 liters | Standard Deviation 0.16 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Follow Up Month 3 (n=115,102) | -0.20 liters | Standard Deviation 0.2 |
| Inhaled Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline (n=283, 281) | 3.51 liters | Standard Deviation 0.76 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Follow Up Month 3 (n=115,102) | -0.17 liters | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline (n=283, 281) | 3.47 liters | Standard Deviation 0.78 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 3 (n=277, 263) | -0.01 liters | Standard Deviation 0.12 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 6 (n=262, 273) | -0.03 liters | Standard Deviation 0.13 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 9 (n=251, 264) | -0.04 liters | Standard Deviation 0.13 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 12 (n=242, 259) | -004 liters | Standard Deviation 0.13 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 15 (n=236, 250) | -0.05 liters | Standard Deviation 0.15 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 18 (n=227, 232) | -0.06 liters | Standard Deviation 0.15 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 21 (n=218, 224) | -0.06 liters | Standard Deviation 0.15 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Month 24 (n=211, 219) | -0.08 liters | Standard Deviation 0.16 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 1 (n=242, 209) | -0.09 liters | Standard Deviation 0.16 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 3 (n=249, 225) | -0.09 liters | Standard Deviation 0.15 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 6 (n=240, 218) | -0.09 liters | Standard Deviation 0.16 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 1 (n=166, 175) | -0.10 liters | Standard Deviation 0.17 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 3 (n=161, 175) | -0.10 liters | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 6 (n=158, 170) | -0.11 liters | Standard Deviation 0.17 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 9 (n=151, 164) | -0.12 liters | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 12 (n=152,161) | -0.11 liters | Standard Deviation 0.16 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 15 (n=153,162) | -0.12 liters | Standard Deviation 0.17 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 18 (n=148,160) | -0.14 liters | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 21 (n=144,158) | -0.15 liters | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 24 (n=141,153) | -0.14 liters | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 27 (n=136,146) | -0.13 liters | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 30 (n=136,147) | -0.16 liters | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 33 (n=127,139) | -0.17 liters | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 36 (n=105,126) | -0.16 liters | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 39 (n=52, 64) | -0.17 liters | Standard Deviation 0.21 |
| Subcutaneous Insulin | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Extension Month 39 (LOCF) (n=177, 187) | -0.15 liters | Standard Deviation 0.19 |
Comparison: Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.041, -0.007]ANCOVA
Comparison: Month 6; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.04, -0.003]ANCOVA
Comparison: Month 9; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.038, 0.001]ANCOVA
Comparison: Month 12; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.058, -0.019]ANCOVA
Comparison: Month 15; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.065, -0.02]ANCOVA
Comparison: Month 18; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.043, 0.002]ANCOVA
Comparison: Month 21; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.066, -0.02]ANCOVA
Comparison: Month 24; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.058, -0.009]ANCOVA
Comparison: Follow-up Month 1; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.039, 0.009]ANCOVA
Comparison: Follow-up Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.027, 0.017]ANCOVA
Comparison: Follow-up Month 6; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.037, 0.012]ANCOVA
Comparison: Extension Month 1; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.076, -0.014]ANCOVA
Comparison: Extension Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.076, -0.013]ANCOVA
Comparison: Extension Month 6; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.071, -0.008]ANCOVA
Comparison: Extension Month 9; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.074, -0.008]ANCOVA
Comparison: Extension Month 12; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.088, -0.025]ANCOVA
Comparison: Extension Month 15; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.071, -0.007]ANCOVA
Comparison: Extension Month 18; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.079, -0.01]ANCOVA
Comparison: Extension Month 21; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.055, 0.016]ANCOVA
Comparison: Extension Month 24; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.079, -0.004]ANCOVA
Comparison: Extension Month 27; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.091, -0.019]ANCOVA
Comparison: Extension Month 30; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.081, -0.01]ANCOVA
Comparison: Extension Month 33; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.073, 0.002]ANCOVA
Comparison: Extension Month 36; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.121, -0.038]ANCOVA
Comparison: Extension Month 39; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.124, 0.003]ANCOVA
Comparison: Extension Month 39 (LOCF); Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.098, -0.033]ANCOVA
Comparison: Extension Follow Up Month 3; Treatment difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted (Primary Analysis Model) includes terms of Treatment, Baseline Pulmonary Function Test (PFT), Center, Age, Sex, and Height.90% CI: [-0.085, -0.004]ANCOVA
Primary
Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1)
Number of subjects with a post-baseline Forced Expiratory Volume in One Second (FEV1) decrease of ≥ 15 % \[(baseline observed value minus visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrent illness, a repeat FEV1 was performed.
Time frame: Month 3 through Extension Follow-up 3
Population: FAS FEV1; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 6 (n=158, 170) | 2 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 12 (n=242, 259) | 1 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 9 (n=151, 164) | 3 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 24 (n=211, 219) | 3 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 12 (n=152, 161) | 2 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 3 (n=277, 263) | 0 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 15 (n=153, 162) | 1 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 15 (n=236, 250) | 3 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 18 (n=148, 160) | 4 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 3 (n=249, 225) | 3 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 21 (n=144, 158) | 4 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 9 (n=251, 264) | 0 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 24 (n=141, 153) | 3 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 6 (n=240, 218) | 5 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 27 (n=136, 146) | 6 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 18 (n=227, 232) | 0 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 30 (n=136, 147) | 6 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 1 (n=166, 175) | 2 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 33 (n=127, 139) | 4 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 6 (n=262, 273) | 0 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 36 (n=105, 126) | 7 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 3 (n=161, 175) | 4 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 39 (n=52, 64) | 2 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 21 (n=218, 224) | 2 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Follow Up Month 3 (n=115, 102) | 5 participants |
| Inhaled Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 1 (n=242, 209) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Follow Up Month 3 (n=115, 102) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 3 (n=277, 263) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 6 (n=262, 273) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 9 (n=251, 264) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 12 (n=242, 259) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 15 (n=236, 250) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 18 (n=227, 232) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 21 (n=218, 224) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Month 24 (n=211, 219) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 1 (n=242, 209) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 3 (n=249, 225) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Follow-up Month 6 (n=240, 218) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 1 (n=166, 175) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 3 (n=161, 175) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 6 (n=158, 170) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 9 (n=151, 164) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 12 (n=152, 161) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 15 (n=153, 162) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 18 (n=148, 160) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 21 (n=144, 158) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 24 (n=141, 153) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 27 (n=136, 146) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 30 (n=136, 147) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 33 (n=127, 139) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 36 (n=105, 126) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) | Extension Month 39 (n=52, 64) | 1 participants |
Primary
Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco).
Number of subjects with a post-baseline Carbon Monoxide Diffusing Capacity (DLco) decrease of ≥ 20% \[(baseline observed value minus visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrent illness, a repeat DLco was performed.
Time frame: Month 3 through Extension Follow-up Month 3
Population: FAS FEV1; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 18 (n=227, 232) | 5 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 3 (n=161, 173) | 4 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 9 (n=250, 266) | 2 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 6 (n=158, 169) | 4 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 12 (n=152, 161) | 5 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 21 (n=218, 224) | 4 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 15 (n=143, 160) | 3 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 9 (n=151, 163) | 2 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 18 (n=148, 159) | 1 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 24 (n=208, 219) | 2 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 21 (n=144, 156) | 5 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 12 (n=241, 258) | 2 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 24 (n=140, 152) | 5 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Follow-up Month 1 (n=242, 208) | 3 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 27 (n=136, 144) | 4 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 6 (n=262, 273) | 1 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 30 (n=135, 146) | 4 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Follow-up Month 3 (n=247, 225) | 1 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 33 (n=127, 139) | 3 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 15 (n=235, 249) | 1 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 36 (n=105, 122) | 4 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Follow-up Month 6 (n=240, 218) | 1 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 39 (n=52, 64) | 3 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 3 (n=277, 264) | 0 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Follow Up Month 3 (n=115, 101) | 3 participants |
| Inhaled Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 1 (n=166, 175) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Follow Up Month 3 (n=115, 101) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 9 (n=151, 163) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 3 (n=277, 264) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 6 (n=262, 273) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 9 (n=250, 266) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 12 (n=241, 258) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 15 (n=235, 249) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 18 (n=227, 232) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 21 (n=218, 224) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Month 24 (n=208, 219) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Follow-up Month 1 (n=242, 208) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Follow-up Month 3 (n=247, 225) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Follow-up Month 6 (n=240, 218) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 1 (n=166, 175) | 0 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 3 (n=161, 173) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 12 (n=152, 161) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 15 (n=143, 160) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 18 (n=148, 159) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 21 (n=144, 156) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 24 (n=140, 152) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 27 (n=136, 144) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 30 (n=135, 146) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 33 (n=127, 139) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 36 (n=105, 122) | 7 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 39 (n=52, 64) | 1 participants |
| Subcutaneous Insulin | Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). | Extension Month 6 (n=158, 169) | 2 participants |
Secondary
Baseline Dyspnea Index (BDI)
Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI score range 0 (very severe impairment) to 4 (no impairment) scaled to a BDI focal score (0-12). Lower score indicates greater impairment.
Time frame: Week - 1
Population: FAS FEV1. Due to early termination of the study a limited set of analyses were undertaken and results of the Baseline Dyspnea Index were not summarized as planned.
Secondary
Change From Baseline Body Weight
Body weight: mean Baseline and change from Baseline in kilograms (kg). Change from baseline = mean body weight in kilograms (kg) at observation minus mean baseline body weight.
Time frame: Baseline through Extension Follow-up Month 3
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline Body Weight | Month 6 (n=259, 272) | 0.11 kilograms | Standard Deviation 2.89 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 3 (n=161, 175) | 1.73 kilograms | Standard Deviation 4.69 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 21 (n=220, 224) | 1.07 kilograms | Standard Deviation 4.22 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 6 (n=158, 170) | 1.67 kilograms | Standard Deviation 4.93 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 9 (n=251, 266) | 0.05 kilograms | Standard Deviation 3.28 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 9 (n=153, 164) | 1.61 kilograms | Standard Deviation 4.73 |
| Inhaled Insulin | Change From Baseline Body Weight | Week 8 (n=263, 262) | 0.46 kilograms | Standard Deviation 1.88 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 12 (n=152, 162) | 2.11 kilograms | Standard Deviation 4.95 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 12 (n=242, 259) | 0.37 kilograms | Standard Deviation 3.46 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 15 (n=153, 162) | 2.01 kilograms | Standard Deviation 5.06 |
| Inhaled Insulin | Change From Baseline Body Weight | Baseline (n=288, 286) | 75.12 kilograms | Standard Deviation 13.57 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 18 (n=149, 160) | 2.31 kilograms | Standard Deviation 5.5 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 15 (n=236, 250) | 0.44 kilograms | Standard Deviation 3.57 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 21 (n=144, 158) | 2.14 kilograms | Standard Deviation 5.63 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 3 (n=273, 269) | 0.13 kilograms | Standard Deviation 2.2 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 24 (n=141, 153) | 2.49 kilograms | Standard Deviation 5.98 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 18 (n=227, 233) | 0.57 kilograms | Standard Deviation 3.99 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 27 (n=136, 146) | 2.12 kilograms | Standard Deviation 5.87 |
| Inhaled Insulin | Change From Baseline Body Weight | Follow-up Month 3 (n=248, 225) | 1.50 kilograms | Standard Deviation 4.24 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 30 (n=136, 147) | 2.42 kilograms | Standard Deviation 6.25 |
| Inhaled Insulin | Change From Baseline Body Weight | Week 18 (n=248, 260) | 0.15 kilograms | Standard Deviation 2.6 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 33 (n=127, 139) | 2.30 kilograms | Standard Deviation 5.96 |
| Inhaled Insulin | Change From Baseline Body Weight | Month 24 (n=211, 220) | 0.99 kilograms | Standard Deviation 4.58 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 36 (n=105, 126) | 2.11 kilograms | Standard Deviation 6.24 |
| Inhaled Insulin | Change From Baseline Body Weight | Follow-up Month 6 (n=239, 219) | 1.68 kilograms | Standard Deviation 4.28 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 39 (n=52, 64) | 1.58 kilograms | Standard Deviation 7.9 |
| Inhaled Insulin | Change From Baseline Body Weight | Week 4 (n=257, 247) | 0.30 kilograms | Standard Deviation 1.39 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Follow-Up Month 3 (n=116, 103) | 2.49 kilograms | Standard Deviation 5.98 |
| Inhaled Insulin | Change From Baseline Body Weight | Extension Month 1 (n=166, 175) | 2.44 kilograms | Standard Deviation 6.98 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Follow-Up Month 3 (n=116, 103) | 4.09 kilograms | Standard Deviation 6.34 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Follow-up Month 3 (n=248, 225) | 2.31 kilograms | Standard Deviation 4.89 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Baseline (n=288, 286) | 73.72 kilograms | Standard Deviation 13.13 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Week 4 (n=257, 247) | 0.63 kilograms | Standard Deviation 3.01 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Week 8 (n=263, 262) | 0.67 kilograms | Standard Deviation 2 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 3 (n=273, 269) | 0.67 kilograms | Standard Deviation 2.35 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Week 18 (n=248, 260) | 1.00 kilograms | Standard Deviation 2.64 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 6 (n=259, 272) | 1.25 kilograms | Standard Deviation 3.08 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 9 (n=251, 266) | 1.41 kilograms | Standard Deviation 3.35 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 12 (n=242, 259) | 1.55 kilograms | Standard Deviation 3.59 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 15 (n=236, 250) | 1.84 kilograms | Standard Deviation 3.9 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 18 (n=227, 233) | 2.26 kilograms | Standard Deviation 4.3 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 21 (n=220, 224) | 2.35 kilograms | Standard Deviation 4.51 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Follow-up Month 6 (n=239, 219) | 2.17 kilograms | Standard Deviation 4.46 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 1 (n=166, 175) | 2.50 kilograms | Standard Deviation 4.93 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 3 (n=161, 175) | 3.08 kilograms | Standard Deviation 7.17 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 6 (n=158, 170) | 3.05 kilograms | Standard Deviation 4.75 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 9 (n=153, 164) | 3.17 kilograms | Standard Deviation 5.27 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 12 (n=152, 162) | 3.08 kilograms | Standard Deviation 4.93 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 15 (n=153, 162) | 3.16 kilograms | Standard Deviation 5.21 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 18 (n=149, 160) | 3.30 kilograms | Standard Deviation 5.82 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 21 (n=144, 158) | 3.72 kilograms | Standard Deviation 5.82 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 24 (n=141, 153) | 4.23 kilograms | Standard Deviation 5.7 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 27 (n=136, 146) | 3.96 kilograms | Standard Deviation 6.15 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 30 (n=136, 147) | 4.80 kilograms | Standard Deviation 8.38 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 33 (n=127, 139) | 5.28 kilograms | Standard Deviation 10.84 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 36 (n=105, 126) | 3.87 kilograms | Standard Deviation 6.25 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Extension Month 39 (n=52, 64) | 4.83 kilograms | Standard Deviation 6.75 |
| Subcutaneous Insulin | Change From Baseline Body Weight | Month 24 (n=211, 220) | 2.23 kilograms | Standard Deviation 4.58 |
Comparison: Month 3; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-0.846, -0.199]ANCOVA
Comparison: Month 6; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.541, -0.685]ANCOVA
Comparison: Month 9; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.836, -0.882]ANCOVA
Comparison: Month 12; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.702, -0.666]ANCOVA
Comparison: Month 15; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.984, -0.869]ANCOVA
Comparison: Month 18; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.35, -1.084]ANCOVA
Comparison: Month 21; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.95, -0.596]ANCOVA
Comparison: Month 24; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.792, -0.346]ANCOVA
Comparison: Follow-up Month 3; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.475, -0.096]ANCOVA
Comparison: Follow-up Month 6; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.114, 0.224]ANCOVA
Comparison: Extension Month 1; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.133, 1.025]ANCOVA
Comparison: Extension Month 3; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.438, -0.235]ANCOVA
Comparison: Extension Month 6; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.356, -0.568]ANCOVA
Comparison: Extension Month 9; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.316, -0.454]ANCOVA
Comparison: Extension Month 12; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.877, -0.034]ANCOVA
Comparison: Extension Month 15; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-1.97, -0.03]ANCOVA
Comparison: Extension Month 18; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.041, 0.121]ANCOVA
Comparison: Extension Month 21; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.77, -0.565]ANCOVA
Comparison: Extension Month 24; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-3.013, -0.73]ANCOVA
Comparison: Extension Month 27; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-3.084, -0.69]ANCOVA
Comparison: Extension Month 30; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-4.264, -1.324]ANCOVA
Comparison: Extension Month 33; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-5.088, -1.485]ANCOVA
Comparison: Extension Month 36; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.901, -0.071]ANCOVA
Comparison: Extension Month 39; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-5.382, -0.88]ANCOVA
Comparison: Extension Follow Up Month 3; Treatment-Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Body Weight, and Center.90% CI: [-2.918, -0.055]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose
Change from Baseline: mean of (value of fasting plasma glucose \[milligrams per deciliter (mg/dL)\] at observation minus Baseline value).
Time frame: Baseline through Extension Follow-up Month 3
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Follow-up Month 6 (n=159, 164) | 3.45 mg/dL | Standard Deviation 80.26 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 18 (n=148, 163) | -12.42 mg/dL | Standard Deviation 86.69 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 21 (n=216, 230) | -26.77 mg/dL | Standard Deviation 88.96 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 21 (n=152, 157) | -24.75 mg/dL | Standard Deviation 87.29 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 1 (n=164, 171) | -25.52 mg/dL | Standard Deviation 90.15 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 24 (n=142, 148) | -20.46 mg/dL | Standard Deviation 86.45 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 12 (n=232, 256) | -24.25 mg/dL | Standard Deviation 87.53 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 27 (n=140, 148) | -14.91 mg/dL | Standard Deviation 78.42 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 3 (n=167, 172) | -25.02 mg/dL | Standard Deviation 87.75 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 30 (n=138, 147) | -17.16 mg/dL | Standard Deviation 86.47 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 24 (n=208, 222) | -18.36 mg/dL | Standard Deviation 92.92 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 33 (n=129, 141) | -22.77 mg/dL | Standard Deviation 94.77 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 6 (n=164, 177) | -13.47 mg/dL | Standard Deviation 80.85 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 36 (n=107, 132) | -20.00 mg/dL | Standard Deviation 81.03 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 18 (n=226, 236) | -24.13 mg/dL | Standard Deviation 86.44 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 39 (n=55, 64) | -38.47 mg/dL | Standard Deviation 95.17 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 9 (n=152, 170) | -16.19 mg/dL | Standard Deviation 94.12 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Follow-Up Month 3 (n=118, 105) | 1.97 mg/dL | Standard Deviation 95.39 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Follow-up Month 3 (n=2, 2) | -43.50 mg/dL | Standard Deviation 85.09 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Baseline (n=286, 286) | 171.24 mg/dL | Standard Deviation 63.2 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 12 (n=155, 167) | -22.53 mg/dL | Standard Deviation 83.01 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=263, 250) | -26.04 mg/dL | Standard Deviation 84.79 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 15 (n=230, 251) | -34.75 mg/dL | Standard Deviation 83.72 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 3 (n=267, 276) | -21.84 mg/dL | Standard Deviation 85.26 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 15 (n=148, 163) | -26.11 mg/dL | Standard Deviation 85.78 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 6 (n=258, 271) | -31.48 mg/dL | Standard Deviation 81.62 |
| Inhaled Insulin | Change From Baseline in Fasting Plasma Glucose | Month 9 (n=243, 262) | -25.34 mg/dL | Standard Deviation 86.24 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 6 (n=258, 271) | -6.29 mg/dL | Standard Deviation 83.81 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 9 (n=243, 262) | 1.28 mg/dL | Standard Deviation 96.32 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 12 (n=232, 256) | -4.95 mg/dL | Standard Deviation 85.96 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 15 (n=230, 251) | 5.96 mg/dL | Standard Deviation 89.39 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 18 (n=226, 236) | -8.13 mg/dL | Standard Deviation 88.83 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 21 (n=216, 230) | -11.62 mg/dL | Standard Deviation 82.98 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 24 (n=208, 222) | 1.25 mg/dL | Standard Deviation 84.87 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Follow-up Month 3 (n=2, 2) | 46.67 mg/dL | Standard Deviation 24.04 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Follow-up Month 6 (n=159, 164) | 1.46 mg/dL | Standard Deviation 85.49 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 1 (n=164, 171) | -2.72 mg/dL | Standard Deviation 91.27 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 3 (n=167, 172) | 0.43 mg/dL | Standard Deviation 84.55 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 6 (n=164, 177) | -12.56 mg/dL | Standard Deviation 86.93 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 9 (n=152, 170) | -4.46 mg/dL | Standard Deviation 88.86 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 12 (n=155, 167) | -5.15 mg/dL | Standard Deviation 81.38 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 15 (n=148, 163) | -10.64 mg/dL | Standard Deviation 86 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 18 (n=148, 163) | -2.32 mg/dL | Standard Deviation 84.41 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 21 (n=152, 157) | 4.86 mg/dL | Standard Deviation 89.31 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 24 (n=142, 148) | -10.36 mg/dL | Standard Deviation 93.08 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 27 (n=140, 148) | -2.86 mg/dL | Standard Deviation 91.97 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 30 (n=138, 147) | -3.77 mg/dL | Standard Deviation 86.15 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 33 (n=129, 141) | -12.12 mg/dL | Standard Deviation 88.26 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 36 (n=107, 132) | -2.49 mg/dL | Standard Deviation 86.06 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Month 39 (n=55, 64) | -1.57 mg/dL | Standard Deviation 78.47 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Extension Follow-Up Month 3 (n=118, 105) | 3.25 mg/dL | Standard Deviation 84.53 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Baseline (n=286, 286) | 170.06 mg/dL | Standard Deviation 55.2 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Week 6 (n=263, 250) | -14.02 mg/dL | Standard Deviation 80.13 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose | Month 3 (n=267, 276) | -6.15 mg/dL | Standard Deviation 79.08 |
Comparison: Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-25.24, -4.39]ANCOVA
Comparison: Month 6; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-35.16, -14.51]ANCOVA
Comparison: Month 9; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-37.56, -14.75]ANCOVA
Comparison: Month 12; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-30.56, -8.36]ANCOVA
Comparison: Month 15; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-50.93, -29]ANCOVA
Comparison: Month 18; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-27.65, -4.51]ANCOVA
Comparison: Month 21; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-24.69, -2.39]ANCOVA
Comparison: Month 24; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-30.88, -6.84]ANCOVA
Comparison: Follow-up Month 6; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin.Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-9.83, 16.96]ANCOVA
Comparison: Extension Month 1; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-31.32, -4.27]ANCOVA
Comparison: Extension Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-33.44, -7.99]ANCOVA
Comparison: Extension Month 6; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-11.06, 14.66]ANCOVA
Comparison: Extension Month 9; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-23.61, 6.17]ANCOVA
Comparison: Extension Month 12; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-29.28, -3.4]ANCOVA
Comparison: Extension Month 15; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-26.6, 0.63]ANCOVA
Comparison: Extension Month 18; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-24.39, 3.94]ANCOVA
Comparison: Extension Month 21; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-43.19, -14.09]ANCOVA
Comparison: Extension Month 24; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-23.69, 5.71]ANCOVA
Comparison: Extension Month 27; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-24.04, 5]ANCOVA
Comparison: Extension Month 30; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-24.71, 3.92]ANCOVA
Comparison: Extension Month 33; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-21.42, 9.09]ANCOVA
Comparison: Extension Month 36; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-20.98, 10.21]ANCOVA
Comparison: Extension Month 39; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-38.43, 7.26]ANCOVA
Comparison: Extension Follow Up Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline Fasting Plasma Glucose, and Center.90% CI: [-15.79, 21.46]ANCOVA
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Change from Baseline: mean of (value of Glycosylated Hemoglobin \[HbA1c\] at observation minus Baseline value).
Time frame: Baseline through Extension Follow-up Month 3
Population: FAS HbA1c: received at least 1 dose of study treatment, had baseline HbA1c and at least 1 post-baseline HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 3 (n=170, 177) | 0.12 percent | Standard Deviation 0.95 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 6 (n=263, 274) | -0.21 percent | Standard Deviation 0.8 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 6 (n=166, 178) | 0.21 percent | Standard Deviation 0.99 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 18 (n=231, 237) | -0.11 percent | Standard Deviation 0.88 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 9 (n=159, 171) | 0.26 percent | Standard Deviation 1 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline (n=288, 286) | 7.41 percent | Standard Deviation 1.06 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 12 (n=158, 169) | 0.39 percent | Standard Deviation 0.98 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 21 (n=223, 231) | -0.05 percent | Standard Deviation 0.92 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 15 (n=156, 167) | 0.40 percent | Standard Deviation 1.05 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 9 (n=253, 266) | -0.10 percent | Standard Deviation 0.84 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 18 (n=153, 166) | 0.32 percent | Standard Deviation 0.94 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 24 (n=214, 225) | 0.05 percent | Standard Deviation 0.91 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 21 (n=154, 161) | 0.27 percent | Standard Deviation 0.99 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 3 (n=276, 280) | -0.36 percent | Standard Deviation 0.78 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 24 (n=149, 154) | 0.29 percent | Standard Deviation 0.89 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Follow-up Month 3 (n=205, 195) | -0.13 percent | Standard Deviation 0.87 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 27 (n=141, 151) | 0.33 percent | Standard Deviation 0.97 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 12 (n=240, 262) | -0.04 percent | Standard Deviation 0.87 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 30 (n=140, 150) | 0.33 percent | Standard Deviation 0.91 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Follow-up Month 6 (n=219, 221) | -0.10 percent | Standard Deviation 0.87 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 6 (n=269, 256) | -0.40 percent | Standard Deviation 0.61 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 36 (n=108, 132) | 0.30 percent | Standard Deviation 0.99 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 1 (n=171, 177) | -0.09 percent | Standard Deviation 0.9 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 39 (n=55, 66) | 0.30 percent | Standard Deviation 0.94 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 15 (n=236, 253) | -0.12 percent | Standard Deviation 0.85 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Follow-Up Month 3 (n=120, 107) | 0.14 percent | Standard Deviation 1 |
| Inhaled Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 33 (n=131, 143) | 0.40 percent | Standard Deviation 0.94 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Follow-Up Month 3 (n=120, 107) | 0.12 percent | Standard Deviation 1 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline (n=288, 286) | 7.46 percent | Standard Deviation 1.06 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 6 (n=269, 256) | -0.43 percent | Standard Deviation 0.61 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 3 (n=276, 280) | -0.41 percent | Standard Deviation 0.73 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 6 (n=263, 274) | -0.36 percent | Standard Deviation 0.81 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 9 (n=253, 266) | -0.23 percent | Standard Deviation 0.81 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 12 (n=240, 262) | -0.32 percent | Standard Deviation 0.82 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 15 (n=236, 253) | -0.29 percent | Standard Deviation 0.9 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 18 (n=231, 237) | -0.30 percent | Standard Deviation 0.89 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 21 (n=223, 231) | -0.25 percent | Standard Deviation 0.92 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Month 24 (n=214, 225) | -0.27 percent | Standard Deviation 0.83 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Follow-up Month 3 (n=205, 195) | -0.22 percent | Standard Deviation 0.83 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Follow-up Month 6 (n=219, 221) | -0.14 percent | Standard Deviation 0.87 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 1 (n=171, 177) | -0.23 percent | Standard Deviation 0.85 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 3 (n=170, 177) | -0.17 percent | Standard Deviation 0.91 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 6 (n=166, 178) | -0.19 percent | Standard Deviation 0.86 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 9 (n=159, 171) | -0.06 percent | Standard Deviation 0.94 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 12 (n=158, 169) | 0.08 percent | Standard Deviation 0.87 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 15 (n=156, 167) | 0.17 percent | Standard Deviation 0.85 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 18 (n=153, 166) | 0.05 percent | Standard Deviation 0.86 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 21 (n=154, 161) | 0.00 percent | Standard Deviation 0.88 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 24 (n=149, 154) | 0.06 percent | Standard Deviation 0.91 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 27 (n=141, 151) | 0.10 percent | Standard Deviation 0.92 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 30 (n=140, 150) | -0.01 percent | Standard Deviation 0.89 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 33 (n=131, 143) | -0.08 percent | Standard Deviation 0.92 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 36 (n=108, 132) | -0.03 percent | Standard Deviation 0.99 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Extension Month 39 (n=55, 66) | -0.09 percent | Standard Deviation 1 |
Comparison: Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [-0.06, 0.122]ANCOVA
Comparison: Month 6; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.033, 0.239]ANCOVA
Comparison: Month 9; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0, 0.224]ANCOVA
Comparison: Month 12; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.141, 0.374]ANCOVA
Comparison: Month 15; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.04, 0.273]ANCOVA
Comparison: Month 18; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.065, 0.3]ANCOVA
Comparison: Month 21; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.06, 0.319]ANCOVA
Comparison: Month 24; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.19, 0.443]ANCOVA
Comparison: Follow-up Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [-0.037, 0.224]ANCOVA
Comparison: Follow-up Month 6; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [-0.103, 0.145]ANCOVA
Comparison: Extension Month 1; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [-0.023, 0.248]ANCOVA
Comparison: Extension Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.126, 0.419]ANCOVA
Comparison: Extension Month 6; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.219, 0.507]ANCOVA
Comparison: Extension Month 9; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.128, 0.428]ANCOVA
Comparison: Extension Month 12; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.144, 0.442]ANCOVA
Comparison: Extension Month 15; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.058, 0.369]ANCOVA
Comparison: Extension Month 18; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.101, 0.386]ANCOVA
Comparison: Extension Month 21; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.079, 0.376]ANCOVA
Comparison: Extension Month 24; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.079, 0.372]ANCOVA
Comparison: Extension Month 27; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.055, 0.368]ANCOVA
Comparison: Extension Month 30; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.18, 0.483]ANCOVA
Comparison: Extension Month 33; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.302, 0.622]ANCOVA
Comparison: Extension Month 36; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.221, 0.6]ANCOVA
Comparison: Extension Month 39; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [0.183, 0.718]ANCOVA
Comparison: Extension Follow Up Month 3; Treatment Difference: Inhaled Insulin - Subcutaneous Insulin. Adjusted model includes terms of Treatment, Baseline HbA1c, and Center.90% CI: [-0.174, 0.237]ANCOVA
Secondary
Cough Questionnaire
Subject completed cough questionnaire with reference to the past 4 weeks. Six question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (subcutaneous \[SC\] or inhaled), and productivity of cough; range 0 (no symptoms) to 4 (severe symptoms). Questionnaire was administered at Week 0 and then at subsequent visits only if cough was identified as an adverse event not explained by a concomitant condition, such as an upper respiratory tract infection.
Time frame: Week 0 and if indicated through Extension Follow up Month 3
Population: FAS. Due to early termination of the study a limited set of analyses were undertaken and results of the Cough Questionnaire were not summarized as planned.
Secondary
Forced Vital Capacity (FVC)
Forced Vital Capacity (FVC) measured in liters (L).
Time frame: Week -3 through Extension Follow-up Month 6 or End of Study
Population: FAS FEV1. Due to early termination of the study a limited set of analyses were undertaken and FVC results were not summarized as planned.
Secondary
Hypoglycemic Event Rates
A Hypoglycemic event was identified by characteristic symptoms of hypoglycemia with no blood glucose check with prompt resolution with food intake, subcutaneous glucagon, or intravenouus glucose; characteristic symptoms with blood glucose of 59 milligrams per deciliter (mg/dL) (3.2 mmol/L) or less with blood glucose check; or any glucose measurement of 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Subject months = elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject month of treatment.
Time frame: Month 1 through Extension Month 39
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Hypoglycemic Event Rates | Month 1 (n=288, 286) | 7.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 9 (n=165, 177) | 2.1 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 15 (n=236, 258) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 10 (n=165, 176) | 3.1 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 2 (n=282, 286) | 5.9 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 16 (n=236, 256) | 3.4 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 12 (n=160, 175) | 3.3 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 4 (n=273, 282) | 4.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 13 (n=158, 174) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 17 (n=235, 252) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 14 (n=156, 173) | 2.9 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 3 (n=279, 285) | 5.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 15 (n=156, 173) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 19 (n=232, 250) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 16 (n=156, 172) | 3.4 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 8 (n=257, 273) | 4.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 17 (n=156, 172) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 20 (n=227, 245) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 18 (n=156, 172) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 3 (n=172, 185) | 4.1 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 19 (n=155, 172) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 21 (n=226, 244) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 20 (n=155, 170) | 2.9 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 9 (n=254, 272) | 3.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 21 (n=155, 169) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 22 (n=226, 243) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 22 (n=155, 165) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 5 (n=266, 280) | 4.7 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 23 (n=224, 238) | 2.5 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 24 (n=152, 163) | 2.9 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 10 (n=249, 270) | 4.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 25 (n=150, 162) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 24 (n=222, 229) | 2.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 26 (n=149, 160) | 2.7 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 11 (n=162, 175) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 27 (n=147, 159) | 2.7 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 1 (n=177, 187) | 3.5 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 28 (n=146, 158) | 2.7 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 11 (n=245, 269) | 3.9 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 29 (n=145, 155) | 2.7 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 2 (n=177, 187) | 3.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 30 (n=143, 153) | 2.5 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 6 (n=263, 277) | 4.5 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 31 (n=141, 153) | 2.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 12 (n=243, 267) | 3.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 32 (n=138, 152) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 4 (n=169, 182) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 33 (n=136, 150) | 2.3 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 7 (n=259, 275) | 4.5 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 34 (n=131, 148) | 2.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 5 (n=169, 182) | 3.2 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 35 (n=122, 147) | 1.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 13 (n=239, 265) | 3.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 36 (n=113, 138) | 1.9 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 6 (n=168, 182) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 37 (n=88, 104) | 1.5 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 18 (n=233, 250) | 3.0 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 38 (n=66, 73) | 1.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 7 (n=167, 181) | 3.1 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 39 (n=53, 64) | 1.7 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Month 14 (n=237, 260) | 3.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Overall Comparative (n=288, 286) | 4.1 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 8 (n=167, 178) | 2.6 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Overall Extension (n=177, 187) | 2.8 total events/subject months |
| Inhaled Insulin | Hypoglycemic Event Rates | Extension Month 23 (n=152, 164) | 3.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Overall Extension (n=177, 187) | 2.4 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 18 (n=233, 250) | 3.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 3 (n=279, 285) | 5.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 4 (n=273, 282) | 4.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 5 (n=266, 280) | 4.4 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 6 (n=263, 277) | 4.2 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 7 (n=259, 275) | 4.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 2 (n=282, 286) | 5.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 8 (n=257, 273) | 3.8 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 9 (n=254, 272) | 3.7 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 10 (n=249, 270) | 3.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 11 (n=245, 269) | 3.4 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 12 (n=243, 267) | 3.8 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 13 (n=239, 265) | 3.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 14 (n=237, 260) | 3.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 15 (n=236, 258) | 3.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 16 (n=236, 256) | 3.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 17 (n=235, 252) | 3.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 19 (n=232, 250) | 3.0 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 20 (n=227, 245) | 3.2 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 21 (n=226, 244) | 3.0 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 22 (n=226, 243) | 3.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 23 (n=224, 238) | 2.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 24 (n=222, 229) | 2.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 1 (n=177, 187) | 2.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 2 (n=177, 187) | 2.7 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 3 (n=172, 185) | 2.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 4 (n=169, 182) | 2.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 5 (n=169, 182) | 2.8 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 6 (n=168, 182) | 2.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 7 (n=167, 181) | 2.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 8 (n=167, 178) | 2.8 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 9 (n=165, 177) | 2.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 10 (n=165, 176) | 2.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 11 (n=162, 175) | 2.2 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 12 (n=160, 175) | 2.5 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 13 (n=158, 174) | 2.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 14 (n=156, 173) | 2.7 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 15 (n=156, 173) | 2.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 16 (n=156, 172) | 2.4 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 17 (n=156, 172) | 2.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 18 (n=156, 172) | 2.2 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 19 (n=155, 172) | 2.6 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 20 (n=155, 170) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 21 (n=155, 169) | 2.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 22 (n=155, 165) | 2.2 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 23 (n=152, 164) | 2.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 24 (n=152, 163) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 25 (n=150, 162) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 26 (n=149, 160) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 27 (n=147, 159) | 1.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 28 (n=146, 158) | 2.3 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 29 (n=145, 155) | 2.0 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 30 (n=143, 153) | 1.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 31 (n=141, 153) | 2.2 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 32 (n=138, 152) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 33 (n=136, 150) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 34 (n=131, 148) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 35 (n=122, 147) | 2.1 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 36 (n=113, 138) | 2.4 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 37 (n=88, 104) | 2.0 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 38 (n=66, 73) | 1.7 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Extension Month 39 (n=53, 64) | 1.4 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Overall Comparative (n=288, 286) | 3.9 total events/subject months |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Month 1 (n=288, 286) | 6.3 total events/subject months |
Secondary
Insulin Antibodies
Median insulin antibodies at each visit measured in micro units per milliliter (microU/mL).
Time frame: Baseline through Extension Month 39
Population: FAS; (n)= number of subjects with analyzable data at observation: inhaled insulin/SC insulin, respectively. Insulin antibody levels increased in Exubera®-treated compared to control subjects; results are included to establish there were no safety consequences due to these elevations although this was not an originally specified protocol endpoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Insulin | Insulin Antibodies | Week 3 (n=262, 260) | 7.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 3 (n=271, 274) | 31.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 24 (n=146, 153) | 42.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Follow-up Month 6 (n=239, 223) | 22.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 24 (n=212, 224) | 67.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Follow-up Month 1 (n=234, 209) | 41.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Follow-up Month 3 (n=245, 226) | 28.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Baseline (n=284, 283) | 4.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Week 6 (n=267, 260) | 15.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Week 18 (n=263, 271) | 49.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 6 (n=254, 268) | 88.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 9 (n=244, 262) | 134.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 12 (n=234, 258) | 142.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 15 (n=230, 250) | 109.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 18 (n=226, 233) | 91.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Month 21 (n=216, 228) | 59.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 1 (n=164, 176) | 37.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 3 (165, 177) | 45.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 6 (n=162, 176) | 42.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 9 (n=154, 167) | 41.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 12 (n=155, 167) | 49.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 15 (n=149, 163) | 43.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 18 (n=149, 160) | 45.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 21 (n=151, 157) | 44.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 27 (n=138, 148) | 35.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 30 (n=139, 150) | 36.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 33 (n=129, 142) | 35.00 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 36 (n=104, 132) | 30.50 microU/mL |
| Inhaled Insulin | Insulin Antibodies | Extension Month 39 (n=54, 66) | 25.50 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 30 (n=139, 150) | 5.25 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Week 6 (n=267, 260) | 4.00 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 21 (n=216, 228) | 3.85 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 21 (n=151, 157) | 3.60 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Follow-up Month 6 (n=239, 223) | 4.40 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Follow-up Month 3 (n=245, 226) | 4.20 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 18 (n=149, 160) | 3.60 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 1 (n=164, 176) | 4.50 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 24 (n=212, 224) | 4.40 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 36 (n=104, 132) | 3.65 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Follow-up Month 1 (n=234, 209) | 4.20 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 3 (165, 177) | 4.40 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 24 (n=146, 153) | 4.40 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Baseline (n=284, 283) | 4.10 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 6 (n=162, 176) | 3.55 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Week 3 (n=262, 260) | 3.60 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 3 (n=271, 274) | 4.25 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 33 (n=129, 142) | 4.30 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Week 18 (n=263, 271) | 4.40 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 9 (n=154, 167) | 4.70 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 6 (n=254, 268) | 5.10 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 27 (n=138, 148) | 6.35 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 9 (n=244, 262) | 4.95 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 12 (n=155, 167) | 4.30 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 12 (n=234, 258) | 4.90 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 39 (n=54, 66) | 1.58 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 15 (n=230, 250) | 4.70 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Extension Month 15 (n=149, 163) | 4.50 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Month 18 (n=226, 233) | 4.40 microU/mL |
Secondary
Lipids
Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides measured as milligrams per deciliter (mg/dL).
Time frame: Week -4 through Month 24
Population: Full Analysis Set (FAS): received at least 1 dose of study treatment. Due to early termination of the study a limited set of analyses were undertaken and lipid results were not summarized as planned.
Secondary
Severe Hypoglycemic Event Rates
Severe hypoglycemic event = all 3 of the following criteria were met: subject unable to treat self, exhbited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness); and blood glucose measurement was ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, subcutaneous glucagon, or i.v. glucose. Subject months = elapsed number of months subject was in study in each time interval. Crude event rate = total events divided by subject months \* 100.
Time frame: Month 1 through Extension Month 39
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 31 (n=141, 153) | 3.1 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 18 (n=233, 250) | 2.6 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 2 (n=282, 286) | 7.9 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 19 (n=232, 250) | 0.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 20 (n=227, 245) | 0.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 11 (n=162, 175) | 2.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 21 (n=226, 244) | 1.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 32 (n=138, 152) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 22 (n=226, 243) | 0.9 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 4 (n=273, 282) | 3.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 23 (n=224, 238) | 0.9 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 15 (n=156, 173) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 24 (n=222, 239) | 0.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 1 (n=177, 187) | 3.9 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 5 (n=266, 280) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 2 (n=177, 187) | 4.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 33 (n=136, 150) | 2.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 3 (n=172, 185) | 4.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 4 (n=169, 182) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 6 (n=263, 277) | 3.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 6 (n=168, 182) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 7 (n=167, 181) | 0.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 18 (n=156, 172) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 8 (n=167, 178) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 7 (n=259, 275) | 2.3 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 9 (n=165, 177) | 2.1 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 10 (n=165, 176) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 34 (n=131, 148) | 0.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 12 (n=160, 175) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 8 (n=257, 273) | 2.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 13 (n=158, 174) | 0.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 14 (n=156, 173) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 22 (n=155, 165) | 2.1 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 16 (n=156, 172) | 0.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 9 (n=254, 272) | 4.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 17 (n=156, 172) | 0.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 35 (n=122, 147) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 10 (n=249, 270) | 0.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 19 (n=155, 172) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 29 (n=145, 155) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 20 (n=155, 170) | 2.1 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 11 (n=245, 269) | 2.1 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 21 (n=155, 169) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 36 (n=113, 138) | 1.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 12 (n=243, 267) | 2.5 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 23 (n=152, 164) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 30 (n=143, 153) | 0.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 24 (n=152, 163) | 0.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 13 (n=239, 265) | 1.3 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 25 (n=150, 162) | 1.5 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 37 (n=88, 104) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 26 (n=149, 160) | 2.2 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 14 (n=237, 260) | 1.3 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 27 (n=147, 159) | 0.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 5 (n=169, 182) | 2.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 28 (n=146, 158) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 15 (n=236, 258) | 1.7 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 38 (n=66, 73) | 0.0 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 16 (n=236, 256) | 2.6 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Extension Month 39 (n=53, 64) | 0.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 1 (n=288, 286) | 10.2 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Overall Comparative (n=288, 286) | 2.8 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 17 (n=235, 252) | 3.9 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Overall Extension (n=177, 187) | 1.4 events / subject months * 100 |
| Inhaled Insulin | Severe Hypoglycemic Event Rates | Month 3 (n=279, 285) | 6.5 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Overall Extension (n=177, 187) | 3.3 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 19 (n=232, 250) | 2.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 24 (n=222, 239) | 2.6 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 3 (n=172, 185) | 2.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 4 (n=169, 182) | 1.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 6 (n=168, 182) | 3.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 9 (n=165, 177) | 4.9 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 10 (n=165, 176) | 3.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 13 (n=158, 174) | 1.8 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 14 (n=156, 173) | 3.1 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 30 (n=143, 153) | 0.7 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 31 (n=141, 153) | 0.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 32 (n=138, 152) | 1.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 33 (n=136, 150) | 1.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 34 (n=131, 148) | 1.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 35 (n=122, 147) | 5.9 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 36 (n=113, 138) | 0.9 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 37 (n=88, 104) | 3.8 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 1 (n=288, 286) | 9.1 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 2 (n=282, 286) | 7.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 3 (n=279, 285) | 6.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 4 (n=273, 282) | 4.3 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 5 (n=266, 280) | 4.3 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 6 (n=263, 277) | 6.5 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 7 (n=259, 275) | 4.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 8 (n=257, 273) | 4.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 9 (n=254, 272) | 5.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 10 (n=249, 270) | 3.3 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 11 (n=245, 269) | 3.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 12 (n=243, 267) | 3.8 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 13 (n=239, 265) | 2.7 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 14 (n=237, 260) | 3.5 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 15 (n=236, 258) | 3.1 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 16 (n=236, 256) | 2.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 17 (n=235, 252) | 1.6 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 18 (n=233, 250) | 5.6 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 20 (n=227, 245) | 4.9 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 21 (n=226, 244) | 2.9 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 22 (n=226, 243) | 2.1 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Month 23 (n=224, 238) | 2.6 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 1 (n=177, 187) | 1.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 2 (n=177, 187) | 7.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 5 (n=169, 182) | 4.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 7 (n=167, 181) | 2.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 8 (n=167, 178) | 2.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 11 (n=162, 175) | 1.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 12 (n=160, 175) | 4.3 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 15 (n=156, 173) | 11.1 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 16 (n=156, 172) | 13.7 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 17 (n=156, 172) | 5.6 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 18 (n=156, 172) | 7.5 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 19 (n=155, 172) | 6.9 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 20 (n=155, 170) | 2.5 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 21 (n=155, 169) | 3.8 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 22 (n=155, 165) | 1.3 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 23 (n=152, 164) | 3.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 24 (n=152, 163) | 3.2 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 25 (n=150, 162) | 0.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 26 (n=149, 160) | 0.7 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 27 (n=147, 159) | 0.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 28 (n=146, 158) | 3.4 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 29 (n=145, 155) | 0.7 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 38 (n=66, 73) | 0.0 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Extension Month 39 (n=53, 64) | 1.7 events / subject months * 100 |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Overall Comparative (n=288, 286) | 4.1 events / subject months * 100 |
Secondary
Total Daily Long-Acting Insulin Dose Adjusted for Body Weight
Total daily dose of long-acting insulin adjusted for body weight (units per kilogram \[kg\]). Long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups.
Time frame: Month 3 through Extension Month 39
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 6 (n=166, 179) | 0.43 units/kg | Standard Deviation 0.24 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 27 (n=142, 153) | 0.43 units/kg | Standard Deviation 0.24 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 30 (n=141, 148) | 0.42 units/kg | Standard Deviation 0.26 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 3 (n=280, 285) | 0.41 units/kg | Standard Deviation 0.22 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 6 (n=271, 280) | 0.41 units/kg | Standard Deviation 0.23 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month9 (n=256, 269) | 0.41 units/kg | Standard Deviation 0.23 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 12 (n=243, 262) | 0.41 units/kg | Standard Deviation 0.24 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 15 (n=237, 255) | 0.42 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 18 (n=234, 242) | 0.42 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 21 (n=224, 233) | 0.42 units/kg | Standard Deviation 0.26 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 24 (n=218, 229) | 0.43 units/kg | Standard Deviation 0.27 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 1 (n=171, 178) | 0.45 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 3 (n=170, 177) | 0.44 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 9 (n=160, 174) | 0.44 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 12 (n=159, 169) | 0.44 units/kg | Standard Deviation 0.24 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 15 (n=156, 164) | 0.44 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 18 (n=152, 166) | 0.44 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 21 (n=154, 165) | 0.44 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 24 (n=150, 153) | 0.44 units/kg | Standard Deviation 0.26 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 33 (n=133, 144) | 0.42 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 36 (n=113, 136) | 0.40 units/kg | Standard Deviation 0.25 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 39 (n=57, 67) | 0.39 units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 1 (n=171, 178) | 0.49 units/kg | Standard Deviation 0.27 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 6 (n=166, 179) | 0.48 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 33 (n=133, 144) | 0.48 units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 27 (n=142, 153) | 0.49 units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 3 (n=170, 177) | 0.49 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 21 (n=154, 165) | 0.48 units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 3 (n=280, 285) | 0.48 units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 9 (n=160, 174) | 0.49 units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 6 (n=271, 280) | 0.49 units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 39 (n=57, 67) | 0.45 units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month9 (n=256, 269) | 0.49 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 12 (n=159, 169) | 0.47 units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 12 (n=243, 262) | 0.49 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 30 (n=141, 148) | 0.49 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 15 (n=237, 255) | 0.49 units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 15 (n=156, 164) | 0.49 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 18 (n=234, 242) | 0.50 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 36 (n=113, 136) | 0.46 units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 21 (n=224, 233) | 0.51 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 24 (n=150, 153) | 0.49 units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Month 24 (n=218, 229) | 0.50 units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose Adjusted for Body Weight | Extension Month 18 (n=152, 166) | 0.48 units/kg | Standard Deviation 0.24 |
Secondary
Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight)
Total Daily Long-Acting Insulin Dose Unadjusted for Body Weight; long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups.
Time frame: Month 3 through Extension Month 39
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 27 (n=142, 153) | 31.25 units | Standard Deviation 19.01 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 30 (n=141, 148) | 31.06 units | Standard Deviation 19.73 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 33 (n=133, 144) | 30.71 units | Standard Deviation 19.06 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 36 (n=113, 136) | 29.62 units | Standard Deviation 19.06 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 39 (n=57, 67) | 29.07 units | Standard Deviation 16.59 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 3 (n=280, 285) | 30.52 units | Standard Deviation 16 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 6 (n=271, 280) | 30.57 units | Standard Deviation 16.48 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 9 (n=256, 269) | 30.69 units | Standard Deviation 16.53 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 12 (n=243, 262) | 30.65 units | Standard Deviation 17.29 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 15 (n=237, 255) | 30.99 units | Standard Deviation 17.83 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 18 (n=234, 242) | 30.97 units | Standard Deviation 17.86 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 21 (n=224, 233) | 31.30 units | Standard Deviation 18.53 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 24 (n=218, 229) | 31.82 units | Standard Deviation 19.36 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 1 (n=171, 178) | 32.84 units | Standard Deviation 18.9 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 3 (n=170, 177) | 32.45 units | Standard Deviation 18.91 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 6 (n=166, 179) | 31.96 units | Standard Deviation 18.36 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 9 (n=160, 174) | 32.73 units | Standard Deviation 19.24 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 12 (n=159, 169) | 32.29 units | Standard Deviation 19.12 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 15 (n=156, 164) | 32.02 units | Standard Deviation 18.61 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 18 (n=152, 166) | 32.37 units | Standard Deviation 18.62 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 21 (n=154, 165) | 31.83 units | Standard Deviation 19.05 |
| Inhaled Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 24 (n=150, 153) | 31.99 units | Standard Deviation 19.59 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 21 (n=154, 165) | 35.14 units | Standard Deviation 17.24 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 27 (n=142, 153) | 35.58 units | Standard Deviation 18.42 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 21 (n=224, 233) | 36.75 units | Standard Deviation 17.76 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 30 (n=141, 148) | 35.34 units | Standard Deviation 18.73 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 9 (n=160, 174) | 35.22 units | Standard Deviation 17.41 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 33 (n=133, 144) | 34.83 units | Standard Deviation 17.47 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 24 (n=218, 229) | 36.21 units | Standard Deviation 18.02 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 36 (n=113, 136) | 33.58 units | Standard Deviation 15.64 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 18 (n=152, 166) | 34.88 units | Standard Deviation 17.44 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 39 (n=57, 67) | 33.63 units | Standard Deviation 19.79 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 1 (n=171, 178) | 35.67 units | Standard Deviation 18.72 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 3 (n=280, 285) | 34.97 units | Standard Deviation 17.38 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 24 (n=150, 153) | 35.61 units | Standard Deviation 18.34 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 6 (n=271, 280) | 35.37 units | Standard Deviation 17.72 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 3 (n=170, 177) | 35.10 units | Standard Deviation 18.07 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 9 (n=256, 269) | 35.35 units | Standard Deviation 18.06 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 15 (n=156, 164) | 35.52 units | Standard Deviation 18.37 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 12 (n=243, 262) | 35.42 units | Standard Deviation 18 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 6 (n=166, 179) | 34.75 units | Standard Deviation 17.55 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 15 (n=237, 255) | 35.75 units | Standard Deviation 17.86 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 12 (n=159, 169) | 33.82 units | Standard Deviation 15.65 |
| Subcutaneous Insulin | Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) | Month 18 (n=234, 242) | 36.35 units | Standard Deviation 18.13 |
Secondary
Total Daily Short-Acting Insulin Dose Adjusted for Body Weight
Total Daily Short-Acting Insulin Dose adjusted for body weight (milligrams \[mg\] or units divided by kilograms \[kg\]). 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: Month 3 through Extension Month 39
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 9 (n=160, 174) | 0.19 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 18 (n=234, 241) | 0.18 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 12 (n=159, 169) | 0.20 mg/kg, units/kg | Standard Deviation 0.13 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 6 (n=271, 281) | 0.15 mg/kg, units/kg | Standard Deviation 0.08 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 15 (n=156, 167) | 0.19 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 21 (n=224, 235) | 0.19 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 18 (n=153, 167) | 0.19 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 12 (n=243, 266) | 0.17 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 21 (n=154, 166) | 0.19 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 24 (n=219, 232) | 0.19 mg/kg, units/kg | Standard Deviation 0.12 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 24 (n=150, 156) | 0.20 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 3 (n=280, 285) | 0.14 mg/kg, units/kg | Standard Deviation 0.07 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 27 (n=142, 153) | 0.20 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 3 (n=170, 178) | 0.17 mg/kg, units/kg | Standard Deviation 0.08 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 30 (n=141, 149) | 0.20 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 15 (n=237, 255) | 0.17 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 33 (n=133, 144) | 0.20 mg/kg, units/kg | Standard Deviation 0.12 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 6 (n=166, 179) | 0.18 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 36 (n=113, 136) | 0.21 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 9 (n=257, 271) | 0.16 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 39 (n=57, 67) | 0.23 mg/kg, units/kg | Standard Deviation 0.14 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 1 (n=170, 179) | 0.15 mg/kg, units/kg | Standard Deviation 0.08 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 39 (n=57, 67) | 0.39 mg/kg, units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 1 (n=170, 179) | 0.35 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 3 (n=280, 285) | 0.34 mg/kg, units/kg | Standard Deviation 0.19 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 6 (n=271, 281) | 0.34 mg/kg, units/kg | Standard Deviation 0.19 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 9 (n=257, 271) | 0.34 mg/kg, units/kg | Standard Deviation 0.18 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 12 (n=243, 266) | 0.34 mg/kg, units/kg | Standard Deviation 0.18 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 15 (n=237, 255) | 0.34 mg/kg, units/kg | Standard Deviation 0.19 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 18 (n=234, 241) | 0.34 mg/kg, units/kg | Standard Deviation 0.19 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 21 (n=224, 235) | 0.34 mg/kg, units/kg | Standard Deviation 0.2 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Month 24 (n=219, 232) | 0.34 mg/kg, units/kg | Standard Deviation 0.21 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 3 (n=170, 178) | 0.35 mg/kg, units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 6 (n=166, 179) | 0.34 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 9 (n=160, 174) | 0.35 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 12 (n=159, 169) | 0.34 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 15 (n=156, 167) | 0.35 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 18 (n=153, 167) | 0.35 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 21 (n=154, 166) | 0.35 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 24 (n=150, 156) | 0.36 mg/kg, units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 27 (n=142, 153) | 0.36 mg/kg, units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 30 (n=141, 149) | 0.37 mg/kg, units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 33 (n=133, 144) | 0.36 mg/kg, units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose Adjusted for Body Weight | Extension Month 36 (n=113, 136) | 0.36 mg/kg, units/kg | Standard Deviation 0.25 |
Secondary
Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight)
Total daily dose of short-acting insulin 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: Month 3 through Extension Month 39
Population: FAS HbA1c; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 24 (n=150, 156) | 14.48 mg, units | Standard Deviation 8.71 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 24 (n=219, 232) | 14.61 mg, units | Standard Deviation 9.14 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 1 (n=170, 179) | 11.49 mg, units | Standard Deviation 6.35 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 3 (n=170, 178) | 12.50 mg, units | Standard Deviation 6.88 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 6 (n=166, 179) | 13.64 mg, units | Standard Deviation 9.07 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 9 (n=160, 174) | 14.06 mg, units | Standard Deviation 9.33 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 12 (n=159, 169) | 14.74 mg, units | Standard Deviation 10.07 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 15 (n=156, 167) | 13.93 mg, units | Standard Deviation 8.38 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 3 (n=280, 285) | 10.45 mg, units | Standard Deviation 5.71 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 6 (n=271, 281) | 11.50 mg, units | Standard Deviation 6.73 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 9 (n=257, 271) | 11.97 mg, units | Standard Deviation 6.79 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 12 (n=243, 266) | 12.69 mg, units | Standard Deviation 6.96 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 15 (n=237, 255) | 13.12 mg, units | Standard Deviation 7.65 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 21 (n=224, 235) | 14.42 mg, units | Standard Deviation 8.64 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 18 (n=153, 167) | 13.97 mg, units | Standard Deviation 8.58 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 21 (n=154, 166) | 14.53 mg, units | Standard Deviation 8.8 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 18 (n=234, 241) | 13.60 mg, units | Standard Deviation 8.04 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 27 (n=142, 153) | 14.82 mg, units | Standard Deviation 8.7 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 30 (n=141, 149) | 14.92 mg, units | Standard Deviation 8.93 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 33 (n=133, 144) | 15.28 mg, units | Standard Deviation 9.72 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 36 (n=113, 136) | 15.72 mg, units | Standard Deviation 8.32 |
| Inhaled Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 39 (n=57, 67) | 17.92 mg, units | Standard Deviation 12.04 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 9 (n=257, 271) | 24.90 mg, units | Standard Deviation 14.54 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 18 (n=234, 241) | 25.20 mg, units | Standard Deviation 15.15 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 36 (n=113, 136) | 27.04 mg, units | Standard Deviation 19.65 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 24 (n=219, 232) | 25.23 mg, units | Standard Deviation 16.57 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 12 (n=243, 266) | 25.32 mg, units | Standard Deviation 14.35 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 1 (n=170, 179) | 25.84 mg, units | Standard Deviation 17.48 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 24 (n=150, 156) | 27.26 mg, units | Standard Deviation 19.48 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 3 (n=170, 178) | 25.94 mg, units | Standard Deviation 18.26 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 15 (n=237, 255) | 25.11 mg, units | Standard Deviation 14.83 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 6 (n=166, 179) | 25.39 mg, units | Standard Deviation 17.52 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 33 (n=133, 144) | 26.71 mg, units | Standard Deviation 18.67 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 9 (n=160, 174) | 26.19 mg, units | Standard Deviation 18 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 21 (n=224, 235) | 25.45 mg, units | Standard Deviation 15.41 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 12 (n=159, 169) | 25.49 mg, units | Standard Deviation 17.69 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 39 (n=57, 67) | 29.75 mg, units | Standard Deviation 19.68 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 15 (n=156, 167) | 25.80 mg, units | Standard Deviation 17.62 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 27 (n=142, 153) | 26.63 mg, units | Standard Deviation 17.82 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 18 (n=153, 167) | 26.04 mg, units | Standard Deviation 17.52 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 3 (n=280, 285) | 25.05 mg, units | Standard Deviation 14.73 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 30 (n=141, 149) | 27.22 mg, units | Standard Deviation 18.66 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Month 6 (n=271, 281) | 25.14 mg, units | Standard Deviation 14.72 |
| Subcutaneous Insulin | Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) | Extension Month 21 (n=154, 166) | 25.95 mg, units | Standard Deviation 17.04 |
Secondary
Total Lung Capacity (TLC)
Total Lung Capacity measured in liters (L).
Time frame: Week -3 through Extension Follow-up Month 6 or End of Study
Population: FAS FEV1. Due to early termination of the study a limited set of analyses were undertaken and TLC results were not summarized as planned.
Secondary
Transition Dyspnea Index (TDI)
Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI score range -3 (major deterioration) to +3 (major improvement); sum of all domains yields the TDI focal score (-9 to +9); lower score indicates greater deterioration. Compared to previous scoring to determine deterioration or improvement.
Time frame: Week 4 through ,Extension Follow-up Month 6 and every 6 months thereafter or end of study
Population: FAS FEV1. Due to early termination of the study a limited set of analyses were undertaken and results of the Transition Dyspnea Index were not summarized as planned.