Diabetes Mellitus
Conditions
Brief summary
This study is being done to find out the good and bad effects of inhaled insulin that is used by oral inhalation, to adult males and females with type 2 diabetes mellitus. The other name for this inhaled insulin is Exubera®. 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 A2171029 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
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus
Exclusion criteria
* COPD * Asthma * Smoking Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Month 3 in Forced Expiratory Volume in 1 Second (FEV1) | Month 3 through extension Month 60 | Change from Month 3: mean of (value of observed FEV1 \[forced expiratory volume in the first second of forced exhalation\] in liters \[L\] at treatment observation minus Month 3 value). |
| Change From Baseline in FEV1 | Baseline through extension follow up Month 3 | Change from baseline: mean of (value of observed FEV1 \[L\] at treatment observation minus baseline value). |
| Annual Rate of Change in FEV1 | Week -2 through extension follow up Month 3 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). |
| Summary of ≥ 15 % Decliners in FEV1 | Month 3 through extension follow up Month 3 | Number of subjects with a post-baseline FEV1 decrease of ≥ 15 % \[(baseline observed value - visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrrent illness, a repeat FEV1 was performed. |
| Annual Rate of Change in Carbon Monoxide Diffusion Capacity (DLco) | Week -2 through extension follow up Month 3 or end of study | Annual rate of change in DLco calculated as slope over time (visit) measured as milliliters per minute per millimeters of mercury per year (ml/min/mmHg/yr). |
| Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Baseline through extension follow up Month 3 | Change from baseline: mean of (value of observed DLco \[milliliters per minute per millimeters of mercury (ml/min/mmHg)\] at treatment observation minus baseline value). |
| Summary of ≥ 20 % Decliners in DLco | Month 3 through extension follow up Month 3 | Number of subjects with a post-baseline DLco decrease of ≥ 20 % \[(baseline observed value - visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrrent illness, a repeat DLco was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Month 3 through extension Month 36 | Total daily dose of short-acting insulin unadjusted for body weight. Short-acting insulin (milligrams \[mg\]) for the inhaled insulin treatment group was inhaled insulin; short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin. |
| Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Month 3 through extension Month 36 | Total daily dose of short-acting insulin adjusted for body weight. Short-acting insulin (mg) for the inhaled insulin treatment group was inhaled insulin (mg divided by kg); short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin (units divided by kg). |
| Lipid Panel: Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, and Triglycerides | Week -4 through Month 24 | Lipid values for total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides measured as milligrams per deciliter (mg/dL). |
| Hypoglycemic Event Rates | Month 1 through extension Month 36 | Hypoglycemic event rate; hypoglycemic event identified by characteristic symptoms of hypoglycemia with no blood glucose (BG) check with prompt resolution with food intake, SC glucagon, or intravenous (IV) glucose; characteristic symptoms with BG of 59 mg/dL (3.2 mmol/L) or less with or without symptoms. Crude event rate = total events divided by subject months (elapsed number of months a subject was in the study at each time interval). |
| Severe Hypoglycemic Event Rates | Month 1 through extension Month 36 | Severe hypoglycemic event rate; all 3 criteria were met: subject unable to treat self, exhibited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty awakening, suspected seizure, loss of consciousness); BG measurement ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, SC glucagon, or IV glucose. Crude event rate: total events divided by subject months multiplied by 100 (\[total events/subject months\]\*100). Subjects months: elapsed number of months subject was in study in each time interval. |
| Forced Vital Capacity (FVC) | Week -3 through extension follow up Month 3 or end of study | Forced Vital Capacity (FVC) measured in liters (L). |
| 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 3 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. |
| High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Baseline, M12, M24, Ext M6, Ext M18, Ext M36 | Number of subjects with Yes or No responses (within normal limits at specified time points = Yes or not within normal limits at specified time points = No) at observation when HRCT of thorax was within normal limits at baseline. |
| High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Baseline, M12, M24, Ext M6, Ext M18, Ext M36 | Number of subjects with Yes or No responses (within normal limits at specified time points = Yes or not within normal limits at specified time points = No) at observation when HRCT of thorax was not within normal limits at baseline. No response at observation further categorized as no significant change (NSC), more abnormal (\> Abn), or less abnormal (\< Abn). |
| Insulin Antibodies | Baseline through extension Month 36 | Observed values for insulin antibodies measured as micro units per milliliter (microU/mL). |
| Cough Questionnaire | Week 0 and if indicated through extension follow up Month 3 | Clinician administered 6 question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (SC or inhaled), and productivity of cough; range 0 (indicates no symptoms) to 4 (indicates severe symptoms). Questionnaire administered at Week 0 then if and only if, cough is identified as an adverse event not explained by a concomitant condition, such as an upper respiratory tract infection. |
| Total Lung Capacity (TLC) | Baseline through extension follow up Month 3 | Total Lung Capacity measured in liters (L). |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline through extension follow up Month 3 | Change from baseline: mean of (value of observed HbA1c \[%\] at treatment observation minus baseline value). |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline through extension follow up Month 3 | Change from baseline: mean of (value of observed FPG \[milligrams per deciliter (mg/dL)\] at treatment observation minus baseline value). |
| Change From Baseline in Body Weight | Baseline through extension follow up Month 3 | Change from baseline: mean of (value of observed body weight \[kilograms (kg)\] at treatment observation minus baseline value). |
| Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Month 3 through extension Month 36 | Total daily long-acting insulin dose unadjusted for body weight. Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine. |
| Total Daily Long-acting Insulin (Adjusted for Body Weight) | Month 3 through extension Month 36 | Total daily dose of long-acting insulin adjusted for body weight (units per kilogram \[kg\]). Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine. |
Countries
Brazil, Canada, Puerto Rico, United States
Participant flow
Pre-assignment details
At screening visit and during the 4-week run-in phase subjects received subcutaneous insulin regime of 2 to 3 daily doses (QD) of regular insulin-/short-acting insulin analog (lispro or aspart) and 1 or 2 doses QD of intermediate or long-acting insulin (neutral protamine hagedorn \[NPH\] insulin or Ultralente®) or insulin glargine QD at bedtime.
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Insulin (Exubera®) Pre-prandial inhalable short-acting insulin (INH) regime (packaged as 1 mg and 3 mg inhalation blister packs) plus a single bedtime dose or 2 daily doses of either Ultralene® or NPH insulin, or insulin glargine once daily (QD) at bedtime. | 316 |
| Subcutaneous Insulin Subcutaneous (SC) insulin: 2 to 3 daily doses of regular insulin or short-acting insulin analog (lispro or aspart) plus 1 or 2 daily doses of an intermediate to long-acting insulin (NPH insulin or Ultralene®), or insulin glargine QD at bedtime. | 311 |
| Total | 627 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 27 | 8 |
| Overall Study | Death | 1 | 3 |
| Overall Study | Discontinued in follow up period | 3 | 0 |
| Overall Study | Laboratory abnormality | 0 | 1 |
| Overall Study | Lack of Efficacy | 13 | 3 |
| Overall Study | Lost to Follow-up | 12 | 14 |
| Overall Study | Never received study treatment | 3 | 5 |
| Overall Study | Other | 22 | 24 |
| Overall Study | Withdrawal by Subject | 44 | 46 |
Baseline characteristics
| Characteristic | Inhaled Insulin (Exubera®) | Subcutaneous Insulin | Total |
|---|---|---|---|
| Age Continuous | 56.7 years STANDARD_DEVIATION 9.2 | 55.5 years STANDARD_DEVIATION 9.9 | 56.1 years STANDARD_DEVIATION 9.6 |
| Age, Customized Between 26 and 35 years | 2 participants | 7 participants | 9 participants |
| Age, Customized Between 36 and 45 years | 36 participants | 49 participants | 85 participants |
| Age, Customized Between 46 and 55 years | 100 participants | 93 participants | 193 participants |
| Age, Customized Between 56 and 65 years | 117 participants | 101 participants | 218 participants |
| Age, Customized Between 66 and 75 years | 61 participants | 61 participants | 122 participants |
| Sex: Female, Male Female | 111 Participants | 118 Participants | 229 Participants |
| Sex: Female, Male Male | 205 Participants | 193 Participants | 398 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 308 / 316 | 301 / 311 |
| serious Total, serious adverse events | 76 / 316 | 76 / 311 |
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 mercury per year (ml/min/mmHg/yr).
Time frame: Week -2 through extension follow up Month 3 or end of study
Population: FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of Annual rate of change in DLco were not summarized as planned. Cross reference outcome measure: change from baseline in Carbon Monoxide Diffusion Capacity (DLco).
Primary
Annual Rate of Change in 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 3 or end of study
Population: FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of 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 observed DLco \[milliliters per minute per millimeters of mercury (ml/min/mmHg)\] at treatment observation minus baseline value).
Time frame: Baseline through extension follow up Month 3
Population: FAS FEV1; extension M36 LOCF based on data in the extension phase only; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively. Cross reference outcome measure Annual rate of change in Carbon Monoxide Diffusion Capacity (DLco).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M21 (n=231, 231) | -0.89 ml/min/mmHg | Standard Deviation 1.98 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M6 (n=148, 157) | -1.48 ml/min/mmHg | Standard Deviation 1.87 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M12 (n=258, 263) | -0.72 ml/min/mmHg | Standard Deviation 1.86 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M9 (n=143, 155) | -1.15 ml/min/mmHg | Standard Deviation 2.31 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M24 (n=221, 223) | -0.74 ml/min/mmHg | Standard Deviation 2.1 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M12 (n=141, 155) | -1.49 ml/min/mmHg | Standard Deviation 2.22 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M3 (n=289, 290) | -0.57 ml/min/mmHg | Standard Deviation 1.6 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M15 (n=141, 142) | -1.49 ml/min/mmHg | Standard Deviation 2.25 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | FU M1 (n=247, 220) | -0.46 ml/min/mmHg | Standard Deviation 2.05 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M18 (n=132, 138) | -1.54 ml/min/mmHg | Standard Deviation 2.25 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M15 (n=246, 248) | -0.81 ml/min/mmHg | Standard Deviation 1.83 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M21 (n=129, 142) | -1.33 ml/min/mmHg | Standard Deviation 2.45 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | FU M3 (n=247, 231) | -0.58 ml/min/mmHg | Standard Deviation 2.07 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M24 (n=124, 130) | -1.39 ml/min/mmHg | Standard Deviation 2.27 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M9 (n=266, 272) | -0.67 ml/min/mmHg | Standard Deviation 1.78 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M27 (n=123, 124) | -1.35 ml/min/mmHg | Standard Deviation 2.48 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | FU M6 (n=241, 219) | -0.64 ml/min/mmHg | Standard Deviation 2.15 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M30 (n=124, 125) | -1.75 ml/min/mmHg | Standard Deviation 2.13 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M18 (n=237, 232) | -0.86 ml/min/mmHg | Standard Deviation 1.95 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M33 (n=98, 113) | -1.47 ml/min/mmHg | Standard Deviation 2.05 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M1 (n=159, 161) | -1.01 ml/min/mmHg | Standard Deviation 2.08 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M36 (n=52, 60) | -1.22 ml/min/mmHg | Standard Deviation 2.16 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M6 (n=278, 280) | -0.56 ml/min/mmHg | Standard Deviation 1.62 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M36 [LOCF] (n=171, 169) | -1.39 ml/min/mmHg | Standard Deviation 2.31 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M3 (n=157, 157) | -1.07 ml/min/mmHg | Standard Deviation 2.1 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext FU M3 (n=118, 114) | -1.12 ml/min/mmHg | Standard Deviation 2.15 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Baseline (n=308, 303) | 24.13 ml/min/mmHg | Standard Deviation 5.54 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext FU M3 (n=118, 114) | -1.69 ml/min/mmHg | Standard Deviation 2.56 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Baseline (n=308, 303) | 23.97 ml/min/mmHg | Standard Deviation 5.72 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M3 (n=289, 290) | -0.32 ml/min/mmHg | Standard Deviation 1.62 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M6 (n=278, 280) | -0.44 ml/min/mmHg | Standard Deviation 1.73 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M9 (n=266, 272) | -0.72 ml/min/mmHg | Standard Deviation 1.77 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M12 (n=258, 263) | -0.41 ml/min/mmHg | Standard Deviation 1.87 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M15 (n=246, 248) | -0.56 ml/min/mmHg | Standard Deviation 1.96 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M18 (n=237, 232) | -0.65 ml/min/mmHg | Standard Deviation 1.92 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M21 (n=231, 231) | -0.67 ml/min/mmHg | Standard Deviation 1.92 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | M24 (n=221, 223) | -0.81 ml/min/mmHg | Standard Deviation 2.06 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | FU M1 (n=247, 220) | -1.02 ml/min/mmHg | Standard Deviation 2.01 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | FU M3 (n=247, 231) | -0.90 ml/min/mmHg | Standard Deviation 2.15 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | FU M6 (n=241, 219) | -0.95 ml/min/mmHg | Standard Deviation 2.11 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M1 (n=159, 161) | -1.09 ml/min/mmHg | Standard Deviation 2.15 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M3 (n=157, 157) | -1.16 ml/min/mmHg | Standard Deviation 2.45 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M6 (n=148, 157) | -1.26 ml/min/mmHg | Standard Deviation 2.38 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M9 (n=143, 155) | -1.36 ml/min/mmHg | Standard Deviation 2.54 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M12 (n=141, 155) | -1.59 ml/min/mmHg | Standard Deviation 2.38 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M15 (n=141, 142) | -1.46 ml/min/mmHg | Standard Deviation 2.41 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M18 (n=132, 138) | -1.63 ml/min/mmHg | Standard Deviation 2.21 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M21 (n=129, 142) | -1.64 ml/min/mmHg | Standard Deviation 2.45 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M24 (n=124, 130) | -1.46 ml/min/mmHg | Standard Deviation 2.43 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M27 (n=123, 124) | -1.44 ml/min/mmHg | Standard Deviation 2.41 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M30 (n=124, 125) | -1.62 ml/min/mmHg | Standard Deviation 2.55 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M33 (n=98, 113) | -1.61 ml/min/mmHg | Standard Deviation 2.25 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M36 (n=52, 60) | -1.87 ml/min/mmHg | Standard Deviation 2.23 |
| Subcutaneous Insulin | Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) | Ext M36 [LOCF] (n=171, 169) | -1.77 ml/min/mmHg | Standard Deviation 2.46 |
Comparison: M390% CI: [-0.466, -0.037]
Comparison: M690% CI: [-0.323, 0.134]
Comparison: M990% CI: [-0.158, 0.325]
Comparison: M1290% CI: [-0.524, -0.009]
Comparison: M1590% CI: [-0.453, 0.091]
Comparison: M1890% CI: [-0.427, 0.145]
Comparison: M2190% CI: [-0.445, 0.134]
Comparison: M2490% CI: [-0.193, 0.431]
Comparison: FU M190% CI: [0.322, 0.911]
Comparison: FU M390% CI: [0.051, 0.657]
Comparison: FU M690% CI: [0.011, 0.626]
Comparison: Ext M190% CI: [-0.227, 0.5]
Comparison: Ext M390% CI: [-0.289, 0.485]
Comparison: Ext M690% CI: [-0.576, 0.172]
Comparison: Ext M990% CI: [-0.18, 0.669]
Comparison: Ext M1290% CI: [-0.284, 0.535]
Comparison: Ext M1590% CI: [-0.395, 0.441]
Comparison: Ext M1890% CI: [-0.262, 0.554]
Comparison: Ext M2190% CI: [-0.138, 0.78]
Comparison: Ext M2490% CI: [-0.419, 0.506]
Comparison: Ext M2790% CI: [-0.279, 0.659]
Comparison: Ext M3090% CI: [-0.579, 0.346]
Comparison: Ext M3390% CI: [-0.189, 0.714]
Comparison: Ext M3690% CI: [-0.37, 0.904]
Comparison: Ext M36 LOCF90% CI: [-0.003, 0.802]
Comparison: Ext FU M390% CI: [0.137, 1.102]
Primary
Change From Baseline in FEV1
Change from baseline: mean of (value of observed FEV1 \[L\] at treatment observation minus baseline value).
Time frame: Baseline through extension follow up Month 3
Population: FAS FEV1; extension Month 36 (M36) Last Observation Carried Forward (LOCF) based on data in the extension phase only; (n) = number of subjects with analyzable data at observation for inhaled insulin and SC insulin, respectively. Cross reference outcome measure: change from Month 3 in forced expiratory volume in 1 second.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M21 (n=232, 233) | -0.13 L | Standard Deviation 0.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M6 (n=148, 159) | -0.20 L | Standard Deviation 0.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M12 (n=259, 263) | -0.09 L | Standard Deviation 0.17 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M9 (n=144, 157) | -0.19 L | Standard Deviation 0.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M24 (n=223, 226) | -0.15 L | Standard Deviation 0.19 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M12 (n=144, 157) | -0.20 L | Standard Deviation 0.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Month 3 (M3) (n=290, 291) | -0.06 L | Standard Deviation 0.13 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M15 (n=141, 145) | -0.22 L | Standard Deviation 0.23 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Follow-up (FU) M1 (n=249, 221) | -0.14 L | Standard Deviation 0.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M18 (n=135, 139) | -0.22 L | Standard Deviation 0.23 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M15 (n=247, 250) | -0.12 L | Standard Deviation 0.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M21 (n=132, 143) | -0.23 L | Standard Deviation 0.24 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | FU M3 (n=248, 231) | -0.13 L | Standard Deviation 0.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M24 (n=125, 131) | -0.24 L | Standard Deviation 0.24 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M9 (n=266, 276) | -0.08 L | Standard Deviation 0.17 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M27 (n=124, 125) | -0.25 L | Standard Deviation 0.23 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | FU M6 (n=242, 220) | -0.12 L | Standard Deviation 0.2 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M30 (n=125, 126) | -0.24 L | Standard Deviation 0.22 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M18 (n=237, 236) | -0.12 L | Standard Deviation 0.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M33 (n=98, 113) | -0.24 L | Standard Deviation 0.24 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Extension (Ext) M1 (n=161, 163) | -0.16 L | Standard Deviation 0.2 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M36 (n=54, 60) | -0.25 L | Standard Deviation 0.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | M6 (n=281, 280) | -0.05 L | Standard Deviation 0.16 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M36 [LOCF] (n=171, 169) | -0.24 L | Standard Deviation 0.24 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext M3 (n=157, 158) | -0.19 L | Standard Deviation 0.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Ext FU M3 (n=119, 115) | -0.24 L | Standard Deviation 0.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in FEV1 | Baseline (n=311, 304) | 2.91 L | Standard Deviation 0.68 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext FU M3 (n=119, 115) | -0.25 L | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Baseline (n=311, 304) | 2.93 L | Standard Deviation 0.71 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Month 3 (M3) (n=290, 291) | -0.01 L | Standard Deviation 0.15 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M6 (n=281, 280) | -0.05 L | Standard Deviation 0.17 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M9 (n=266, 276) | -0.07 L | Standard Deviation 0.16 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M12 (n=259, 263) | -0.07 L | Standard Deviation 0.16 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M15 (n=247, 250) | -0.09 L | Standard Deviation 0.17 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M18 (n=237, 236) | -0.10 L | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M21 (n=232, 233) | -0.11 L | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | M24 (n=223, 226) | -0.13 L | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Follow-up (FU) M1 (n=249, 221) | -0.14 L | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | FU M3 (n=248, 231) | -0.14 L | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | FU M6 (n=242, 220) | -0.15 L | Standard Deviation 0.18 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Extension (Ext) M1 (n=161, 163) | -0.16 L | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M3 (n=157, 158) | -0.16 L | Standard Deviation 0.19 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M6 (n=148, 159) | -0.17 L | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M9 (n=144, 157) | -0.16 L | Standard Deviation 0.21 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M12 (n=144, 157) | -0.18 L | Standard Deviation 0.22 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M15 (n=141, 145) | -0.21 L | Standard Deviation 0.2 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M18 (n=135, 139) | -0.21 L | Standard Deviation 0.22 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M21 (n=132, 143) | -0.21 L | Standard Deviation 0.21 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M24 (n=125, 131) | -0.23 L | Standard Deviation 0.22 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M27 (n=124, 125) | -0.24 L | Standard Deviation 0.22 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M30 (n=125, 126) | -0.23 L | Standard Deviation 0.23 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M33 (n=98, 113) | -0.24 L | Standard Deviation 0.22 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M36 (n=54, 60) | -0.28 L | Standard Deviation 0.17 |
| Subcutaneous Insulin | Change From Baseline in FEV1 | Ext M36 [LOCF] (n=171, 169) | -0.24 L | Standard Deviation 0.21 |
Comparison: M390% CI: [-0.064, -0.026]
Comparison: M690% CI: [-0.025, 0.02]
Comparison: M990% CI: [-0.033, 0.013]
Comparison: M1290% CI: [-0.044, 0.004]
Comparison: M1590% CI: [-0.048, 0.003]
Comparison: M1890% CI: [-0.05, 0.004]
Comparison: M2190% CI: [-0.047, 0.007]
Comparison: M2490% CI: [-0.054, 0.002]
Comparison: FU M190% CI: [-0.021, 0.034]
Comparison: FU M390% CI: [-0.016, 0.044]
Comparison: FU M690% CI: [-0.002, 0.055]
Comparison: Ext M190% CI: [-0.04, 0.032]
Comparison: Ext M390% CI: [-0.07, 0.004]
Comparison: Ext M690% CI: [-0.077, -0.002]
Comparison: Ext M990% CI: [-0.075, 0.003]
Comparison: Ext M1290% CI: [-0.058, 0.022]
Comparison: Ext M1590% CI: [-0.034, 0.048]
Comparison: Ext M1890% CI: [-0.055, 0.033]
Comparison: Ext M2190% CI: [-0.058, 0.029]
Comparison: Ext M2490% CI: [-0.061, 0.03]
Comparison: Ext M2790% CI: [-0.044, 0.043]
Comparison: Ext M3090% CI: [-0.051, 0.04]
Comparison: Ext M3390% CI: [-0.042, 0.058]
Comparison: Ext M3690% CI: [-0.03, 0.077]
Comparison: Ext M36 LOCF90% CI: [-0.042, 0.035]
Comparison: Ext FU M390% CI: [-0.023, 0.062]
Primary
Change From Month 3 in Forced Expiratory Volume in 1 Second (FEV1)
Change from Month 3: mean of (value of observed FEV1 \[forced expiratory volume in the first second of forced exhalation\] in liters \[L\] at treatment observation minus Month 3 value).
Time frame: Month 3 through extension Month 60
Population: Full analysis set (FAS) FEV1: received at least 1 dose treatment, had baseline 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.
Primary
Summary of ≥ 15 % Decliners in FEV1
Number of subjects with a post-baseline FEV1 decrease of ≥ 15 % \[(baseline observed value - visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrrent illness, a repeat FEV1 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 (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M18 (n=237, 236) | 10 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M6 (n=148, 159) | 14 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M9 (n=266, 276) | 7 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M9 (n=144, 157) | 11 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M21 (n=232, 233) | 12 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M12 (n=144, 157) | 19 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M1 (n=161, 163) | 12 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M15 (n=141, 145) | 15 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M24 (n=223, 226) | 14 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M18 (n=135, 139) | 17 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M12 (n=259, 263) | 7 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M21 (n=132, 143) | 22 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | FU M1 (n=249, 221) | 11 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M24 (n=125, 131) | 22 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M6 (n=281, 280) | 3 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M27 (n=124, 125) | 18 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | FU M3 (n=248, 231) | 16 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M30 (n=125, 126) | 20 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M15 (n=247, 250) | 13 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M33 (n=98, 113) | 10 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | FU M6 (n=242, 220) | 13 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M36 (n=54, 60) | 5 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | M3 (n=290, 291) | 2 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext FU M3 (n=119, 115) | 14 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 15 % Decliners in FEV1 | Ext M3 (n=157, 158) | 12 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext FU M3 (n=119, 115) | 19 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M3 (n=290, 291) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M6 (n=281, 280) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M9 (n=266, 276) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M12 (n=259, 263) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M15 (n=247, 250) | 6 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M18 (n=237, 236) | 8 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M21 (n=232, 233) | 8 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | M24 (n=223, 226) | 13 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | FU M1 (n=249, 221) | 7 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | FU M3 (n=248, 231) | 15 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M1 (n=161, 163) | 6 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M3 (n=157, 158) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M6 (n=148, 159) | 8 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M9 (n=144, 157) | 10 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M12 (n=144, 157) | 13 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M15 (n=141, 145) | 11 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M18 (n=135, 139) | 18 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M21 (n=132, 143) | 11 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M24 (n=125, 131) | 16 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M27 (n=124, 125) | 14 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M30 (n=125, 126) | 18 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M33 (n=98, 113) | 12 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | Ext M36 (n=54, 60) | 6 participants |
| Subcutaneous Insulin | Summary of ≥ 15 % Decliners in FEV1 | FU M6 (n=242, 220) | 11 participants |
Primary
Summary of ≥ 20 % Decliners in DLco
Number of subjects with a post-baseline DLco decrease of ≥ 20 % \[(baseline observed value - visit observed value)/(baseline observed value) \* 100\]; in the absence of an obvious intercurrrent 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 (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M18(n=237, 232) | 2 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M6 (n=148, 157) | 4 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M9 (n=266, 272) | 0 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M9 (n=143, 155) | 4 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M24 (n=221, 223) | 4 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M12 (n=141, 155) | 8 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M21 (n=231, 231) | 0 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M15(n=141, 142) | 4 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | FU M1 (n=247, 220) | 2 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M18 (n=132, 138) | 6 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M12 (n=258, 263) | 4 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M21(n=129, 142) | 4 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | FU M3 (n=247, 231) | 3 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M24 (n=124, 130) | 5 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M6 (n=278, 280) | 1 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M27(n=123, 124) | 7 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | FU M6 (n=241, 219) | 5 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M30 (n=124, 125) | 7 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M15 (n=246, 248) | 1 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M33(n=98, 113) | 1 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M1 (n=159, 161) | 3 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M36 (n=52, 60) | 2 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | M3 (n=289, 290) | 0 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext FU M3 (n=118, 114) | 6 participants |
| Inhaled Insulin (Exubera®) | Summary of ≥ 20 % Decliners in DLco | Ext M3 (n=157, 157) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext FU M3 (n=118, 114) | 10 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M3 (n=289, 290) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M6 (n=278, 280) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M9 (n=266, 272) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M12 (n=258, 263) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M15 (n=246, 248) | 2 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M21 (n=231, 231) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M24 (n=221, 223) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | FU M1 (n=247, 220) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | FU M3 (n=247, 231) | 6 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | FU M6 (n=241, 219) | 5 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M1 (n=159, 161) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M3 (n=157, 157) | 8 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M6 (n=148, 157) | 6 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M9 (n=143, 155) | 7 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M12 (n=141, 155) | 9 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M15(n=141, 142) | 6 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M18 (n=132, 138) | 7 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M21(n=129, 142) | 8 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M24 (n=124, 130) | 7 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M27(n=123, 124) | 8 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M30 (n=124, 125) | 11 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M33(n=98, 113) | 4 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | Ext M36 (n=52, 60) | 3 participants |
| Subcutaneous Insulin | Summary of ≥ 20 % Decliners in DLco | M18(n=237, 232) | 5 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 study a limited set of analyses were undertaken and results of BDI were not summarized as planned.
Secondary
Change From Baseline in Body Weight
Change from baseline: mean of (value of observed body weight \[kilograms (kg)\] at treatment 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 (Exubera®) | Change From Baseline in Body Weight | Ext M1 (n=161, 162) | 2.87 kg | Standard Deviation 5.48 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | W18(n=280, 285) | 1.33 kg | Standard Deviation 3.13 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M3 (n=157, 157) | 2.83 kg | Standard Deviation 4.78 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M15(n=247, 249) | 1.88 kg | Standard Deviation 4.33 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M6 (n=148, 159) | 3.15 kg | Standard Deviation 5.7 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | W4 (n=280, 270) | 0.63 kg | Standard Deviation 2.11 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M9 (n=144, 156) | 2.95 kg | Standard Deviation 5.95 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M18(n=237, 235) | 1.79 kg | Standard Deviation 4.53 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M12 (n=144, 156) | 2.96 kg | Standard Deviation 6 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M6 (n=276, 277) | 1.15 kg | Standard Deviation 3.59 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M15 (n=142, 145) | 3.12 kg | Standard Deviation 5.91 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M21(n=232, 232) | 1.99 kg | Standard Deviation 4.56 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M18 (n=135, 139) | 3.33 kg | Standard Deviation 9.2 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M3 (n=288, 290) | 1.08 kg | Standard Deviation 2.75 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M21(n=132, 143) | 2.79 kg | Standard Deviation 6.9 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M24 (n=223, 226) | 2.04 kg | Standard Deviation 4.86 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M24 (n=126, 131) | 2.94 kg | Standard Deviation 6.98 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M9 (n=269, 274) | 1.50 kg | Standard Deviation 3.95 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M27(n=125, 125) | 2.99 kg | Standard Deviation 6.94 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | FU M3 (n=249, 231) | 2.32 kg | Standard Deviation 5.25 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M30 (n=125, 126) | 3.39 kg | Standard Deviation 6.43 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | W8 (n=289, 281) | 1.07 kg | Standard Deviation 2.41 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M33(n=99, 113) | 2.77 kg | Standard Deviation 6.33 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | FU M6 (n=243, 218) | 2.38 kg | Standard Deviation 5.34 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext M36 (n=54, 60) | 2.48 kg | Standard Deviation 6.61 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | M12 (n=259, 264) | 1.75 kg | Standard Deviation 4.29 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Ext FU M3 (n=119, 115) | 2.74 kg | Standard Deviation 6.9 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Body Weight | Baseline (n=314, 302) | 87.18 kg | Standard Deviation 14.75 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext FU M3 (n=119, 115) | 4.44 kg | Standard Deviation 6.87 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Baseline (n=314, 302) | 88.31 kg | Standard Deviation 15.5 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | W4 (n=280, 270) | 0.83 kg | Standard Deviation 1.86 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | W8 (n=289, 281) | 1.00 kg | Standard Deviation 2.31 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M3 (n=288, 290) | 1.13 kg | Standard Deviation 2.55 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | W18(n=280, 285) | 1.76 kg | Standard Deviation 3.03 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M6 (n=276, 277) | 1.89 kg | Standard Deviation 3.53 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M9 (n=269, 274) | 2.15 kg | Standard Deviation 3.9 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M12 (n=259, 264) | 2.37 kg | Standard Deviation 4.34 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M15(n=247, 249) | 2.62 kg | Standard Deviation 4.49 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M18(n=237, 235) | 2.93 kg | Standard Deviation 4.85 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M21(n=232, 232) | 3.04 kg | Standard Deviation 5.04 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | M24 (n=223, 226) | 3.36 kg | Standard Deviation 5.16 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | FU M3 (n=249, 231) | 3.63 kg | Standard Deviation 5.34 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | FU M6 (n=243, 218) | 4.09 kg | Standard Deviation 7.7 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M1 (n=161, 162) | 3.75 kg | Standard Deviation 5.58 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M3 (n=157, 157) | 4.14 kg | Standard Deviation 5.69 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M6 (n=148, 159) | 4.01 kg | Standard Deviation 6.07 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M9 (n=144, 156) | 3.89 kg | Standard Deviation 5.87 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M12 (n=144, 156) | 4.19 kg | Standard Deviation 6.12 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M15 (n=142, 145) | 4.54 kg | Standard Deviation 6.26 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M18 (n=135, 139) | 4.46 kg | Standard Deviation 6.12 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M21(n=132, 143) | 5.01 kg | Standard Deviation 8.37 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M24 (n=126, 131) | 4.57 kg | Standard Deviation 6.37 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M27(n=125, 125) | 5.58 kg | Standard Deviation 9.62 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M30 (n=125, 126) | 4.78 kg | Standard Deviation 6.96 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M33(n=99, 113) | 5.22 kg | Standard Deviation 7.21 |
| Subcutaneous Insulin | Change From Baseline in Body Weight | Ext M36 (n=54, 60) | 5.28 kg | Standard Deviation 7.09 |
Comparison: M390% CI: [-0.416, 0.299]
Comparison: M690% CI: [-1.224, -0.246]
Comparison: M1290% CI: [-1.251, -0.032]
Comparison: M2490% CI: [-2.12, -0.589]
Comparison: FU M390% CI: [-2.086, -0.52]
Comparison: FU M690% CI: [-2.539, -0.575]
Comparison: Ext M190% CI: [-1.898, 0.09]
Comparison: Ext M390% CI: [-2.225, -0.334]
Comparison: Ext M690% CI: [-1.909, 0.241]
Comparison: Ext M990% CI: [-2.08, 0.078]
Comparison: Ext M1290% CI: [-2.431, -0.2]
Comparison: Ext M1590% CI: [-2.661, -0.363]
Comparison: Ext M1890% CI: [-2.824, 0.198]
Comparison: Ext M2190% CI: [-3.891, -0.907]
Comparison: Ext M2490% CI: [-2.867, -0.265]
Comparison: Ext M2790% CI: [-4.439, -1.001]
Comparison: Ext M3090% CI: [-2.755, -0.047]
Comparison: Ext M3390% CI: [-3.781, -0.782]
Comparison: Ext M3690% CI: [-4.932, -0.599]
Comparison: Ext FU M390% CI: [-3.12, -0.153]
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline: mean of (value of observed FPG \[milligrams per deciliter (mg/dL)\] at treatment 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 (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M15(n=253, 255) | -21.37 mg/dL | Standard Deviation 54.53 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | W6 (n=282, 276) | -23.36 mg/dL | Standard Deviation 51.69 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M3 (n=294, 290) | -26.38 mg/dL | Standard Deviation 52.72 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M6 (n=281, 285) | -25.21 mg/dL | Standard Deviation 53.48 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M9 (n=267, 279) | -26.68 mg/dL | Standard Deviation 54.95 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M12 (n=260, 263) | -20.55 mg/dL | Standard Deviation 59.68 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline (n=315, 303) | 158.13 mg/dL | Standard Deviation 42.71 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M18(n=242, 238) | -24.52 mg/dL | Standard Deviation 54.5 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M21(n=232, 237) | -25.95 mg/dL | Standard Deviation 53.06 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | M24 (n=226, 232) | -24.02 mg/dL | Standard Deviation 54.45 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | FU M3 (n=5, 4) | -22.60 mg/dL | Standard Deviation 44.65 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | FU M6 (n=161, 156) | -2.85 mg/dL | Standard Deviation 66.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M1 (n=165, 162) | -17.91 mg/dL | Standard Deviation 60.96 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M3 (n=162, 159) | -18.16 mg/dL | Standard Deviation 66.59 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M6 (n=152, 161) | -15.65 mg/dL | Standard Deviation 67.18 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M9 (n=149, 155) | -13.99 mg/dL | Standard Deviation 61.68 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M12 (n=148, 155) | -12.53 mg/dL | Standard Deviation 72.25 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M15(n=143, 143) | -6.88 mg/dL | Standard Deviation 68.85 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M18 (n=136, 138) | -17.23 mg/dL | Standard Deviation 65.97 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M21(n=132, 144) | -12.86 mg/dL | Standard Deviation 63.98 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M24 (n=129, 136) | -14.45 mg/dL | Standard Deviation 61.65 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M27 (n=128, 129) | -21.68 mg/dL | Standard Deviation 58.35 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M30 (n=127, 130) | -11.80 mg/dL | Standard Deviation 62.82 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M33(n=103, 115) | -16.26 mg/dL | Standard Deviation 63.44 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M36 (n=55, 64) | -28.61 mg/dL | Standard Deviation 65.99 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext FU M3 (n=115, 118) | -2.87 mg/dL | Standard Deviation 81.19 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M21(n=132, 144) | -6.53 mg/dL | Standard Deviation 64.09 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline (n=315, 303) | 154.53 mg/dL | Standard Deviation 41.51 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M3 (n=162, 159) | -9.29 mg/dL | Standard Deviation 62.5 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | W6 (n=282, 276) | -12.55 mg/dL | Standard Deviation 50.46 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M36 (n=55, 64) | -13.35 mg/dL | Standard Deviation 53.97 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M3 (n=294, 290) | -12.77 mg/dL | Standard Deviation 54.93 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M6 (n=152, 161) | -4.34 mg/dL | Standard Deviation 61.96 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M6 (n=281, 285) | -9.05 mg/dL | Standard Deviation 68.42 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M24 (n=129, 136) | -3.47 mg/dL | Standard Deviation 68.57 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M9 (n=267, 279) | -10.41 mg/dL | Standard Deviation 56.42 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M9 (n=149, 155) | -6.06 mg/dL | Standard Deviation 60.86 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M12 (n=260, 263) | -7.60 mg/dL | Standard Deviation 60.03 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M33(n=103, 115) | -7.35 mg/dL | Standard Deviation 66.21 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M15(n=253, 255) | -8.82 mg/dL | Standard Deviation 55.57 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M12 (n=148, 155) | -4.98 mg/dL | Standard Deviation 62.92 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M18(n=242, 238) | -7.69 mg/dL | Standard Deviation 58.47 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M27 (n=128, 129) | -3.76 mg/dL | Standard Deviation 63.31 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M21(n=232, 237) | -13.14 mg/dL | Standard Deviation 54.66 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M15(n=143, 143) | -4.23 mg/dL | Standard Deviation 65.21 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | M24 (n=226, 232) | -8.91 mg/dL | Standard Deviation 65.24 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext FU M3 (n=115, 118) | 1.88 mg/dL | Standard Deviation 64.94 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | FU M3 (n=5, 4) | -4.08 mg/dL | Standard Deviation 32.08 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M18 (n=136, 138) | -10.32 mg/dL | Standard Deviation 63.11 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | FU M6 (n=161, 156) | -1.56 mg/dL | Standard Deviation 71.72 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M30 (n=127, 130) | -6.40 mg/dL | Standard Deviation 61.47 |
| Subcutaneous Insulin | Change From Baseline in Fasting Plasma Glucose (FPG) | Ext M1 (n=165, 162) | -7.34 mg/dL | Standard Deviation 60.98 |
Comparison: M390% CI: [-19.07, -5.71]
Comparison: M690% CI: [-22.11, -6.312]
Comparison: M1290% CI: [-19.07, -2.852]
Comparison: M2490% CI: [-20.89, -4.232]
Comparison: FU M390% CI: [-80.69, 47.019]
Comparison: FU M690% CI: [-9.257, 14.412]
Comparison: Ext M190% CI: [-19.37, 0.45]
Comparison: Ext M390% CI: [-20.11, 1.153]
Comparison: Ext M690% CI: [-21.95, 0.438]
Comparison: Ext M990% CI: [-16.98, 3.328]
Comparison: Ext M1290% CI: [-19.15, 4.579]
Comparison: Ext M1590% CI: [-13.76, 10.066]
Comparison: Ext M1890% CI: [-20.83, 2.79]
Comparison: Ext M2190% CI: [-18.99, 4.834]
Comparison: Ext M2490% CI: [-24.63, -0.429]
Comparison: Ext M2790% CI: [-30.45, -7.685]
Comparison: Ext M3090% CI: [-15.15, 8.705]
Comparison: Ext M3390% CI: [-21.09, 4.107]
Comparison: Ext M3690% CI: [-36.66, -7.105]
Comparison: Ext FU M390% CI: [-19.16, 9.812]
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Change from baseline: mean of (value of observed HbA1c \[%\] at treatment 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 (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline (n=315, 303) | 7.66 percent | Standard Deviation 1.12 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M30 (n=129, 129) | -0.20 percent | Standard Deviation 1.19 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M33(n=104, 116) | 8.54 percent | Standard Deviation 88.44 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M36 (n=55, 64) | -0.20 percent | Standard Deviation 1.15 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext FU M3 (n=117, 116) | -0.11 percent | Standard Deviation 1.4 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 6 (W6) (n=291, 280) | -0.64 percent | Standard Deviation 0.67 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M3 (n=296, 291) | -0.80 percent | Standard Deviation 0.86 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M6 (n=284, 287) | -0.67 percent | Standard Deviation 0.94 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M9 (n=270, 280) | -0.56 percent | Standard Deviation 0.98 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M12 (n=261, 263) | -0.45 percent | Standard Deviation 0.94 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M15(n=252, 258) | -0.43 percent | Standard Deviation 1 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M18(n=244, 241) | -0.42 percent | Standard Deviation 1.02 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M21 (n=236, 238) | -0.43 percent | Standard Deviation 1.04 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M24 (n=226, 234) | -0.35 percent | Standard Deviation 1.09 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | FU M3 (n=225, 226) | -0.41 percent | Standard Deviation 1.04 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | FU M6 (n=230, 230) | -0.27 percent | Standard Deviation 1.12 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M1 (n=167, 162) | -0.41 percent | Standard Deviation 1.16 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M3 (n=164, 162) | -0.33 percent | Standard Deviation 1.19 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M6 (n=157, 163) | -0.26 percent | Standard Deviation 1.11 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M9 (n=152, 157) | -0.11 percent | Standard Deviation 1.15 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M12 (n=150, 157) | -0.08 percent | Standard Deviation 1.19 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M15(n=146, 151) | -0.17 percent | Standard Deviation 1.3 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M18 (n=145, 145) | -0.20 percent | Standard Deviation 1.19 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M21(n=137, 147) | -0.13 percent | Standard Deviation 1.16 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M24 (n=131, 137) | -0.18 percent | Standard Deviation 1.21 |
| Inhaled Insulin (Exubera®) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M27(n=129, 132) | -0.18 percent | Standard Deviation 1.13 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M9 (n=152, 157) | -0.26 percent | Standard Deviation 1.13 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M24 (n=226, 234) | -0.48 percent | Standard Deviation 1.13 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M30 (n=129, 129) | -0.30 percent | Standard Deviation 1.19 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M24 (n=131, 137) | -0.23 percent | Standard Deviation 1.11 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M33(n=104, 116) | -0.18 percent | Standard Deviation 1.17 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | FU M3 (n=225, 226) | -0.44 percent | Standard Deviation 1.06 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M36 (n=55, 64) | -0.30 percent | Standard Deviation 1.18 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M12 (n=150, 157) | -0.17 percent | Standard Deviation 1.16 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext FU M3 (n=117, 116) | -0.17 percent | Standard Deviation 1.28 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline (n=315, 303) | 7.77 percent | Standard Deviation 1.12 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | FU M6 (n=230, 230) | -0.31 percent | Standard Deviation 1.06 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Week 6 (W6) (n=291, 280) | -0.60 percent | Standard Deviation 0.7 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M21(n=137, 147) | -0.20 percent | Standard Deviation 1.2 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M3 (n=296, 291) | -0.73 percent | Standard Deviation 0.89 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M1 (n=167, 162) | -0.40 percent | Standard Deviation 1.05 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M6 (n=284, 287) | -0.68 percent | Standard Deviation 1 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M15(n=146, 151) | -0.25 percent | Standard Deviation 1.15 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M9 (n=270, 280) | -0.61 percent | Standard Deviation 0.93 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M3 (n=164, 162) | -0.42 percent | Standard Deviation 1.05 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M12 (n=261, 263) | -0.58 percent | Standard Deviation 1 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M27(n=129, 132) | -0.28 percent | Standard Deviation 1.2 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M15(n=252, 258) | -0.51 percent | Standard Deviation 1 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M6 (n=157, 163) | -0.40 percent | Standard Deviation 1.1 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M18(n=244, 241) | -0.53 percent | Standard Deviation 1.06 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Ext M18 (n=145, 145) | -0.29 percent | Standard Deviation 1.17 |
| Subcutaneous Insulin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | M21 (n=236, 238) | -0.52 percent | Standard Deviation 1.02 |
Comparison: M390% CI: [-0.215, -0.023]
Comparison: M690% CI: [-0.133, 0.087]
Comparison: M990% CI: [-0.104, 0.124]
Comparison: M1290% CI: [-0.033, 0.214]
Comparison: M1590% CI: [-0.081, 0.185]
Comparison: M1890% CI: [-0.054, 0.234]
Comparison: M2190% CI: [-0.073, 0.208]
Comparison: M2490% CI: [-0.058, 0.257]
Comparison: FU M390% CI: [-0.143, 0.154]
Comparison: FU M690% CI: [-0.119, 0.19]
Comparison: Ext M190% CI: [-0.2, 0.161]
Comparison: Ext M390% CI: [-0.101, 0.263]
Comparison: Ext M690% CI: [-0.038, 0.32]
Comparison: Ext M990% CI: [-0.041, 0.342]
Comparison: Ext M1290% CI: [-0.09, 0.298]
Comparison: Ext M1590% CI: [-0.132, 0.279]
Comparison: Ext M1890% CI: [-0.111, 0.284]
Comparison: Ext M2190% CI: [-0.141, 0.27]
Comparison: Ext M2490% CI: [-0.156, 0.249]
Comparison: Ext M2790% CI: [-0.138, 0.272]
Comparison: Ext M3090% CI: [-0.171, 0.264]
Comparison: Ext M3390% CI: [-3.92, 23.569]
Comparison: Ext M3690% CI: [-0.316, 0.337]
Comparison: Ext FU M390% CI: [-0.245, 0.292]
Secondary
Cough Questionnaire
Clinician administered 6 question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (SC or inhaled), and productivity of cough; range 0 (indicates no symptoms) to 4 (indicates severe symptoms). Questionnaire administered at Week 0 then if and only if, cough is 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 study a limited set of analyses were undertaken and results of 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 3 or end of study
Population: FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of FVC were not summarized as planned.
Secondary
High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits
Number of subjects with Yes or No responses (within normal limits at specified time points = Yes or not within normal limits at specified time points = No) at observation when HRCT of thorax was not within normal limits at baseline. No response at observation further categorized as no significant change (NSC), more abnormal (\> Abn), or less abnormal (\< Abn).
Time frame: Baseline, M12, M24, Ext M6, Ext M18, Ext M36
Population: All subjects analysis substudy population: subjects from participating sites with a baseline and subsequent post-baseline HRCT measurement. Subjects were recruited prior to randomization; substudy enrollment continued until at least 50 subjects randomized to inhaled insulin were enrolled or until enrollment in the study was complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No (< Abn) | 1 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = Yes | 5 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No | 9 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No (NSC) | 8 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No (> Abn) | 1 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No (< Abn) | 0 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = Yes | 6 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No | 20 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No (NSC) | 19 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No (> Abn) | 0 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No (< Abn) | 1 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = Yes | 4 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No | 17 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No (NSC) | 17 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No (> Abn) | 0 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No (< Abn) | 0 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = Yes | 3 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No | 16 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No (NSC) | 15 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No (> Abn) | 1 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No (< Abn) | 0 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = Yes | 3 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No | 14 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No (NSC) | 12 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No (> Abn) | 1 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No (> Abn) | 1 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No (NSC) | 8 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = Yes | 2 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No (> Abn) | 0 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No | 8 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No (> Abn) | 1 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No (NSC) | 8 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No (< Abn) | 0 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No (> Abn) | 0 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No (< Abn) | 0 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M24 = No (< Abn) | 0 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No (NSC) | 7 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = Yes | 5 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = Yes | 3 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No | 16 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = Yes | 2 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No (NSC) | 11 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No | 9 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No (> Abn) | 2 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No (< Abn) | 0 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M12 = No (< Abn) | 3 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M6 = No (NSC) | 8 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = Yes | 6 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | Ext M18 = No | 7 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits | M24 = No | 9 participants |
Secondary
High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits
Number of subjects with Yes or No responses (within normal limits at specified time points = Yes or not within normal limits at specified time points = No) at observation when HRCT of thorax was within normal limits at baseline.
Time frame: Baseline, M12, M24, Ext M6, Ext M18, Ext M36
Population: All subjects analysis substudy population: subjects from participating sites with a baseline and subsequent post-baseline HRCT measurement. Subjects were recruited prior to randomization; substudy enrollment continued until at least 50 subjects randomized to inhaled insulin were enrolled or until enrollment in the study was complete.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M12 = Yes | 67 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M12 = No | 4 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M24 = Yes | 38 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M24 = No | 8 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M6 = Yes | 32 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M6 = No | 8 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M18 = Yes | 28 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M18 = No | 8 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M36 = Yes | 22 participants |
| Inhaled Insulin (Exubera®) | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M36 = No | 6 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M18 = No | 6 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M12 = Yes | 64 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M6 = No | 8 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M12 = No | 12 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M36 = No | 4 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M24 = Yes | 51 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M18 = Yes | 33 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | M24 = No | 10 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M36 = Yes | 27 participants |
| Subcutaneous Insulin | High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits | Ext M6 = Yes | 37 participants |
Secondary
Hypoglycemic Event Rates
Hypoglycemic event rate; hypoglycemic event identified by characteristic symptoms of hypoglycemia with no blood glucose (BG) check with prompt resolution with food intake, SC glucagon, or intravenous (IV) glucose; characteristic symptoms with BG of 59 mg/dL (3.2 mmol/L) or less with or without symptoms. Crude event rate = total events divided by subject months (elapsed number of months a subject was in the study at each time interval).
Time frame: Month 1 through extension Month 36
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 (Exubera®) | Hypoglycemic Event Rates | Ext M8 (n=158, 164) | 0.82 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M17 (n=252, 257) | 0.53 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M9 (n=158, 164) | 0.56 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M2 (n=307, 302) | 1.40 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M10 (n=156, 164) | 0.99 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M18 (n=246, 253) | 0.61 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M11 (n=153, 164) | 0.70 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M10 (n=273, 285) | 0.72 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M12 (n=152, 162) | 1.26 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M19 (n=245, 252) | 0.59 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M13 (n=152, 160) | 1.07 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M6 (n=283, 290) | 0.98 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M14 (n=151, 159) | 0.95 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M20 (n=242, 249) | 0.62 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M15 (n=149, 156) | 0.86 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M11 (n=267, 274) | 0.68 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M16 (n=149, 156) | 0.99 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M21 (n=241, 246) | 0.57 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M17 (n=148, 154) | 1.20 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M4 (n=289, 295) | 1.10 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M18 (n=146, 154) | 1.08 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M22 (n=236, 244) | 0.44 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M19 (n=143, 152) | 1.25 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M12 (n=264, 274) | 0.72 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M20 (n=142, 152) | 1.20 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M23 (n=236, 241) | 0.41 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M21 (n=141, 151) | 0.78 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M7 (n=280, 289) | 0.80 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M22 (n=141, 149) | 0.79 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M24 (n=229, 232) | 0.45 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M23 (n=139, 149) | 0.82 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M13 (n=263, 269) | 0.71 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M24 (n=138, 147) | 0.88 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M1 (n=172, 169) | 1.16 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M25 (n=137, 146) | 0.73 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M3 (n=297, 298) | 1.22 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M26 (n=137, 145) | 0.68 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M2 (n=171, 169) | 1.10 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M27 (n=137, 141) | 0.62 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M14 (n=260, 265) | 0.62 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M28 (n=135, 137) | 0.68 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M3 (n=169, 169) | 1.02 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M29 (n=135, 137) | 0.81 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M8 (n=276, 288) | 0.82 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M30 (n=133, 137) | 0.64 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M4 (n=167, 169) | 0.87 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M31 (n=124, 133) | 0.67 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M15 (n=256, 265) | 0.64 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M32 (n=117, 125) | 0.82 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M5 (n=165, 168) | 0.91 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M33 (n=100, 117) | 0.55 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M5 (n=284, 293) | 0.95 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M34 (n=84, 90) | 0.64 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M6 (n=162, 167) | 0.87 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M35 (n=66, 78) | 0.63 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M16 (n=254, 261) | 0.68 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M36 (n=51, 60) | 0.72 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Ext M7 (n=161, 167) | 1.10 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Overall comparative (n=315, 303) | 0.95 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M9 (n=275, 287) | 0.71 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | Overall extension (n=172, 169) | 0.89 event rate (events/subject months) |
| Inhaled Insulin (Exubera®) | Hypoglycemic Event Rates | M1 (n=315, 303) | 1.63 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Overall extension (n=172, 169) | 1.10 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M1 (n=315, 303) | 1.80 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M2 (n=307, 302) | 1.60 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M3 (n=297, 298) | 1.65 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M4 (n=289, 295) | 1.64 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M5 (n=284, 293) | 1.28 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M6 (n=283, 290) | 1.09 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M7 (n=280, 289) | 1.12 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M8 (n=276, 288) | 0.94 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M9 (n=275, 287) | 0.86 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M10 (n=273, 285) | 0.93 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M11 (n=267, 274) | 0.79 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M12 (n=264, 274) | 0.94 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M13 (n=263, 269) | 0.82 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M14 (n=260, 265) | 0.87 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M15 (n=256, 265) | 0.78 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M16 (n=254, 261) | 0.97 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M17 (n=252, 257) | 0.82 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M18 (n=246, 253) | 0.95 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M19 (n=245, 252) | 0.78 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M20 (n=242, 249) | 0.73 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M21 (n=241, 246) | 0.65 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M22 (n=236, 244) | 0.72 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M23 (n=236, 241) | 0.82 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | M24 (n=229, 232) | 0.66 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M1 (n=172, 169) | 1.16 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M2 (n=171, 169) | 1.33 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M3 (n=169, 169) | 1.12 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M4 (n=167, 169) | 1.44 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M5 (n=165, 168) | 1.18 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M6 (n=162, 167) | 1.20 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M7 (n=161, 167) | 1.41 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M8 (n=158, 164) | 1.34 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M9 (n=158, 164) | 1.25 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M10 (n=156, 164) | 1.11 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M11 (n=153, 164) | 0.92 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M12 (n=152, 162) | 1.25 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M13 (n=152, 160) | 1.14 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M14 (n=151, 159) | 1.01 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M15 (n=149, 156) | 1.25 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M16 (n=149, 156) | 1.23 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M17 (n=148, 154) | 1.01 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M18 (n=146, 154) | 1.05 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M19 (n=143, 152) | 1.21 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M20 (n=142, 152) | 1.08 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M21 (n=141, 151) | 1.15 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M22 (n=141, 149) | 1.08 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M23 (n=139, 149) | 1.06 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M24 (n=138, 147) | 1.11 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M25 (n=137, 146) | 1.22 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M26 (n=137, 145) | 1.25 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M27 (n=137, 141) | 1.04 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M28 (n=135, 137) | 0.87 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M29 (n=135, 137) | 0.91 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M30 (n=133, 137) | 0.87 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M31 (n=124, 133) | 1.32 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M32 (n=117, 125) | 0.81 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M33 (n=100, 117) | 0.89 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M34 (n=84, 90) | 0.57 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M35 (n=66, 78) | 0.80 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Ext M36 (n=51, 60) | 0.47 event rate (events/subject months) |
| Subcutaneous Insulin | Hypoglycemic Event Rates | Overall comparative (n=315, 303) | 1.19 event rate (events/subject months) |
Secondary
Insulin Antibodies
Observed values for insulin antibodies measured as micro units per milliliter (microU/mL).
Time frame: Baseline through extension Month 36
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 (Exubera®) | Insulin Antibodies | FU M6 (n=250, 227) | 6.55 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | W18 (n=275, 280) | 18.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M1 (n=165, 160) | 13.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M15 (n=252, 253) | 20.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M3 (n=159, 158) | 15.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Baseline (n=312, 300) | 1.05 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M6 (n=157, 156) | 12.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M18 (n=241, 239) | 20.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M9 (n=150, 157) | 11.50 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M6 (n=276, 279) | 20.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M12 (n=148, 154) | 13.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M21 (n=234, 233) | 19.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M15 (n=144, 147) | 10.50 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | W6 (n=289, 282) | 4.40 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M18 (n=140, 144) | 13.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M24 (n=226, 233) | 20.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M21 (n=136, 145) | 12.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M9 (n=267, 277) | 22.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M24 (n=130, 135) | 10.50 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | FU M1 (n=247, 226) | 14.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M27 (n=129, 131) | 12.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | W3 (n=270, 264) | 1.05 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M30 (n=125, 127) | 8.40 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | FU M3 (n=249, 229) | 8.50 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M33 (n=103, 114) | 9.20 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M12 (n=263, 263) | 19.00 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | Ext M36 (n=56, 63) | 5.75 microU/mL |
| Inhaled Insulin (Exubera®) | Insulin Antibodies | M3 (n=293, 289) | 12.00 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M36 (n=56, 63) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M3 (n=293, 289) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Baseline (n=312, 300) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | W3 (n=270, 264) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | W6 (n=289, 282) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | W18 (n=275, 280) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M6 (n=276, 279) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M9 (n=267, 277) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M12 (n=263, 263) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M15 (n=252, 253) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M18 (n=241, 239) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M21 (n=234, 233) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | M24 (n=226, 233) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | FU M1 (n=247, 226) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | FU M3 (n=249, 229) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | FU M6 (n=250, 227) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M1 (n=165, 160) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M3 (n=159, 158) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M6 (n=157, 156) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M9 (n=150, 157) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M12 (n=148, 154) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M15 (n=144, 147) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M18 (n=140, 144) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M21 (n=136, 145) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M24 (n=130, 135) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M27 (n=129, 131) | 2.50 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M30 (n=125, 127) | 1.05 microU/mL |
| Subcutaneous Insulin | Insulin Antibodies | Ext M33 (n=103, 114) | 1.05 microU/mL |
Secondary
Lipid Panel: Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, and Triglycerides
Lipid values for total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides measured as milligrams per deciliter (mg/dL).
Time frame: Week -4 through Month 24
Population: FAS: received at least 1 dose of study treatment. Due to early termination of study a limited set of analyses were undertaken and results of Lipids were not summarized as planned.
Secondary
Severe Hypoglycemic Event Rates
Severe hypoglycemic event rate; all 3 criteria were met: subject unable to treat self, exhibited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty awakening, suspected seizure, loss of consciousness); BG measurement ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, SC glucagon, or IV glucose. Crude event rate: total events divided by subject months multiplied by 100 (\[total events/subject months\]\*100). Subjects months: elapsed number of months subject was in study in each time interval.
Time frame: Month 1 through extension Month 36
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 (Exubera®) | Severe Hypoglycemic Event Rates | Ext M8 (n=158, 164) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M17 (n=252, 257) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M9 (n=158, 164) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M9 (n=275, 287) | 0.74 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M10 (n=156, 164) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M18 (n=246, 253) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M11 (n=153, 164) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M5 (n=284, 293) | 0.36 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M12 (n=152, 162) | 0.98 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M19 (n=245, 252) | 0.41 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M13 (n=152, 160) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M3 (n=297, 298) | 0.69 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M14 (n=151, 159) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M20 (n=242, 249) | 0.42 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M15 (n=149, 156) | 1.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M11 (n=267, 274) | 0.38 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M16 (n=149, 156) | 1.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M21 (n=241, 246) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M17 (n=148, 154) | 1.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M6 (n=283, 290) | 0.72 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M18 (n=146, 154) | 1.01 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M22 (n=236, 244) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M19 (n=143, 152) | 1.03 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M12 (n=264, 274) | 0.76 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M20 (n=142, 152) | 4.16 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M23 (n=236, 241) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M21 (n=141, 151) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M2 (n=307, 302) | 0.34 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M22 (n=141, 149) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M24 (n=229, 232) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M23 (n=139, 149) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M13 (n=263, 269) | 0.77 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M24 (n=138, 147) | 1.06 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M1 (n=172, 169 | 0.95 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M25 (n=137, 146) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M7 (n=280, 289) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M26 (n=137, 145) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M2 (n=171, 169) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M27 (n=137, 141) | 1.07 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M14 (n=260, 265) | 0.78 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M28 (n=135, 137) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M3 (n=169, 169) | 1.92 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M29 (n=135, 137) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M4 (n=289, 295) | 0.35 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M30 (n=133, 137) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M4 (n=167, 169) | 1.92 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M31 (n=124, 133) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M15 (n=256, 265) | 0.79 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M32 (n=117, 125) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M5 (n=165, 168) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M33 (n=100, 117) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M8 (n=276, 288) | 0.37 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M34 (n=84, 90) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M6 (n=162, 167) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M35 (n=66, 78) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M16 (n=254, 261) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M36 (n=51, 60) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Ext M7 (n=161, 167) | 0.00 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Overall comparative (n=315, 303) | 0.45 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M1 (n=315, 303) | 0.98 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | Overall extension (n=172, 169) | 0.50 event rate (events/subject months*100) |
| Inhaled Insulin (Exubera®) | Severe Hypoglycemic Event Rates | M10 (n=273, 285) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Overall extension (n=172, 169) | 1.17 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M1 (n=315, 303) | 0.67 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M2 (n=307, 302) | 0.34 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M3 (n=297, 298) | 0.34 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M4 (n=289, 295) | 1.38 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M5 (n=284, 293) | 1.74 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M6 (n=283, 290) | 2.10 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M7 (n=280, 289) | 0.70 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M8 (n=276, 288) | 0.70 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M9 (n=275, 287) | 0.35 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M10 (n=273, 285) | 0.36 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M11 (n=267, 274) | 0.37 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M12 (n=264, 274) | 0.37 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M13 (n=263, 269) | 0.76 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M14 (n=260, 265) | 0.38 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M15 (n=256, 265) | 0.77 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M16 (n=254, 261) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M17 (n=252, 257) | 0.40 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M18 (n=246, 253) | 0.40 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M19 (n=245, 252) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M20 (n=242, 249) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M21 (n=241, 246) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M22 (n=236, 244) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M23 (n=236, 241) | 0.85 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | M24 (n=229, 232) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M1 (n=172, 169 | 0.93 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M2 (n=171, 169) | 1.87 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M3 (n=169, 169) | 0.94 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M4 (n=167, 169) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M5 (n=165, 168) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M6 (n=162, 167) | 0.94 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M7 (n=161, 167) | 1.90 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M8 (n=158, 164) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M9 (n=158, 164) | 2.86 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M10 (n=156, 164) | 3.81 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M11 (n=153, 164) | 3.86 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M12 (n=152, 162) | 3.91 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M13 (n=152, 160) | 0.98 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M14 (n=151, 159) | 1.96 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M15 (n=149, 156) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M16 (n=149, 156) | 1.96 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M17 (n=148, 154) | 0.99 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M18 (n=146, 154) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M19 (n=143, 152) | 0.99 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M20 (n=142, 152) | 0.99 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M21 (n=141, 151) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M22 (n=141, 149) | 1.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M23 (n=139, 149) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M24 (n=138, 147) | 2.02 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M25 (n=137, 146) | 1.01 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M26 (n=137, 145) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M27 (n=137, 141) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M28 (n=135, 137) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M29 (n=135, 137) | 1.06 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M30 (n=133, 137) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M31 (n=124, 133) | 1.15 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M32 (n=117, 125) | 3.58 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M33 (n=100, 117) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M34 (n=84, 90) | 1.89 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M35 (n=66, 78) | 0.00 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Ext M36 (n=51, 60) | 0.82 event rate (events/subject months*100) |
| Subcutaneous Insulin | Severe Hypoglycemic Event Rates | Overall comparative (n=315, 303) | 0.65 event rate (events/subject months*100) |
Secondary
Total Daily Long-acting Insulin (Adjusted for Body Weight)
Total daily dose of long-acting insulin adjusted for body weight (units per kilogram \[kg\]). Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine.
Time frame: Month 3 through extension Month 36
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 (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M3 (n=301, 298) | 0.51 units/kg | Standard Deviation 0.29 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M6 (n=289, 291) | 0.50 units/kg | Standard Deviation 0.29 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M9 (n=275, 284) | 0.50 units/kg | Standard Deviation 0.29 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M12 (n=266, 270) | 0.51 units/kg | Standard Deviation 0.3 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M15 (n=258, 260) | 0.52 units/kg | Standard Deviation 0.31 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M18 (n=243, 242) | 0.53 units/kg | Standard Deviation 0.31 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M21 (n=240, 240) | 0.53 units/kg | Standard Deviation 0.32 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M24 (n=229, 237) | 0.54 units/kg | Standard Deviation 0.32 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M1 (n=167, 164) | 0.53 units/kg | Standard Deviation 0.33 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M3 (n=165, 162) | 0.53 units/kg | Standard Deviation 0.34 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M6 (n=159, 164) | 0.54 units/kg | Standard Deviation 0.34 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M9 (n=156, 158) | 0.54 units/kg | Standard Deviation 0.35 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M12 (n=151, 158) | 0.54 units/kg | Standard Deviation 0.36 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M15 (n=148, 149) | 0.54 units/kg | Standard Deviation 0.36 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M18 (n=145, 145) | 0.54 units/kg | Standard Deviation 0.37 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M21 (n=137, 148) | 0.54 units/kg | Standard Deviation 0.37 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M24 (n=131, 137) | 0.55 units/kg | Standard Deviation 0.39 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M27 (n=132, 133) | 0.56 units/kg | Standard Deviation 0.39 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M30 (n=131, 130) | 0.56 units/kg | Standard Deviation 0.41 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M33 (n=104, 116) | 0.56 units/kg | Standard Deviation 0.37 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M36 (n=56, 65) | 0.53 units/kg | Standard Deviation 0.37 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M6 (n=159, 164) | 0.60 units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M3 (n=301, 298) | 0.54 units/kg | Standard Deviation 0.27 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M30 (n=131, 130) | 0.62 units/kg | Standard Deviation 0.33 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M6 (n=289, 291) | 0.54 units/kg | Standard Deviation 0.28 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M9 (n=156, 158) | 0.60 units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M9 (n=275, 284) | 0.55 units/kg | Standard Deviation 0.29 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M24 (n=131, 137) | 0.61 units/kg | Standard Deviation 0.34 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M12 (n=266, 270) | 0.55 units/kg | Standard Deviation 0.29 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M12 (n=151, 158) | 0.60 units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M15 (n=258, 260) | 0.56 units/kg | Standard Deviation 0.3 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M36 (n=56, 65) | 0.61 units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M18 (n=243, 242) | 0.57 units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M15 (n=148, 149) | 0.61 units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M21 (n=240, 240) | 0.57 units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M27 (n=132, 133) | 0.61 units/kg | Standard Deviation 0.33 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | M24 (n=229, 237) | 0.58 units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M18 (n=145, 145) | 0.61 units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M1 (n=167, 164) | 0.59 units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M33 (n=104, 116) | 0.61 units/kg | Standard Deviation 0.34 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M3 (n=165, 162) | 0.59 units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin (Adjusted for Body Weight) | Ext M21 (n=137, 148) | 0.61 units/kg | Standard Deviation 0.32 |
Secondary
Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight)
Total daily long-acting insulin dose unadjusted for body weight. Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine.
Time frame: Month 3 through extension Month 36
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 (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M3 (n=301, 298) | 44.10 units | Standard Deviation 25.6 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M6 (n=289, 291) | 44.03 units | Standard Deviation 26.27 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M9 (n=275, 284) | 43.64 units | Standard Deviation 26.17 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M12 (n=266, 270) | 44.62 units | Standard Deviation 27.43 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M15 (n=258, 260) | 45.02 units | Standard Deviation 27.76 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M18 (n=243, 242) | 46.07 units | Standard Deviation 27.77 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M21 (n=240, 240) | 46.67 units | Standard Deviation 29.06 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M24 (n=229, 237) | 46.62 units | Standard Deviation 28.55 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M1 (n=167, 164) | 45.29 units | Standard Deviation 28 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M3 (n=165, 162) | 45.76 units | Standard Deviation 28.61 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M6 (n=159, 164) | 45.89 units | Standard Deviation 28.61 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M9 (n=156, 158) | 46.51 units | Standard Deviation 29.34 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M12 (n=151, 158) | 46.52 units | Standard Deviation 29.84 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M15 (n=148, 149) | 46.39 units | Standard Deviation 30.12 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M18 (n=145, 145) | 46.31 units | Standard Deviation 31.17 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M21 (n=137, 148) | 46.49 units | Standard Deviation 31.17 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M24 (n=131, 137) | 47.21 units | Standard Deviation 32.42 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M27 (n=132, 133) | 48.13 units | Standard Deviation 32.76 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M30 (n=131, 130) | 48.13 units | Standard Deviation 33.41 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M33 (n=104, 116) | 48.38 units | Standard Deviation 32.47 |
| Inhaled Insulin (Exubera®) | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M36 (n=56, 65) | 46.42 units | Standard Deviation 31.91 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M6 (n=159, 164) | 52.18 units | Standard Deviation 28.85 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M3 (n=301, 298) | 47.98 units | Standard Deviation 25.06 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M30 (n=131, 130) | 53.22 units | Standard Deviation 29.85 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M6 (n=289, 291) | 47.31 units | Standard Deviation 25.47 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M9 (n=156, 158) | 52.32 units | Standard Deviation 28.89 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M9 (n=275, 284) | 48.11 units | Standard Deviation 26.02 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M24 (n=131, 137) | 52.18 units | Standard Deviation 30.33 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M12 (n=266, 270) | 48.01 units | Standard Deviation 26.02 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M12 (n=151, 158) | 51.72 units | Standard Deviation 29.06 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M15 (n=258, 260) | 48.37 units | Standard Deviation 26.48 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M36 (n=56, 65) | 53.47 units | Standard Deviation 28.96 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M18 (n=243, 242) | 48.93 units | Standard Deviation 27.6 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M15 (n=148, 149) | 52.92 units | Standard Deviation 29.83 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M21 (n=240, 240) | 49.84 units | Standard Deviation 28.73 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M27 (n=132, 133) | 52.42 units | Standard Deviation 29.87 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | M24 (n=229, 237) | 50.34 units | Standard Deviation 29.31 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M18 (n=145, 145) | 52.37 units | Standard Deviation 29.78 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M1 (n=167, 164) | 51.29 units | Standard Deviation 28.45 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M33 (n=104, 116) | 51.93 units | Standard Deviation 30.65 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M3 (n=165, 162) | 51.62 units | Standard Deviation 28.71 |
| Subcutaneous Insulin | Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight) | Ext M21 (n=137, 148) | 52.68 units | Standard Deviation 29.4 |
Secondary
Total Daily Short-acting Insulin Dose (Adjusted for Body Weight)
Total daily dose of short-acting insulin adjusted for body weight. Short-acting insulin (mg) for the inhaled insulin treatment group was inhaled insulin (mg divided by kg); short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin (units divided by kg).
Time frame: Month 3 through extension Month 36
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 (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M9 (n=275, 285) | 0.16 mg/kg, units/kg | Standard Deviation 0.08 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M3 (n=302, 299) | 0.15 mg/kg, units/kg | Standard Deviation 0.07 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M6 (n=290, 292) | 0.15 mg/kg, units/kg | Standard Deviation 0.08 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M12 (n=266, 270) | 0.17 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M15 (n=258, 261) | 0.17 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M18 (n=245, 242) | 0.17 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M21 (n=240, 242) | 0.17 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M24 (n=229, 238) | 0.18 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M1 (n=167, 164) | 0.16 mg/kg, units/kg | Standard Deviation 0.09 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M3 (n=165, 163) | 0.17 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M6 (n=159, 165) | 0.17 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M9 (n=156, 161) | 0.17 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M12 (n=151, 160) | 0.18 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M15 (n=148, 151) | 0.18 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M18 (n=145, 146) | 0.18 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M21 (n=138, 149) | 0.18 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M24 (n=131, 138) | 0.18 mg/kg, units/kg | Standard Deviation 0.1 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M27 (n=132, 134) | 0.19 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M30 (n=131, 131) | 0.19 mg/kg, units/kg | Standard Deviation 0.12 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M33 (n=105, 117) | 0.19 mg/kg, units/kg | Standard Deviation 0.11 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M36 (n=56, 66) | 0.19 mg/kg, units/kg | Standard Deviation 0.12 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M6 (n=159, 165) | 0.41 mg/kg, units/kg | Standard Deviation 0.3 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M9 (n=275, 285) | 0.36 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M30 (n=131, 131) | 0.46 mg/kg, units/kg | Standard Deviation 0.34 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M3 (n=302, 299) | 0.36 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M9 (n=156, 161) | 0.42 mg/kg, units/kg | Standard Deviation 0.3 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M6 (n=290, 292) | 0.36 mg/kg, units/kg | Standard Deviation 0.22 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M24 (n=131, 138) | 0.45 mg/kg, units/kg | Standard Deviation 0.35 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M12 (n=266, 270) | 0.37 mg/kg, units/kg | Standard Deviation 0.23 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M12 (n=151, 160) | 0.43 mg/kg, units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M15 (n=258, 261) | 0.37 mg/kg, units/kg | Standard Deviation 0.24 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M36 (n=56, 66) | 0.48 mg/kg, units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M18 (n=245, 242) | 0.38 mg/kg, units/kg | Standard Deviation 0.25 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M15 (n=148, 151) | 0.42 mg/kg, units/kg | Standard Deviation 0.31 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M21 (n=240, 242) | 0.39 mg/kg, units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M27 (n=132, 134) | 0.45 mg/kg, units/kg | Standard Deviation 0.34 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | M24 (n=229, 238) | 0.40 mg/kg, units/kg | Standard Deviation 0.27 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M18 (n=145, 146) | 0.44 mg/kg, units/kg | Standard Deviation 0.32 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M1 (n=167, 164) | 0.40 mg/kg, units/kg | Standard Deviation 0.3 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M33 (n=105, 117) | 0.47 mg/kg, units/kg | Standard Deviation 0.36 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M3 (n=165, 163) | 0.41 mg/kg, units/kg | Standard Deviation 0.26 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Adjusted for Body Weight) | Ext M21 (n=138, 149) | 0.43 mg/kg, units/kg | Standard Deviation 0.33 |
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 (milligrams \[mg\]) for the inhaled insulin treatment group was inhaled insulin; short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin.
Time frame: Month 3 through extension Month 36
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 (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M3 (n=302, 299) | 12.66 mg, units | Standard Deviation 6.8 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M6 (n=290, 292) | 13.18 mg, units | Standard Deviation 6.9 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M9 (n=275, 285) | 13.57 mg, units | Standard Deviation 7.57 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M12 (n=266, 270) | 14.40 mg, units | Standard Deviation 7.9 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M15 (n=258, 261) | 14.70 mg, units | Standard Deviation 8.06 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M18 (n=245, 242) | 14.91 mg, units | Standard Deviation 8.41 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M21 (n=240, 242) | 15.09 mg, units | Standard Deviation 8.55 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M24 (n=229, 238) | 15.43 mg, units | Standard Deviation 8.65 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M1 (n=167, 164) | 13.89 mg, units | Standard Deviation 8.47 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M3 (n=165, 163) | 14.62 mg, units | Standard Deviation 9.18 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M6 (n=159, 165) | 14.62 mg, units | Standard Deviation 9.16 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M9 (n=156, 161) | 14.82 mg, units | Standard Deviation 9.1 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M12 (n=151, 160) | 15.42 mg, units | Standard Deviation 9.81 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M15 (n=148, 151) | 15.48 mg, units | Standard Deviation 9.9 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M18 (n=145, 146) | 15.57 mg, units | Standard Deviation 9.93 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M21 (n=138, 149) | 15.94 mg, units | Standard Deviation 10.41 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M24 (n=131, 138) | 15.46 mg, units | Standard Deviation 9.7 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M27 (n=132, 134) | 16.25 mg, units | Standard Deviation 10.3 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M30 (n=131, 131) | 16.56 mg, units | Standard Deviation 10.63 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M33 (n=105, 117) | 16.51 mg, units | Standard Deviation 10.43 |
| Inhaled Insulin (Exubera®) | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M36 (n=56, 66) | 17.25 mg, units | Standard Deviation 11.3 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M6 (n=159, 165) | 35.43 mg, units | Standard Deviation 24.8 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M3 (n=302, 299) | 31.15 mg, units | Standard Deviation 18.75 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M30 (n=131, 131) | 39.01 mg, units | Standard Deviation 28.66 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M6 (n=290, 292) | 31.73 mg, units | Standard Deviation 19.08 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M9 (n=156, 161) | 35.68 mg, units | Standard Deviation 24.72 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M9 (n=275, 285) | 31.58 mg, units | Standard Deviation 18.89 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M24 (n=131, 138) | 38.51 mg, units | Standard Deviation 29.06 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M12 (n=266, 270) | 31.94 mg, units | Standard Deviation 19.29 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M12 (n=151, 160) | 36.56 mg, units | Standard Deviation 26.34 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M15 (n=258, 261) | 31.88 mg, units | Standard Deviation 19.37 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M36 (n=56, 66) | 42.34 mg, units | Standard Deviation 28.72 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M18 (n=245, 242) | 32.79 mg, units | Standard Deviation 20.7 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M15 (n=148, 151) | 36.27 mg, units | Standard Deviation 25.51 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M21 (n=240, 242) | 33.18 mg, units | Standard Deviation 20.92 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M27 (n=132, 134) | 38.54 mg, units | Standard Deviation 28.13 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | M24 (n=229, 238) | 34.04 mg, units | Standard Deviation 21.84 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M18 (n=145, 146) | 37.37 mg, units | Standard Deviation 26.29 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M1 (n=167, 164) | 34.52 mg, units | Standard Deviation 24.52 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M33 (n=105, 117) | 40.33 mg, units | Standard Deviation 30.81 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M3 (n=165, 163) | 35.29 mg, units | Standard Deviation 23.19 |
| Subcutaneous Insulin | Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight) | Ext M21 (n=138, 149) | 36.80 mg, units | Standard Deviation 27.09 |
Secondary
Total Lung Capacity (TLC)
Total Lung Capacity measured in liters (L).
Time frame: Baseline through extension follow up Month 3
Population: FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of TLC 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 3 or end of study
Population: FAS FEV1. Due to early termination of study a limited set of analyses were undertaken and results of TDI were not summarized as planned.