Diabetes Mellitus, Type 2
Conditions
Keywords
Insulin Glargine Diabetes HbA1c
Brief summary
This study is to determine if inhaled insulin is effective in treating type 2 diabetes mellitus.
Interventions
DRUGInsulin glargine
Insulin glargine, label instruction initiation dose (10 units), and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.
Initiation dose of one mg per meal, and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age \> 30 years and ≤ 75 years with a diagnosis of type 2 diabetes mellitus made \> 6 months prior to study entry * Screening HbA1c \> 7.0% * Currently treated on a stable dose of at least 2 oral antidiabetic agents for at least 3 months prior to study entry; including a sulfonylurea and/or metformin, and/or a thiazolidinedione
Exclusion criteria
Smoking within last 6 months PFTs outside of range * Type 1 diabetes mellitus * Type 2 diabetes mellitus currently (last three months) treated with an insulin regimen (alone or with Oral Antidiabetic Agents) * Active liver disease; significantly-impaired hepatic function, as shown by, but not limited to, alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate transaminase (AST) serum glutamic-oxaloacetic transaminase (SGOT) above 2x the upper limit of normal as measured at visit 1. However, patients with elevated ALT \>1.5 upper limit of normal as a result of hepatic steatosis are permitted to enter the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the Per Protocol (PP) Population | Baseline, Week 26 | HbA1c lab value: Change = value at Week 26 minus value at Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26 | Week 26 | Percentage of subjects with glycosylated hemoglobin A1c lab value less than 6.5%. |
| Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26 | Week 26 | Percentage of subjects with glycosylated hemoglobin A1c lab value less than 7.0%. |
| Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26 | Week 26 | Number of subjects with glycosylated hemoglobin A1c lab value less than 8.0%. |
| Change From Baseline in Fasting Plasma Glucose at Week 26 | Baseline, Week 26 | Fasting plasma glucose lab value: Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Baseline, Week 26 | Postprandial blood glucose lab value (Time 0 min \[fasting\], Time 30 min, Time 60 min, Time 90 min, Time 120 min, Time 180 min): Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Baseline, Week 26 | Post-prandial=after a meal. 8-point scale: (1 = before breakfast, 2 = 2 hours post breakfast, 3 = before lunch, 4 = 2 hours post lunch, 5 = before dinner, 6 = 2 hours post dinner, 7 = at bedtime, 8 = overnight \[between 2 and 4 am\]). Postprandial blood glucose lab value: Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in Lipids at Week 26 | Baseline, Week 26 | Lipid (total cholesterol, high density lipoprotein cholesterol \[HDL-c\], low density lipoprotein cholesterol \[LDL-c\], triglycerides) lab value: Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | Baseline, Week 26 | CV biomarker (hs-CRP, Leptin, and Spot Urine Microalbumin) lab value: Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 | Baseline, Week 26 | CV biomarker (adiponectin and ApoB) lab value: Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26 | Baseline, Week 26 | 24-Hour CGMS glucose lab value was obtained using the Medtronic MiniMed CGMS. Not all subjects were offered the opportunity to participate in this assessment. Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in Mean Standard Deviation (SD) of 24-Hour Glucose Values Measured by CGMS at Week 26 | Baseline, Week 26 | SD of 24-Hour CGMS glucose lab value obtained using the Medtronic MiniMed CGMS. Not all subjects were offered the opportunity to participate in this assessment. Change = value at Week 26 minus value at Baseline. |
| Number of Subjects With Hypoglycemic Events | Months 1 to 7 | A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. An event was severe if the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. |
| Number of Total Hypoglycemic Events | Months 1 to 7 | A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. Total=events during the study. |
| Number of Total Subject Months of Treatment | Months 1 to 7 | Number of total subject months of treatment. Subject months = number of days from start of treatment to the last day of active treatment + 1 day lag, including off-drug time)/30.44. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. |
| Crude Hypoglycemic Event Rate | Months 1 to 7 | crude event rate=(events)/(subject-months). Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. |
| Number of Nocturnal Hypoglycemic Events | Months 1 to 7 | A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Nocturnal hypoglycemia=event occuring from midnight to 5:59 am. |
| Change From Baseline in Body Weight at Week 26 | Baseline, Week 26 | Body weight value: Change = value at Week 26 minus value at Baseline. |
| Change From Baseline in Body Mass Index (BMI) at Week 26 | Baseline, Week 26 | BMI value (kg/m2): Change = value at Week 26 minus value at Baseline. |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Human Insulin Initiation dose of 1 milligram per meal, and individually adjusted doses, per subject's blood glucose, over the 6 month study, in addition to oral agents. | 212 |
| Insulin Glargine Insulin glargine, label instruction initiation dose (10 units), and individually adjusted doses, per subject's blood glucose, over the six months study, in addition to oral agents. | 190 |
| Total | 402 |
Baseline characteristics
| Characteristic | Inhaled Human Insulin | Insulin Glargine | Total |
|---|---|---|---|
| Age, Customized 18 to 44 years | 27 participants | 26 participants | 53 participants |
| Age, Customized 45 to 65 years | 151 participants | 125 participants | 276 participants |
| Age, Customized >=65 years | 34 participants | 39 participants | 73 participants |
| Gender Female | 92 Participants | 84 Participants | 176 Participants |
| Gender Male | 120 Participants | 106 Participants | 226 Participants |
| Sex: Female, Male Female | 92 Participants | 84 Participants | 176 Participants |
| Sex: Female, Male Male | 120 Participants | 106 Participants | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 177 / — | 142 / — |
| serious Total, serious adverse events | 9 / — | 4 / — |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the Per Protocol (PP) Population
HbA1c lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: Per protocol (PP)=Full Analysis Set (FAS) subjects (i.e., had \>=1 study drug dose and \>=1 post-baseline measurement) with \>=12 weeks treatment and no major protocol violation. LOCF imputed missing data with any post-baseline visit. Number of subjects with HbA1c values at Baseline and Week 26: inhaled human insulin n=154, insulin glargine n=157.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the Per Protocol (PP) Population | -2.01 percent | Standard Deviation 1.39 |
| Insulin Glargine | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the Per Protocol (PP) Population | -1.75 percent | Standard Deviation 1.4 |
Comparison: The null hypothesis was that the inhaled human insulin group was inferior to the insulin glargine group with respect to 26-week change from baseline in HbA1c, while the alternate hypothesis is that the inhaled human insulin group was not inferior to the insulin glargine group with respect to 26-week change from baseline in HbA1c, given the predetermined non-inferiority margin of 0.4%.p-value: <0.000195% CI: [-0.38, 0]ANCOVA
Comparison: With an established non-inferiority claim, an additional test for superiority was conducted (ie, the margin was 0.0%).p-value: 0.051695% CI: [-0.38, 0]ANCOVA
Secondary
Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26
24-Hour CGMS glucose lab value was obtained using the Medtronic MiniMed CGMS. Not all subjects were offered the opportunity to participate in this assessment. Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS-CGMS=all subjects with at least 1 study drug dose, at least 1 post-baseline measurement, and who participated in a 24-hour CGMS substudy. LOCF imputed missing data with any post-baseline visit. Number of subjects who participated in the substudy with 24-hour CGMS values at Baseline and Week 26: inhaled human insulin n=2, insulin glargine n=8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26 | -36.53 mg/dL | Standard Deviation 33.96 |
| Insulin Glargine | Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26 | -35.63 mg/dL | Standard Deviation 58.19 |
p-value: 0.185695% CI: [-43.37, 160.77]ANCOVA
Secondary
Change From Baseline in Body Mass Index (BMI) at Week 26
BMI value (kg/m2): Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with BMI measurements at Baseline and Week 26: inhaled human insulin n=192, insulin glargine n=183.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Body Mass Index (BMI) at Week 26 | 1.22 kg/m2 | Standard Deviation 1.66 |
| Insulin Glargine | Change From Baseline in Body Mass Index (BMI) at Week 26 | 0.80 kg/m2 | Standard Deviation 1.3 |
p-value: 0.005395% CI: [0.12, 0.71]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 26
Body weight value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with body weight measurements at Baseline and Week 26: inhaled human insulin n=192, insulin glargine n=183.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Body Weight at Week 26 | 3.55 kg | Standard Deviation 4.74 |
| Insulin Glargine | Change From Baseline in Body Weight at Week 26 | 2.33 kg | Standard Deviation 3.8 |
p-value: 0.005595% CI: [0.35, 2.04]ANCOVA
Secondary
Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26
CV biomarker (hs-CRP, Leptin, and Spot Urine Microalbumin) lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with CV biomarker data (hs-CRP, leptin, and spot urine microalbumin) at Baseline and Week 26: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | hs-CRP, Week 26 (n=198, 187) | 0.61 mg/L | Standard Deviation 4.56 |
| Inhaled Human Insulin | Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | Leptin, Week 26 (n=193, 186) | 3.68 mg/L | Standard Deviation 13.5 |
| Inhaled Human Insulin | Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | Spot Urine Microalbumin, Week 26 (n=183, 169) | 3.47 mg/L | Standard Deviation 96.48 |
| Insulin Glargine | Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | hs-CRP, Week 26 (n=198, 187) | 0.32 mg/L | Standard Deviation 3.69 |
| Insulin Glargine | Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | Leptin, Week 26 (n=193, 186) | 4.41 mg/L | Standard Deviation 10.5 |
| Insulin Glargine | Change From Baseline in Cardiovascular (CV) Biomarkers High Sensitivity C-reactive Protein (Hs-CRP), Leptin, and Spot Urine Microalbumin at Week 26 | Spot Urine Microalbumin, Week 26 (n=183, 169) | 3.70 mg/L | Standard Deviation 54.53 |
Comparison: hs-CRP at Week 26.p-value: 0.567395% CI: [-0.58, 1.06]ANCOVA
Comparison: Leptin at Week 26.p-value: 0.609995% CI: [-2.97, 1.75]ANCOVA
Comparison: Spot urine microalbumin at Week 26.p-value: 0.768495% CI: [-12.94, 17.51]ANCOVA
Secondary
Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26
CV biomarker (adiponectin and ApoB) lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with CV biomarker data (adiponectin and ApoB) at Baseline and Week 26: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 | Adiponectin, Week 26 (n=195, 184) | 0.23 mg/mL | Standard Deviation 5.58 |
| Inhaled Human Insulin | Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 | ApoB, Week 26 (n=198, 187) | -0.06 mg/mL | Standard Deviation 0.19 |
| Insulin Glargine | Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 | Adiponectin, Week 26 (n=195, 184) | -0.32 mg/mL | Standard Deviation 5.15 |
| Insulin Glargine | Change From Baseline in CV Biomarkers Adiponectin and Apolipoprotein B (ApoB) at Week 26 | ApoB, Week 26 (n=198, 187) | -0.06 mg/mL | Standard Deviation 0.17 |
Comparison: Adiponectin at Week 26.p-value: 0.500595% CI: [-0.69, 1.42]ANCOVA
Comparison: ApoB at Week 26.p-value: 0.68595% CI: [-0.03, 0.04]ANCOVA
Secondary
Change From Baseline in Diabetes Treatment Satisfaction Questionnaire-Status, Diabetes Treatment Satisfaction Questionnaire-Change, Diabetes-39, Mental Health Inventory-17, and SF-36 Vitality Domain Questionnaire
Due to cancellation of the EXUBERA program, the collected Patient Reported Outcome (PRO) data, including the Diabetes Treatment Satisfaction Questionnaire-Status, Diabetes Treatment Satisfaction Questionnaire-Change, Diabetes-39, Mental Health Inventory-17, and SF-36 vitality domain questionnaire were not summarized, and no statistical analyses were performed.
Time frame: Baseline, Week 26
Secondary
Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26
Postprandial blood glucose lab value (Time 0 min \[fasting\], Time 30 min, Time 60 min, Time 90 min, Time 120 min, Time 180 min): Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with fasting and postprandial blood glucose measurements determined by standardized meal tolerance tests at Baseline and Week 26: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 0 at Week 26 (n=105, 119) | -35.22 mg/dL | Standard Deviation 51.12 |
| Inhaled Human Insulin | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 30 at Week 26 (n=95, 107) | -49.91 mg/dL | Standard Deviation 62.41 |
| Inhaled Human Insulin | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 60 at Week 26 (n=110, 118) | -56.83 mg/dL | Standard Deviation 69.81 |
| Inhaled Human Insulin | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 90 at Week 26 (n=114, 120) | -64.94 mg/dL | Standard Deviation 75.67 |
| Inhaled Human Insulin | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 120 at Week 26 (n=113, 124) | -66.59 mg/dL | Standard Deviation 74.69 |
| Inhaled Human Insulin | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 180 at Week 26 (n=114, 122) | -66.99 mg/dL | Standard Deviation 74.19 |
| Insulin Glargine | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 120 at Week 26 (n=113, 124) | -54.89 mg/dL | Standard Deviation 63.02 |
| Insulin Glargine | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 0 at Week 26 (n=105, 119) | -61.16 mg/dL | Standard Deviation 54.68 |
| Insulin Glargine | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 90 at Week 26 (n=114, 120) | -58.85 mg/dL | Standard Deviation 64.58 |
| Insulin Glargine | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 30 at Week 26 (n=95, 107) | -66.02 mg/dL | Standard Deviation 62.32 |
| Insulin Glargine | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 180 at Week 26 (n=114, 122) | -51.27 mg/dL | Standard Deviation 59.92 |
| Insulin Glargine | Change From Baseline in Fasting and Postprandial Blood Glucose as Determined by Standardized Meal Tolerance Tests at Week 26 | Time 60 at Week 26 (n=110, 118) | -64.77 mg/dL | Standard Deviation 64.47 |
Comparison: Time 0 (fasting) at Week 26.p-value: <0.000195% CI: [22.66, 43.25]ANCOVA
Comparison: Time 30 at Week 26.p-value: <0.000195% CI: [16.55, 40.59]ANCOVA
Comparison: Time 60 at Week 26.p-value: 0.004495% CI: [5.96, 31.96]ANCOVA
Comparison: Time 90 at Week 26.p-value: 0.316895% CI: [-6.45, 19.83]ANCOVA
Comparison: Time 120 at Week 26.p-value: 0.922295% CI: [-12.12, 13.39]ANCOVA
Comparison: Time 180 at Week 26.p-value: 0.69595% CI: [-14.51, 9.69]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 26
Fasting plasma glucose lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with fasting plasma glucose at Baseline and Week 26: inhaled human insulin n=202, insulin glargine n=189.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Fasting Plasma Glucose at Week 26 | -52.77 mg/dL | Standard Deviation 69.48 |
| Insulin Glargine | Change From Baseline in Fasting Plasma Glucose at Week 26 | -53.50 mg/dL | Standard Deviation 62.92 |
p-value: 0.609195% CI: [-7.31, 12.46]ANCOVA
Secondary
Change From Baseline in Lipids at Week 26
Lipid (total cholesterol, high density lipoprotein cholesterol \[HDL-c\], low density lipoprotein cholesterol \[LDL-c\], triglycerides) lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with lipids data at Baseline and Week 26: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Lipids at Week 26 | Total cholesterol, Week 26 (n=197, 186) | -2.80 mg/dL | Standard Deviation 31.97 |
| Inhaled Human Insulin | Change From Baseline in Lipids at Week 26 | HDL-c, Week 26 (n=197, 186) | 2.97 mg/dL | Standard Deviation 6.99 |
| Inhaled Human Insulin | Change From Baseline in Lipids at Week 26 | LDL-c, Week 26 (n=197, 186) | -2.09 mg/dL | Standard Deviation 25.74 |
| Inhaled Human Insulin | Change From Baseline in Lipids at Week 26 | Triglycerides, Week 26 (n=197, 187) | -42.65 mg/dL | Standard Deviation 87.7 |
| Insulin Glargine | Change From Baseline in Lipids at Week 26 | Triglycerides, Week 26 (n=197, 187) | -46.23 mg/dL | Standard Deviation 147.8 |
| Insulin Glargine | Change From Baseline in Lipids at Week 26 | Total cholesterol, Week 26 (n=197, 186) | -6.19 mg/dL | Standard Deviation 29.95 |
| Insulin Glargine | Change From Baseline in Lipids at Week 26 | LDL-c, Week 26 (n=197, 186) | -3.71 mg/dL | Standard Deviation 23.63 |
| Insulin Glargine | Change From Baseline in Lipids at Week 26 | HDL-c, Week 26 (n=197, 186) | 0.69 mg/dL | Standard Deviation 6.07 |
Comparison: Total Cholesterol at Week 26.p-value: 0.073595% CI: [-0.5, 10.91]ANCOVA
Comparison: HDL-c at Week 26.p-value: 0.001795% CI: [0.79, 3.39]ANCOVA
Comparison: LDL-c at Week 26.p-value: 0.136995% CI: [-1.1, 7.96]ANCOVA
Comparison: Triglycerides at Week 26.p-value: 0.568495% CI: [-10.4, 18.92]ANCOVA
Secondary
Change From Baseline in Mean Standard Deviation (SD) of 24-Hour Glucose Values Measured by CGMS at Week 26
SD of 24-Hour CGMS glucose lab value obtained using the Medtronic MiniMed CGMS. Not all subjects were offered the opportunity to participate in this assessment. Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS-CGMS=all subjects with at least 1 study drug dose, at least 1 post-baseline measurement, and who participated in a 24-hour CGMS substudy. LOCF imputed missing data with any post-baseline visit. Number of subjects who participated in the substudy with 24-hour CGMS values at Baseline and Week 26: inhaled human insulin n=2, insulin glargine n=8.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Mean Standard Deviation (SD) of 24-Hour Glucose Values Measured by CGMS at Week 26 | -12.50 mg/dL | Standard Deviation 2.55 |
| Insulin Glargine | Change From Baseline in Mean Standard Deviation (SD) of 24-Hour Glucose Values Measured by CGMS at Week 26 | 4.46 mg/dL | Standard Deviation 11.51 |
p-value: 0.186295% CI: [-51.34, 13.89]ANCOVA
Secondary
Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26
Post-prandial=after a meal. 8-point scale: (1 = before breakfast, 2 = 2 hours post breakfast, 3 = before lunch, 4 = 2 hours post lunch, 5 = before dinner, 6 = 2 hours post dinner, 7 = at bedtime, 8 = overnight \[between 2 and 4 am\]). Postprandial blood glucose lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS = all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with postprandial blood glucose measurements as measured by 8-point profiles at Baseline and Week 26: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-Breakfast, Week 26 (n=185,171) | -86.61 mg/dL | Standard Deviation 85.98 |
| Inhaled Human Insulin | Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-Lunch, Week 26 (n=184, 172) | -86.66 mg/dL | Standard Deviation 77.49 |
| Inhaled Human Insulin | Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-Dinner, Week 26 (n=187,166) | -81.86 mg/dL | Standard Deviation 75.94 |
| Insulin Glargine | Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-Breakfast, Week 26 (n=185,171) | -75.36 mg/dL | Standard Deviation 79.04 |
| Insulin Glargine | Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-Lunch, Week 26 (n=184, 172) | -58.51 mg/dL | Standard Deviation 86.93 |
| Insulin Glargine | Change From Baseline in Postprandial Blood Glucose as Measured by 8-Point Profiles at Week 26 | Post-Dinner, Week 26 (n=187,166) | -59.20 mg/dL | Standard Deviation 86.21 |
Comparison: Post-Breakfast, Week 26.p-value: 0.120795% CI: [-21.76, 2.54]ANCOVA
Comparison: Post-Lunch, Week 26.p-value: <0.000195% CI: [-39.77, -18.44]ANCOVA
Comparison: Post-Dinner, Week 26.p-value: <0.000195% CI: [-44.17, -23.35]ANCOVA
Secondary
Crude Hypoglycemic Event Rate
crude event rate=(events)/(subject-months). Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe.
Time frame: Months 1 to 7
Population: Safety population=all subjects who took at least 1 dose of study drug. Number of subjects with at least 1 hypoglycemic event during the course of the study that were evaluable at the specified month: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 2 (n=141, 81) | 2.6 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 4 (n=120, 80) | 0 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 1 (n=147, 83) | 1.3 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 5 (n=117, 79) | 1.4 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 2 (n=141, 81) | 0.7 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 5 (n=117, 79) | 1.4 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 1 (n=147, 83) | 0 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 5 (n=117, 79) | 0 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 3 (n=135, 81) | 2.2 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 6 (n=109, 77) | 1.2 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 3 (n=135, 81) | 2.3 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 6 (n=109, 77) | 1.2 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 3 (n=135, 81) | 2.3 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 6 (n=109, 77) | 0 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 2 (n=141, 81) | 2.6 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 7 (n=77, 60) | 0.9 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Overall at Month 4 (n=120, 80) | 1.4 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 7 (n=77, 60) | 0.9 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 1 (n=147, 83) | 1.3 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Severe at Month 7 (n=77, 60) | 0 events / subject-months |
| Inhaled Human Insulin | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 4 (n=120, 80) | 1.4 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 7 (n=77, 60) | 0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 1 (n=147, 83) | 0.5 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 1 (n=147, 83) | 0.5 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 1 (n=147, 83) | 0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 2 (n=141, 81) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 2 (n=141, 81) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 3 (n=135, 81) | 1.0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 3 (n=135, 81) | 1.0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 3 (n=135, 81) | 0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 4 (n=120, 80) | 0.6 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 4 (n=120, 80) | 0.6 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 4 (n=120, 80) | 0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 5 (n=117, 79) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 5 (n=117, 79) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 5 (n=117, 79) | 0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 6 (n=109, 77) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 6 (n=109, 77) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 6 (n=109, 77) | 0 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Overall at Month 7 (n=77, 60) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Mild/Moderate at Month 7 (n=77, 60) | 0.8 events / subject-months |
| Insulin Glargine | Crude Hypoglycemic Event Rate | Severe at Month 2 (n=141, 81) | 0 events / subject-months |
Secondary
Number of Nocturnal Hypoglycemic Events
A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Nocturnal hypoglycemia=event occuring from midnight to 5:59 am.
Time frame: Months 1 to 7
Population: Safety population=all subjects who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Human Insulin | Number of Nocturnal Hypoglycemic Events | 187 events |
| Insulin Glargine | Number of Nocturnal Hypoglycemic Events | 114 events |
Secondary
Number of Subjects With Hypoglycemic Events
A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. An event was severe if the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe.
Time frame: Months 1 to 7
Population: Safety population=all subjects who took at least 1 dose of study drug. Number of subjects with at least 1 hypoglycemic event during the course of the study that were evaluable at the specified month: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 1 (n=147, 83) | 0 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 4 (n=120, 80) | 0 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 2 (n=141, 81) | 1 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 5 (n=117, 79) | 55 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 1 (n=147, 83) | 69 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 5 (n=117, 79) | 55 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 3 (n=135, 81) | 84 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 5 (n=117, 79) | 0 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 2 (n=141, 81) | 98 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 6 (n=109, 77) | 42 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 3 (n=135, 81) | 83 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 6 (n=109, 77) | 42 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 1 (n=147, 83) | 70 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 6 (n=109, 77) | 0 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 3 (n=135, 81) | 3 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 7 (n=77, 60) | 8 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 2 (n=141, 81) | 98 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 7 (n=77, 60) | 8 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Overall at Month 4 (n=120, 80) | 61 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Severe at Month 7 (n=77, 60) | 0 participants |
| Inhaled Human Insulin | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 4 (n=120, 80) | 61 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 7 (n=77, 60) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 1 (n=147, 83) | 24 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 1 (n=147, 83) | 24 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 1 (n=147, 83) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 2 (n=141, 81) | 38 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 2 (n=141, 81) | 38 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 2 (n=141, 81) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 3 (n=135, 81) | 35 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 3 (n=135, 81) | 35 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 3 (n=135, 81) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 4 (n=120, 80) | 25 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 4 (n=120, 80) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 5 (n=117, 79) | 30 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 5 (n=117, 79) | 30 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 5 (n=117, 79) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 6 (n=109, 77) | 31 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 6 (n=109, 77) | 31 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Severe at Month 6 (n=109, 77) | 0 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 7 (n=77, 60) | 4 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Mild/Moderate at Month 7 (n=77, 60) | 4 participants |
| Insulin Glargine | Number of Subjects With Hypoglycemic Events | Overall at Month 4 (n=120, 80) | 25 participants |
Secondary
Number of Total Hypoglycemic Events
A hypoglycemic event was identified by characteristic symptoms or blood glucose levels. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe. Total=events during the study.
Time frame: Months 1 to 7
Population: Safety population=all subjects who took at least 1 dose of study drug. Number of subjects with at least 1 hypoglycemic event during the course of the study that were evaluable at the specified month: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 4 (n=120, 80) | 166 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 4 (n=120, 80) | 0 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 2 (n=141, 81) | 365 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 5 (n=117, 79) | 157 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 1 (n=147, 83) | 195 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 5 (n=117, 79) | 157 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 2 (n=141, 81) | 364 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 5 (n=117, 79) | 0 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 3 (n=135, 81) | 3 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 6 (n=109, 77) | 119 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 2 (n=141, 81) | 1 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 6 (n=109, 77) | 119 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 1 (n=147, 83) | 194 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 6 (n=109, 77) | 0 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 3 (n=135, 81) | 292 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Overall at Month 7 (n=77, 60) | 12 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 4 (n=120, 80) | 166 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 7 (n=77, 60) | 12 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Mild/Moderate at Month 3 (n=135, 81) | 289 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 7 (n=77, 60) | 0 events |
| Inhaled Human Insulin | Number of Total Hypoglycemic Events | Severe at Month 1 (n=147, 83) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 7 (n=77, 60) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 3 (n=135, 81) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 1 (n=147, 83) | 41 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 1 (n=147, 83) | 41 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 1 (n=147, 83) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 2 (n=141, 81) | 66 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 2 (n=141, 81) | 66 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 2 (n=141, 81) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 3 (n=135, 81) | 84 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 3 (n=135, 81) | 84 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 4 (n=120, 80) | 51 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 4 (n=120, 80) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 5 (n=117, 79) | 64 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 5 (n=117, 79) | 64 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 5 (n=117, 79) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 6 (n=109, 77) | 63 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 6 (n=109, 77) | 63 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Severe at Month 6 (n=109, 77) | 0 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 7 (n=77, 60) | 5 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Mild/Moderate at Month 7 (n=77, 60) | 5 events |
| Insulin Glargine | Number of Total Hypoglycemic Events | Overall at Month 4 (n=120, 80) | 51 events |
Secondary
Number of Total Subject Months of Treatment
Number of total subject months of treatment. Subject months = number of days from start of treatment to the last day of active treatment + 1 day lag, including off-drug time)/30.44. Severe=the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of \< = 49 mg/dL. Events not meeting all 3 criteria were considered mild-moderate. Overall=mild, moderate, and severe.
Time frame: Months 1 to 7
Population: Safety population=all subjects who took at least 1 dose of study drug. Number of subjects with at least 1 hypoglycemic event during the course of the study that were evaluable at the specified month: n=inhaled human insulin, insulin glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 1 (n=147, 83) | 145.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 1 (n=147, 83) | 145.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 1 (n=147, 83) | 145.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 2 (n=141, 81) | 138.3 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 2 (n=141, 81) | 138.3 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 2 (n=141, 81) | 138.3 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 3 (n=135, 81) | 128.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 3 (n=135, 81) | 128.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 3 (n=135, 81) | 128.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 4 (n=120, 80) | 117.7 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 4 (n=120, 80) | 117.7 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 4 (n=120, 80) | 117.7 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 5 (n=117, 79) | 112.2 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 5 (n=117, 79) | 112.2 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 5 (n=117, 79) | 112.2 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 6 (n=109, 77) | 103.5 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 6 (n=109, 77) | 103.5 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 6 (n=109, 77) | 103.5 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Overall at Month 7 (n=77, 60) | 12.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Mild/Moderate at Month 7 (n=77, 60) | 12.8 subject months |
| Inhaled Human Insulin | Number of Total Subject Months of Treatment | Severe at Month 7 (n=77, 60) | 12.8 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 4 (n=120, 80) | 79.7 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 1 (n=147, 83) | 82.4 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 7 (n=77, 60) | 6.6 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 1 (n=147, 83) | 82.4 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 4 (n=120, 80) | 79.7 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 1 (n=147, 83) | 82.4 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 6 (n=109, 77) | 75.7 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 2 (n=141, 81) | 81.0 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 5 (n=117, 79) | 77.9 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 2 (n=141, 81) | 81.0 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 7 (n=77, 60) | 6.6 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 2 (n=141, 81) | 81.0 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 5 (n=117, 79) | 77.9 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 3 (n=135, 81) | 80.4 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 6 (n=109, 77) | 75.7 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 3 (n=135, 81) | 80.4 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 5 (n=117, 79) | 77.9 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Severe at Month 3 (n=135, 81) | 80.4 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Mild/Moderate at Month 7 (n=77, 60) | 6.6 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 4 (n=120, 80) | 79.7 subject months |
| Insulin Glargine | Number of Total Subject Months of Treatment | Overall at Month 6 (n=109, 77) | 75.7 subject months |
Secondary
Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26
Percentage of subjects with glycosylated hemoglobin A1c lab value less than 6.5%.
Time frame: Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with HbA1c \< 6.5% at Week 26: inhaled human insulin n=72, insulin glargine n=42.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Human Insulin | Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26 | 35.5 percentage of participants |
| Insulin Glargine | Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26 | 22.2 percentage of participants |
p-value: 0.005295% CI: [1.22, 3.14]Regression, Logistic
Secondary
Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26
Percentage of subjects with glycosylated hemoglobin A1c lab value less than 7.0%.
Time frame: Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with HbA1c \< 7.0% at Week 26: inhaled human insulin n=127, insulin glargine n=90.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Human Insulin | Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26 | 62.6 percentage of participants |
| Insulin Glargine | Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26 | 47.6 percentage of participants |
p-value: 0.002295% CI: [1.29, 3.15]Regression, Logistic
Secondary
Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26
Number of subjects with glycosylated hemoglobin A1c lab value less than 8.0%.
Time frame: Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Number of subjects with HbA1c \< 8.0% at Week 26: inhaled human insulin n=162, insulin glargine n=158.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Human Insulin | Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26 | 79.8 percentage of participants |
| Insulin Glargine | Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26 | 83.6 percentage of participants |
p-value: 0.24895% CI: [0.4, 1.27]Regression, Logistic
Other Pre-specified
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the FAS
HbA1c lab value: Change = value at Week 26 minus value at Baseline.
Time frame: Baseline, Week 26
Population: FAS=all subjects who took at least 1 dose of study drug and had at least 1 post-baseline measurement. LOCF imputed missing data with any post-baseline visit. Using the FAS yielded supplemental analyses for the primary efficacy endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Human Insulin | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the FAS | -1.91 percent | Standard Deviation 1.41 |
| Insulin Glargine | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the FAS | -1.67 percent | Standard Deviation 1.38 |
Comparison: The null hypothesis was that the inhaled human insulin group was inferior to the insulin glargine group with respect to 26-week change from baseline in HbA1c, while the alternate hypothesis is that the inhaled human insulin group was not inferior to the insulin glargine group with respect to 26-week change from baseline in HbA1c, given the predetermined non-inferiority margin of 0.4%.p-value: <0.000195% CI: [-0.47, -0.08]ANCOVA
Comparison: With an established non-inferiority claim, an additional test for superiority was conducted (ie, the margin was 0.0%).p-value: 0.006295% CI: [-0.47, -0.08]ANCOVA