Trial Outcomes & Findings for This Study Is To Determine If Inhaled Insulin Is Effective In Treating Type 2 Diabetes Mellitus (NCT NCT00418522)
NCT ID: NCT00418522
Last Updated: 2018-09-28
Results Overview
HbA1c lab value: Change = value at Week 26 minus value at Baseline.
COMPLETED
PHASE4
413 participants
Baseline, Week 26
2018-09-28
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
219
|
194
|
|
Overall Study
Received Treatment
|
212
|
190
|
|
Overall Study
COMPLETED
|
136
|
152
|
|
Overall Study
NOT COMPLETED
|
83
|
42
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
7
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
3
|
|
Overall Study
Lost to Follow-up
|
10
|
4
|
|
Overall Study
Withdrawal by Subject
|
31
|
7
|
|
Overall Study
Other
|
27
|
23
|
|
Overall Study
Randomized but did not receive treatment
|
7
|
4
|
Baseline Characteristics
This Study Is To Determine If Inhaled Insulin Is Effective In Treating Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Inhaled Human Insulin
n=212 Participants
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.
|
Insulin Glargine
n=190 Participants
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.
|
Total
n=402 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to 44 years
|
27 participants
n=5 Participants
|
26 participants
n=7 Participants
|
53 participants
n=5 Participants
|
|
Age, Customized
45 to 65 years
|
151 participants
n=5 Participants
|
125 participants
n=7 Participants
|
276 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
34 participants
n=5 Participants
|
39 participants
n=7 Participants
|
73 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
176 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
120 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
226 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 26Population: 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.
HbA1c lab value: Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=154 Participants
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.
|
Insulin Glargine
n=157 Participants
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.
|
|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the Per Protocol (PP) Population
|
-2.01 percent
Standard Deviation 1.39
|
-1.75 percent
Standard Deviation 1.40
|
SECONDARY outcome
Timeframe: Week 26Population: 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.
Percentage of subjects with glycosylated hemoglobin A1c lab value less than 6.5%.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Percentage of Subjects Achieving Glycemic Control (HbA1c < 6.5%) at Week 26
|
35.5 percentage of participants
|
22.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 26Population: 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.
Percentage of subjects with glycosylated hemoglobin A1c lab value less than 7.0%.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Percentage of Subjects Achieving Glycemic Control (HbA1c < 7.0%) at Week 26
|
62.6 percentage of participants
|
47.6 percentage of participants
|
SECONDARY outcome
Timeframe: Week 26Population: 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.
Number of subjects with glycosylated hemoglobin A1c lab value less than 8.0%.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Percentage of Subjects Achieving Glycemic Control (HbA1c < 8.0%) at Week 26
|
79.8 percentage of participants
|
83.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Fasting plasma glucose lab value: Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose at Week 26
|
-52.77 mg/dL
Standard Deviation 69.48
|
-53.50 mg/dL
Standard Deviation 62.92
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
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
|
-61.16 mg/dL
Standard Deviation 54.68
|
|
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
|
-66.02 mg/dL
Standard Deviation 62.32
|
|
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
|
-64.77 mg/dL
Standard Deviation 64.47
|
|
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
|
-58.85 mg/dL
Standard Deviation 64.58
|
|
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
|
-54.89 mg/dL
Standard Deviation 63.02
|
|
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
|
-51.27 mg/dL
Standard Deviation 59.92
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
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
|
-75.36 mg/dL
Standard Deviation 79.04
|
|
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
|
-58.51 mg/dL
Standard Deviation 86.93
|
|
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
|
-59.20 mg/dL
Standard Deviation 86.21
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Change From Baseline in Lipids at Week 26
Total cholesterol, Week 26 (n=197, 186)
|
-2.80 mg/dL
Standard Deviation 31.97
|
-6.19 mg/dL
Standard Deviation 29.95
|
|
Change From Baseline in Lipids at Week 26
HDL-c, Week 26 (n=197, 186)
|
2.97 mg/dL
Standard Deviation 6.99
|
0.69 mg/dL
Standard Deviation 6.07
|
|
Change From Baseline in Lipids at Week 26
LDL-c, Week 26 (n=197, 186)
|
-2.09 mg/dL
Standard Deviation 25.74
|
-3.71 mg/dL
Standard Deviation 23.63
|
|
Change From Baseline in Lipids at Week 26
Triglycerides, Week 26 (n=197, 187)
|
-42.65 mg/dL
Standard Deviation 87.70
|
-46.23 mg/dL
Standard Deviation 147.8
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
CV biomarker (hs-CRP, Leptin, and Spot Urine Microalbumin) lab value: Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
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
|
0.32 mg/L
Standard Deviation 3.69
|
|
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 13.50
|
4.41 mg/L
Standard Deviation 10.50
|
|
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
|
3.70 mg/L
Standard Deviation 54.53
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
CV biomarker (adiponectin and ApoB) lab value: Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
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
|
-0.32 mg/mL
Standard Deviation 5.15
|
|
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
|
-0.06 mg/mL
Standard Deviation 0.17
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Change From Baseline in 24-Hour Continuous Glucose Monitoring System (CGMS) Glucose Values at Week 26
|
-36.53 mg/dL
Standard Deviation 33.96
|
-35.63 mg/dL
Standard Deviation 58.19
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
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
|
4.46 mg/dL
Standard Deviation 11.51
|
SECONDARY outcome
Timeframe: Months 1 to 7Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=212 Participants
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.
|
Insulin Glargine
n=190 Participants
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.
|
|---|---|---|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 5 (n=117, 79)
|
55 participants
|
30 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 5 (n=117, 79)
|
0 participants
|
0 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 1 (n=147, 83)
|
70 participants
|
24 participants
|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 1 (n=147, 83)
|
69 participants
|
24 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 1 (n=147, 83)
|
0 participants
|
0 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 2 (n=141, 81)
|
98 participants
|
38 participants
|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 2 (n=141, 81)
|
98 participants
|
38 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 2 (n=141, 81)
|
1 participants
|
0 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 3 (n=135, 81)
|
84 participants
|
35 participants
|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 3 (n=135, 81)
|
83 participants
|
35 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 3 (n=135, 81)
|
3 participants
|
0 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 4 (n=120, 80)
|
61 participants
|
25 participants
|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 4 (n=120, 80)
|
61 participants
|
25 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 4 (n=120, 80)
|
0 participants
|
0 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 5 (n=117, 79)
|
55 participants
|
30 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 6 (n=109, 77)
|
42 participants
|
31 participants
|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 6 (n=109, 77)
|
42 participants
|
31 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 6 (n=109, 77)
|
0 participants
|
0 participants
|
|
Number of Subjects With Hypoglycemic Events
Overall at Month 7 (n=77, 60)
|
8 participants
|
4 participants
|
|
Number of Subjects With Hypoglycemic Events
Mild/Moderate at Month 7 (n=77, 60)
|
8 participants
|
4 participants
|
|
Number of Subjects With Hypoglycemic Events
Severe at Month 7 (n=77, 60)
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Months 1 to 7Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=212 Participants
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.
|
Insulin Glargine
n=190 Participants
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.
|
|---|---|---|
|
Number of Total Hypoglycemic Events
Overall at Month 1 (n=147, 83)
|
195 events
|
41 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 1 (n=147, 83)
|
194 events
|
41 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 1 (n=147, 83)
|
0 events
|
0 events
|
|
Number of Total Hypoglycemic Events
Overall at Month 2 (n=141, 81)
|
365 events
|
66 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 2 (n=141, 81)
|
364 events
|
66 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 2 (n=141, 81)
|
1 events
|
0 events
|
|
Number of Total Hypoglycemic Events
Overall at Month 3 (n=135, 81)
|
292 events
|
84 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 3 (n=135, 81)
|
289 events
|
84 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 3 (n=135, 81)
|
3 events
|
0 events
|
|
Number of Total Hypoglycemic Events
Overall at Month 4 (n=120, 80)
|
166 events
|
51 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 4 (n=120, 80)
|
166 events
|
51 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 4 (n=120, 80)
|
0 events
|
0 events
|
|
Number of Total Hypoglycemic Events
Overall at Month 5 (n=117, 79)
|
157 events
|
64 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 5 (n=117, 79)
|
157 events
|
64 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 5 (n=117, 79)
|
0 events
|
0 events
|
|
Number of Total Hypoglycemic Events
Overall at Month 6 (n=109, 77)
|
119 events
|
63 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 6 (n=109, 77)
|
119 events
|
63 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 6 (n=109, 77)
|
0 events
|
0 events
|
|
Number of Total Hypoglycemic Events
Overall at Month 7 (n=77, 60)
|
12 events
|
5 events
|
|
Number of Total Hypoglycemic Events
Mild/Moderate at Month 7 (n=77, 60)
|
12 events
|
5 events
|
|
Number of Total Hypoglycemic Events
Severe at Month 7 (n=77, 60)
|
0 events
|
0 events
|
SECONDARY outcome
Timeframe: Months 1 to 7Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=212 Participants
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.
|
Insulin Glargine
n=190 Participants
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.
|
|---|---|---|
|
Number of Total Subject Months of Treatment
Overall at Month 1 (n=147, 83)
|
145.8 subject months
|
82.4 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 1 (n=147, 83)
|
145.8 subject months
|
82.4 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 1 (n=147, 83)
|
145.8 subject months
|
82.4 subject months
|
|
Number of Total Subject Months of Treatment
Overall at Month 2 (n=141, 81)
|
138.3 subject months
|
81.0 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 2 (n=141, 81)
|
138.3 subject months
|
81.0 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 2 (n=141, 81)
|
138.3 subject months
|
81.0 subject months
|
|
Number of Total Subject Months of Treatment
Overall at Month 3 (n=135, 81)
|
128.8 subject months
|
80.4 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 3 (n=135, 81)
|
128.8 subject months
|
80.4 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 3 (n=135, 81)
|
128.8 subject months
|
80.4 subject months
|
|
Number of Total Subject Months of Treatment
Overall at Month 4 (n=120, 80)
|
117.7 subject months
|
79.7 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 4 (n=120, 80)
|
117.7 subject months
|
79.7 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 4 (n=120, 80)
|
117.7 subject months
|
79.7 subject months
|
|
Number of Total Subject Months of Treatment
Overall at Month 5 (n=117, 79)
|
112.2 subject months
|
77.9 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 5 (n=117, 79)
|
112.2 subject months
|
77.9 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 5 (n=117, 79)
|
112.2 subject months
|
77.9 subject months
|
|
Number of Total Subject Months of Treatment
Overall at Month 6 (n=109, 77)
|
103.5 subject months
|
75.7 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 6 (n=109, 77)
|
103.5 subject months
|
75.7 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 6 (n=109, 77)
|
103.5 subject months
|
75.7 subject months
|
|
Number of Total Subject Months of Treatment
Overall at Month 7 (n=77, 60)
|
12.8 subject months
|
6.6 subject months
|
|
Number of Total Subject Months of Treatment
Mild/Moderate at Month 7 (n=77, 60)
|
12.8 subject months
|
6.6 subject months
|
|
Number of Total Subject Months of Treatment
Severe at Month 7 (n=77, 60)
|
12.8 subject months
|
6.6 subject months
|
SECONDARY outcome
Timeframe: Months 1 to 7Population: 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.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=212 Participants
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.
|
Insulin Glargine
n=190 Participants
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.
|
|---|---|---|
|
Crude Hypoglycemic Event Rate
Overall at Month 1 (n=147, 83)
|
1.3 events / subject-months
|
0.5 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 1 (n=147, 83)
|
1.3 events / subject-months
|
0.5 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 1 (n=147, 83)
|
0 events / subject-months
|
0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Overall at Month 2 (n=141, 81)
|
2.6 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 2 (n=141, 81)
|
2.6 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 2 (n=141, 81)
|
0.7 events / subject-months
|
0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Overall at Month 3 (n=135, 81)
|
2.3 events / subject-months
|
1.0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 3 (n=135, 81)
|
2.2 events / subject-months
|
1.0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 3 (n=135, 81)
|
2.3 events / subject-months
|
0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Overall at Month 4 (n=120, 80)
|
1.4 events / subject-months
|
0.6 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 4 (n=120, 80)
|
1.4 events / subject-months
|
0.6 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 4 (n=120, 80)
|
0 events / subject-months
|
0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Overall at Month 5 (n=117, 79)
|
1.4 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 5 (n=117, 79)
|
1.4 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 5 (n=117, 79)
|
0 events / subject-months
|
0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Overall at Month 6 (n=109, 77)
|
1.2 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 6 (n=109, 77)
|
1.2 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 6 (n=109, 77)
|
0 events / subject-months
|
0 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Overall at Month 7 (n=77, 60)
|
0.9 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Mild/Moderate at Month 7 (n=77, 60)
|
0.9 events / subject-months
|
0.8 events / subject-months
|
|
Crude Hypoglycemic Event Rate
Severe at Month 7 (n=77, 60)
|
0 events / subject-months
|
0 events / subject-months
|
SECONDARY outcome
Timeframe: Months 1 to 7Population: Safety population=all subjects who took at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Inhaled Human Insulin
n=212 Participants
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.
|
Insulin Glargine
n=190 Participants
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.
|
|---|---|---|
|
Number of Nocturnal Hypoglycemic Events
|
187 events
|
114 events
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Body weight value: Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Change From Baseline in Body Weight at Week 26
|
3.55 kg
Standard Deviation 4.74
|
2.33 kg
Standard Deviation 3.80
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
BMI value (kg/m2): Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Change From Baseline in Body Mass Index (BMI) at Week 26
|
1.22 kg/m2
Standard Deviation 1.66
|
0.80 kg/m2
Standard Deviation 1.30
|
SECONDARY outcome
Timeframe: Baseline, Week 26Due 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 26Population: 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.
HbA1c lab value: Change = value at Week 26 minus value at Baseline.
Outcome measures
| Measure |
Inhaled Human Insulin
n=203 Participants
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.
|
Insulin Glargine
n=189 Participants
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.
|
|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at Week 26 for the FAS
|
-1.91 percent
Standard Deviation 1.41
|
-1.67 percent
Standard Deviation 1.38
|
Adverse Events
Inhaled Human Insulin
Insulin Glargine
Serious adverse events
| Measure |
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.
|
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.
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.47%
1/212
|
0.53%
1/190
|
|
Cardiac disorders
Angina unstable
|
0.47%
1/212
|
0.00%
0/190
|
|
Cardiac disorders
Cardiovascular disorder
|
0.00%
0/212
|
0.53%
1/190
|
|
Cardiac disorders
Palpitations
|
0.47%
1/212
|
0.00%
0/190
|
|
Gastrointestinal disorders
Pancreatitis
|
0.94%
2/212
|
0.00%
0/190
|
|
General disorders
Chest pain
|
0.47%
1/212
|
0.00%
0/190
|
|
Infections and infestations
Hepatitis A
|
0.47%
1/212
|
0.00%
0/190
|
|
Infections and infestations
Sepsis
|
0.00%
0/212
|
0.53%
1/190
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.47%
1/212
|
0.00%
0/190
|
|
Nervous system disorders
Transient ischaemic attack
|
0.47%
1/212
|
0.00%
0/190
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.47%
1/212
|
0.00%
0/190
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/212
|
0.53%
1/190
|
Other adverse events
| Measure |
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.
|
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.
|
|---|---|---|
|
Eye disorders
Vision blurred
|
6.6%
14/212
|
3.2%
6/190
|
|
Gastrointestinal disorders
Diarrhoea
|
5.7%
12/212
|
4.2%
8/190
|
|
Gastrointestinal disorders
Nausea
|
9.9%
21/212
|
7.9%
15/190
|
|
General disorders
Asthenia
|
13.2%
28/212
|
8.9%
17/190
|
|
General disorders
Fatigue
|
6.1%
13/212
|
5.8%
11/190
|
|
General disorders
Injection site haematoma
|
0.00%
0/212
|
6.8%
13/190
|
|
General disorders
Oedema peripheral
|
5.2%
11/212
|
4.7%
9/190
|
|
Infections and infestations
Influenza
|
4.2%
9/212
|
5.3%
10/190
|
|
Infections and infestations
Nasopharyngitis
|
5.7%
12/212
|
6.8%
13/190
|
|
Infections and infestations
Upper respiratory tract infection
|
10.8%
23/212
|
15.3%
29/190
|
|
Investigations
Weight increased
|
8.0%
17/212
|
4.7%
9/190
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
67.9%
144/212
|
43.7%
83/190
|
|
Nervous system disorders
Dizziness
|
18.9%
40/212
|
15.3%
29/190
|
|
Nervous system disorders
Headache
|
13.7%
29/212
|
8.9%
17/190
|
|
Nervous system disorders
Tremor
|
31.6%
67/212
|
22.6%
43/190
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.5%
18/212
|
3.2%
6/190
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
16.5%
35/212
|
11.1%
21/190
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER