Trial Outcomes & Findings for A Clinical Trial Comparing the Efficacy and Safety of Exubera® and Lantus® (NCT NCT00391027)
NCT ID: NCT00391027
Last Updated: 2015-07-23
Results Overview
Change (measured as percent): HbA1c at observation minus HbA1c at baseline. Primary objective to demonstrate non-inferiority of inhaled insulin compared to insulin glargine for glycemic control after 26 weeks of treatment not attainable due to early termination of study; analyses were descriptive and graphical.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
261 participants
Primary outcome timeframe
Baseline, Week 26
Results posted on
2015-07-23
Participant Flow
Number of subjects randomized = 261; number of subjects treated (out of 261 randomized) = 257.
Participant milestones
| Measure |
Inhaled Human Insulin (Exubera®)
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Overall Study
STARTED
|
135
|
122
|
|
Overall Study
COMPLETED
|
110
|
110
|
|
Overall Study
NOT COMPLETED
|
25
|
12
|
Reasons for withdrawal
| Measure |
Inhaled Human Insulin (Exubera®)
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Overall Study
Adverse Event
|
8
|
8
|
|
Overall Study
Lack of Efficacy
|
3
|
0
|
|
Overall Study
Withdrawal by Subject
|
10
|
1
|
|
Overall Study
Other
|
4
|
3
|
Baseline Characteristics
A Clinical Trial Comparing the Efficacy and Safety of Exubera® and Lantus®
Baseline characteristics by cohort
| Measure |
Inhaled Human Insulin (Exubera®)
n=135 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=122 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
Total
n=257 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 - 44 years
|
8 participants
n=5 Participants
|
3 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Age, Customized
45 - 64 years
|
78 participants
n=5 Participants
|
71 participants
n=7 Participants
|
149 participants
n=5 Participants
|
|
Age, Customized
> = 65 years
|
49 participants
n=5 Participants
|
48 participants
n=7 Participants
|
97 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
54 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
81 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
152 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 26Population: Full analysis set (FAS) all randomized subjects with at least 1 dose of study medication, baseline and post-baseline HbA1c measurement. Last observation carried forward (LOCF).
Change (measured as percent): HbA1c at observation minus HbA1c at baseline. Primary objective to demonstrate non-inferiority of inhaled insulin compared to insulin glargine for glycemic control after 26 weeks of treatment not attainable due to early termination of study; analyses were descriptive and graphical.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
|
-1.7 percent
Standard Deviation 1.19
|
-1.4 percent
Standard Deviation 1.14
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, and Week 18Population: FAS; LOCF; (n) = number of subjects with analyzable data at observation for inhaled insulin and insulin glargine, respectively.
Change (measured as percent) from baseline calculated as HbA1c at observation minus HbA1c at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in HbA1c Prior to Week 26
Week 12 (n = 134, 121)
|
-1.6 percent
Standard Deviation 1.08
|
-1.3 percent
Standard Deviation 0.99
|
|
Change From Baseline in HbA1c Prior to Week 26
Week 2 (n = 128, 108)
|
-0.4 percent
Standard Deviation 0.40
|
-0.3 percent
Standard Deviation 0.40
|
|
Change From Baseline in HbA1c Prior to Week 26
Week 4 (n = 134, 121)
|
-0.8 percent
Standard Deviation 0.61
|
-0.6 percent
Standard Deviation 0.58
|
|
Change From Baseline in HbA1c Prior to Week 26
Week 8 (n = 134, 121)
|
-1.3 percent
Standard Deviation 0.86
|
-1.1 percent
Standard Deviation 0.85
|
|
Change From Baseline in HbA1c Prior to Week 26
Week 18 (n = 134, 121)
|
-1.7 percent
Standard Deviation 1.16
|
-1.5 percent
Standard Deviation 1.11
|
SECONDARY outcome
Timeframe: Week 26Population: FAS
Number of subjects with glycemic control HbA1c measurement of \< 6.5 % at observation.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Number of Subjects With HbA1c < 6.5 %
|
37 participants
|
23 participants
|
SECONDARY outcome
Timeframe: Week 26Population: FAS
Number of subjects with glycemic control HbA1c measurement of \< 7.0 % at observation.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Number of Subjects With HbA1c < 7.0 %
|
84 participants
|
67 participants
|
SECONDARY outcome
Timeframe: Week 26Population: FAS
Number of subjects with glycemic control HbA1c measurement of \< 8.0 % at observation.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Number of Subjects With HbA1c < 8.0 %
|
121 participants
|
108 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
FPG measured as milligrams/deciliter (mg/dl). Change from baseline calculated as FPG at observation minus FPG at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=120 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) Level
|
-30.6 mg/dl
Standard Deviation 49.04
|
-60.1 mg/dl
Standard Deviation 51.95
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF; (n) = number of subjects with analyzable data at observation for inhaled insulin and insulin glargine, respectively.
Blood glucose (BG) self-monitored by subject at home; measured at least once between Visits 2, 3 and between Visits 8, 9 (8-point: fasting, pre-meal, post-meal, bedtime, 2:00 am); between each visit: Visit 3 to 8 (7-point: fasting, post-meal, pre-lunch, pre-dinner, bedtime). Post-meal: 2-hour period after breakfast, lunch, dinner. Change: average overall absolute, pre-meal, and post-meal blood glucose = HBGM at observation minus HBGM at baseline; pre-meal to post-meal blood glucose = HBGM at post-meal minus HBGM at pre-meal.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point)
Average overall absolute BG (n=101, 95)
|
-45.0 mg/dl
Standard Deviation 46.26
|
-43.7 mg/dl
Standard Deviation 48.41
|
|
Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point)
Average pre-meal BG (n=101, 95)
|
-38.1 mg/dl
Standard Deviation 43.24
|
-50.7 mg/dl
Standard Deviation 47.54
|
|
Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point)
Average post-meal BG (n=99, 91)
|
-64.5 mg/dl
Standard Deviation 59.35
|
-49.6 mg/dl
Standard Deviation 58.33
|
|
Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point)
Change from pre-meal to post-meal BG (n=99, 91)
|
-24.5 mg/dl
Standard Deviation 35.28
|
1.6 mg/dl
Standard Deviation 39.82
|
SECONDARY outcome
Timeframe: Week 26Population: FAS
Number of subjects with hypoglycemic events by severity. Severe hypoglycemia: subject unable to treat self; exhibits a neurological symptom; and blood glucose \<=2.72 mmol/L or blood glucose not measured but symptoms reversed with food intake, SC glucagon, or intravenous glucose. If all 3 criteria not met, hypoglycemia defined as mild or moderate.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Number of Subjects With Hypoglycemic Events by Severity
Week 26 Mild, Moderate
|
26 participants
|
32 participants
|
|
Number of Subjects With Hypoglycemic Events by Severity
Week 26 Severe
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Week 26Population: FAS
Number of events of nocturnal hypoglycemia, incidence: midnight to 6:00 am. Hypoglycemia: characteristic symptoms of hypoglycemia with no blood glucose check; resolved with food intake, SC glucagon, or intravenous (IV) glucose; or symptoms with glucose \<3.27 mmol/L (59 mg/dL); or any glucose measurement \<=2.72 mmol/L (49 mg/dl). Severity of nocturnal glycemia not summarized.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Number of Events of Nocturnal Hypoglycemia
|
159 events
|
81 events
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
Change from baseline calculated as body weight at observation minus body weight at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=125 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=118 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in Body Weight
|
2.2 kilograms (kg)
Standard Deviation 3.57
|
1.1 kilograms (kg)
Standard Deviation 3.43
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
BMI measured as kilograms per meter squared (kg/m2). Change calculated as BMI at observation minus BMI at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=125 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=118 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in Body Mass Index (BMI)
|
0.7 kg/m2
Standard Deviation 1.24
|
0.4 kg/m2
Standard Deviation 1.20
|
SECONDARY outcome
Timeframe: Week 26Population: Safety population: all subjects who received at least 1 dose of study medication.
Number of subjects discontinued due to signs and symptoms of persistent hyperglycemia or HbA1c \> 12.0 % or frequent and unexplained severe hypoglycemic events (\> 3 events per month for 2 or more months); subject's HbA1c not \< = 7 % at Week 12.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=135 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=122 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Number of Subjects Discontinued Due to Insufficient Clinical Response
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Week 26Subject reported outcomes for Diabetes Treatment Satisfaction Questionnaire-Status (DTSQs), DTSQ-change, Patient Satisfaction with Insulin Therapy-16 item, Mental Health Inventory-17 item, and Euro Quality of life 5-Dimensions (EuroQol 5-D) Questionnaire not summarized due to cancellation of Exubera® program.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; (n) = number of subjects with analyzable data at observation for inhaled insulin and insulin glargine, respectively. Revised table rectifies a programming code error that was determined post-Clinical study report (CSR) approval.
The mean of the 24-hour mean and the mean of the 24-hour standard deviation (SD) (variability around the average glucose concentration) calculated on glucose values (mg/dl) collected during inpatient evaluation of glycemic stability. Interstitial glucose assessed at 5 minute intervals starting pre-supper on Day 1 of evaluation; ending on Day 3 pre-breakfast. Analysis is on data generated between 6:00 am on Day 2 and 6:00 am on Day 3.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=134 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=121 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Continuous Glucose Monitoring System (CGMS) 24-hour Glucose Profile in a Subset of Patients
Week 26: 24-hour mean (n=14, 12)
|
107.6 mg/dl
Standard Deviation 18.46
|
102.1 mg/dl
Standard Deviation 18.02
|
|
Continuous Glucose Monitoring System (CGMS) 24-hour Glucose Profile in a Subset of Patients
Week 26: 24-hour SD (n=14, 12)
|
33.7 mg/dl
Standard Deviation 17.22
|
30.7 mg/dl
Standard Deviation 8.09
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
Change from baseline in CV biomarker hs-CRP (milligrams per deciliter \[mg/dl\]) calculated as hs-CRP at observation minus hs-CRP at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=106 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=98 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in Cardiovascular (CV) Biomarkers - High Sensitive C-reactive Protein (Hs-CRP)
|
0.2 mg/dl
Standard Deviation 1.92
|
-0.1 mg/dl
Standard Deviation 1.56
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
Change from baseline in IL-6 (picograms per milliliter \[pg/ml\]) calculated as IL-6 at observation minus IL-6 at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=55 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=61 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in CV Biomarkers - Interleukin 6 (IL-6)
|
-1.1 pg/ml
Standard Deviation 4.05
|
-2.4 pg/ml
Standard Deviation 10.41
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
Change from baseline in tat-complexes (nanograms per milliliter \[ng/ml\]) calculated as tat-complexes at observation minus tat-complexes at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=31 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=18 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in CV Biomarkers - Thrombin-antithrombin Complexes (Tat-complexes)
|
-3.4 ng/ml
Standard Deviation 10.00
|
-40.4 ng/ml
Standard Deviation 166.90
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS; LOCF.
Change from baseline in soluble tissue factor (pg/ml) calculated as STF at observation minus STF at baseline.
Outcome measures
| Measure |
Inhaled Human Insulin (Exubera®)
n=2 Participants
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=5 Participants
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Change From Baseline in CV Biomarkers - Soluble Tissue Factor (STF)
|
230.2 pg/ml
Standard Deviation 279.92
|
170.4 pg/ml
Standard Deviation 174.07
|
SECONDARY outcome
Timeframe: Baseline, Week 26Urinary free 8-iso prostaglandin F2-alpha (α): compare glucose fluctuations and activation of oxidative stress as assessed by urinary isoprostanes in a subset of subjects randomized to either Exubera® or subcutaneous insulin glargine. The substudy was offered to all subjects. Data not summarized due to cancellation of Exubera® program.
Outcome measures
Outcome data not reported
Adverse Events
Inhaled Human Insulin (Exubera®)
Serious events: 8 serious events
Other events: 105 other events
Deaths: 0 deaths
Insulin Glargine (Lantus®)
Serious events: 10 serious events
Other events: 81 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Inhaled Human Insulin (Exubera®)
n=135 participants at risk
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=122 participants at risk
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/135
|
1.6%
2/122
|
|
Cardiac disorders
Arrhythmia supraventricular
|
0.74%
1/135
|
0.00%
0/122
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/135
|
1.6%
2/122
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/135
|
0.82%
1/122
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.74%
1/135
|
0.00%
0/122
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/135
|
0.82%
1/122
|
|
Cardiac disorders
Myocardial ischaemia
|
0.74%
1/135
|
0.00%
0/122
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/135
|
0.82%
1/122
|
|
Gastrointestinal disorders
Abdominal pain
|
0.74%
1/135
|
0.00%
0/122
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/135
|
0.82%
1/122
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/135
|
0.82%
1/122
|
|
General disorders
General physical health deterioration
|
0.74%
1/135
|
0.00%
0/122
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/135
|
0.82%
1/122
|
|
Infections and infestations
Pneumonia
|
0.00%
0/135
|
0.82%
1/122
|
|
Investigations
Weight decreased
|
0.00%
0/135
|
0.82%
1/122
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.2%
3/135
|
0.82%
1/122
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic
|
0.00%
0/135
|
0.82%
1/122
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/135
|
0.82%
1/122
|
|
Nervous system disorders
Myotonia
|
0.00%
0/135
|
0.82%
1/122
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/135
|
0.82%
1/122
|
Other adverse events
| Measure |
Inhaled Human Insulin (Exubera®)
n=135 participants at risk
Pre-prandial inhaled insulin regimen administered three times a day (TID) using Exubera® Inhaler device; insulin packaged as 1 or 3 milligram (mg) dry powder insulin. Initial daily dose determined based on subject's body weight and divided into 3 doses administered prior to major meals. Pre-meal doses modified based on meal size and pre-prandial blood glucose readings. Subjects combined 1 and 3 mg doses before each meal to control post-prandial glycemia in addition to continuing their usual oral (PO) drugs at the pre-study doses unless clinical need justified a dose modification.
|
Insulin Glargine (Lantus®)
n=122 participants at risk
Insulin glargine (Lantus®) 10 International Units (IU) injected subcutaneously (SC) once daily (QD) at the same time of day (morning dose recommended) for the duration of the study (26 Weeks) using a pen device where available. Daily dose of insulin glargine modified based on glucose measurements at the discretion of the treating physician. Insulin glargine added initially to subject's usual oral regimen and was to be continued at pre-study doses unless clinical need justified a dose modification.
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.74%
1/135
|
1.6%
2/122
|
|
Eye disorders
Vision blurred
|
1.5%
2/135
|
0.00%
0/122
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/135
|
1.6%
2/122
|
|
Gastrointestinal disorders
Diarrhoea
|
4.4%
6/135
|
3.3%
4/122
|
|
General disorders
Chest pain
|
1.5%
2/135
|
0.00%
0/122
|
|
General disorders
Fatigue
|
3.7%
5/135
|
3.3%
4/122
|
|
General disorders
Oedema
|
1.5%
2/135
|
0.82%
1/122
|
|
General disorders
Oedema peripheral
|
6.7%
9/135
|
1.6%
2/122
|
|
Infections and infestations
Bronchitis
|
1.5%
2/135
|
0.82%
1/122
|
|
Infections and infestations
Gastroenteritis
|
2.2%
3/135
|
0.00%
0/122
|
|
Infections and infestations
Influenza
|
2.2%
3/135
|
1.6%
2/122
|
|
Infections and infestations
Nasopharyngitis
|
13.3%
18/135
|
16.4%
20/122
|
|
Infections and infestations
Sinusitis
|
0.00%
0/135
|
1.6%
2/122
|
|
Infections and infestations
Upper respiratory tract infection
|
2.2%
3/135
|
2.5%
3/122
|
|
Infections and infestations
Urinary tract infection
|
0.74%
1/135
|
1.6%
2/122
|
|
Investigations
Weight increased
|
0.74%
1/135
|
1.6%
2/122
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
70.4%
95/135
|
53.3%
65/122
|
|
Metabolism and nutrition disorders
Increased appetite
|
1.5%
2/135
|
0.00%
0/122
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.4%
6/135
|
3.3%
4/122
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/135
|
1.6%
2/122
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.2%
3/135
|
0.82%
1/122
|
|
Nervous system disorders
Dizziness
|
0.74%
1/135
|
1.6%
2/122
|
|
Nervous system disorders
Headache
|
5.2%
7/135
|
2.5%
3/122
|
|
Nervous system disorders
Paraesthesia
|
2.2%
3/135
|
0.00%
0/122
|
|
Nervous system disorders
Sciatica
|
1.5%
2/135
|
0.82%
1/122
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
9/135
|
1.6%
2/122
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.4%
6/135
|
0.82%
1/122
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/135
|
1.6%
2/122
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.5%
2/135
|
0.82%
1/122
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/135
|
1.6%
2/122
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.5%
2/135
|
1.6%
2/122
|
|
Vascular disorders
Hypertension
|
4.4%
6/135
|
1.6%
2/122
|
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