A Clinical Trial Comparing the Efficacy and Safety of Exubera® and Lantus®

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00391027
• Collaborator: (none)
• Enrollment: 261
• Locations: 62
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To compare efficacy and safety of Exubera® vs Lantus® in patients with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Insulin Glargine (Lantus®); Drug: Inhaled Human Insulin (Exubera®)	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 261 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Six Month, Open-Label Outpatient, Randomized Parallel Group Trial Assessing The Impact Of Dry Powder Inhaled Insulin (Exubera®) On Glycemic Control Compared To Insulin Glargine (Lantus®) In Patients With Type 2 Diabetes Mellitus Who Are Poorly Controlled On A Combination Of Two Or More Oral Agents
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin Glargine (Lantus®)	Drug: Insulin Glargine (Lantus®); Patient will be randomized to Lantus® while remaining on pre-study oral hypoglycemic agents.
Active Comparator: Inhaled Human Insulin (Exubera®)	Drug: Inhaled Human Insulin (Exubera®); Patient will be randomized inhaled insulin while remaining on pre-study oral hypoglycemic agents.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 [Baseline, Week 26]

   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.

Secondary Outcome Measures

1. Change From Baseline in HbA1c Prior to Week 26 [Baseline, Week 2, Week 4, Week 8, Week 12, and Week 18]

   Change (measured as percent) from baseline calculated as HbA1c at observation minus HbA1c at baseline.

2. Number of Subjects With HbA1c < 6.5 % [Week 26]

   Number of subjects with glycemic control HbA1c measurement of < 6.5 % at observation.

3. Number of Subjects With HbA1c < 7.0 % [Week 26]

   Number of subjects with glycemic control HbA1c measurement of < 7.0 % at observation.

4. Number of Subjects With HbA1c < 8.0 % [Week 26]

   Number of subjects with glycemic control HbA1c measurement of < 8.0 % at observation.

5. Change From Baseline in Fasting Plasma Glucose (FPG) Level [Baseline, Week 26]

   FPG measured as milligrams/deciliter (mg/dl). Change from baseline calculated as FPG at observation minus FPG at baseline.

6. Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point) [Baseline, Week 26]

   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.

7. Number of Subjects With Hypoglycemic Events by Severity [Week 26]

   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.

8. Number of Events of Nocturnal Hypoglycemia [Week 26]

   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.

9. Change From Baseline in Body Weight [Baseline, Week 26]

   Change from baseline calculated as body weight at observation minus body weight at baseline.

10. Change From Baseline in Body Mass Index (BMI) [Baseline, Week 26]

    BMI measured as kilograms per meter squared (kg/m2). Change calculated as BMI at observation minus BMI at baseline.

11. Number of Subjects Discontinued Due to Insufficient Clinical Response [Week 26]

    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.

12. Change From Baseline in Treatment Satisfaction, Quality of Life, and Mental Health [Week 26]

    Subject 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.

13. Continuous Glucose Monitoring System (CGMS) 24-hour Glucose Profile in a Subset of Patients [Baseline, Week 26]

    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.

14. Change From Baseline in Cardiovascular (CV) Biomarkers - High Sensitive C-reactive Protein (Hs-CRP) [Baseline, Week 26]

    Change from baseline in CV biomarker hs-CRP (milligrams per deciliter [mg/dl]) calculated as hs-CRP at observation minus hs-CRP at baseline.

15. Change From Baseline in CV Biomarkers - Interleukin 6 (IL-6) [Baseline, Week 26]

    Change from baseline in IL-6 (picograms per milliliter [pg/ml]) calculated as IL-6 at observation minus IL-6 at baseline.

16. Change From Baseline in CV Biomarkers - Thrombin-antithrombin Complexes (Tat-complexes) [Baseline, Week 26]

    Change from baseline in tat-complexes (nanograms per milliliter [ng/ml]) calculated as tat-complexes at observation minus tat-complexes at baseline.

17. Change From Baseline in CV Biomarkers - Soluble Tissue Factor (STF) [Baseline, Week 26]

    Change from baseline in soluble tissue factor (pg/ml) calculated as STF at observation minus STF at baseline.

18. Change From Baseline in Urinary Free 8-iso Prostaglandin F2-alpha (α) in a Subset of Subjects [Baseline, Week 26]

    Urinary 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diabetes Mellitus, Type 2 on oral agents

• Age > 30 years

Exclusion Criteria:

• Severe Asthma, severe Chronic Obstructive Pulmonary Disease

• Smoking

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bornem		Belgium	2800
2	Pfizer Investigational Site	Brussels		Belgium	1070
3	Pfizer Investigational Site	Genk		Belgium	3600
4	Pfizer Investigational Site	Liège 1		Belgium	4000
5	Pfizer Investigational Site	Kuopio		Finland	70210
6	Pfizer Investigational Site	Lahti		Finland	15110
7	Pfizer Investigational Site	Oulu		Finland	90100
8	Pfizer Investigational Site	Besancon		France	25030
9	Pfizer Investigational Site	Corbeil Essonnes Cedex		France	91106
10	Pfizer Investigational Site	LA Rochelle CEDEX		France	17019
11	Pfizer Investigational Site	Marseille Cedex 5		France	13385
12	Pfizer Investigational Site	Paris Cedex 10		France	75475
13	Pfizer Investigational Site	Valenciennes Cedex 1		France	59300
14	Pfizer Investigational Site	Altenburg		Germany	04600
15	Pfizer Investigational Site	Eisenach		Germany	99817
16	Pfizer Investigational Site	Hamburg		Germany	20253
17	Pfizer Investigational Site	Hohenmoelsen		Germany	06679
18	Pfizer Investigational Site	Leipzig		Germany	04103
19	Pfizer Investigational Site	Neuss		Germany	41460
20	Pfizer Investigational Site	Riesa		Germany	01587
21	Pfizer Investigational Site	Wangen / Allgaeu		Germany	88239
22	Pfizer Investigational Site	Den Bosch		Netherlands	5233 VG
23	Pfizer Investigational Site	Den Haag		Netherlands	2512 VA
24	Pfizer Investigational Site	Eindhoven		Netherlands	5631 BM
25	Pfizer Investigational Site	Nijmegen		Netherlands	6525 EC
26	Pfizer Investigational Site	Venlo		Netherlands	5912 BL
27	Pfizer Investigational Site	Honefoss	Buskerud	Norway	3505
28	Pfizer Investigational Site	Bergen		Norway	5012
29	Pfizer Investigational Site	Jessheim		Norway	2050
30	Pfizer Investigational Site	Lysaker		Norway
31	Pfizer Investigational Site	Skedsmokorset		Norway	N-2020
32	Pfizer Investigational Site	Lask		Poland	98-100
33	Pfizer Investigational Site	Lodz		Poland	90-030
34	Pfizer Investigational Site	Lodz		Poland	93-338
35	Pfizer Investigational Site	Lublin		Poland	20-536
36	Pfizer Investigational Site	Warszawa		Poland	02-097
37	Pfizer Investigational Site	Palma de Mallorca	Islas Baleares	Spain	07014
38	Pfizer Investigational Site	Inca	Mallorca	Spain	07300
39	Pfizer Investigational Site	La Laguna	Santa Cruz de Tenerife	Spain	38320
40	Pfizer Investigational Site	Alzira	Valencia	Spain	46600
41	Pfizer Investigational Site	A Coruña		Spain	15006
42	Pfizer Investigational Site	Huelva		Spain	21080
43	Pfizer Investigational Site	Malaga		Spain	29006
44	Pfizer Investigational Site	Valencia		Spain	46015
45	Pfizer Investigational Site	Boras		Sweden	501 82
46	Pfizer Investigational Site	Eksjo		Sweden	575 36
47	Pfizer Investigational Site	Goteborg		Sweden	412 55
48	Pfizer Investigational Site	Goteborg		Sweden	41665
49	Pfizer Investigational Site	Harnosand		Sweden	871 82
50	Pfizer Investigational Site	Helsingborg		Sweden	25220
51	Pfizer Investigational Site	Järfälla		Sweden	177 31
52	Pfizer Investigational Site	Kristianstad		Sweden	291 54
53	Pfizer Investigational Site	Linkoping		Sweden	581 85
54	Pfizer Investigational Site	Lulea		Sweden	972 33
55	Pfizer Investigational Site	Malmo		Sweden	211 52
56	Pfizer Investigational Site	Motala		Sweden	591 85
57	Pfizer Investigational Site	Stockholm		Sweden	118 83
58	Pfizer Investigational Site	Uddevalla		Sweden	451 50
59	Pfizer Investigational Site	Umea		Sweden	901 85
60	Pfizer Investigational Site	Vaxjo		Sweden	351 85
61	Pfizer Investigational Site	Bruderholz		Switzerland	4101
62	Pfizer Investigational Site	St. Gallen		Switzerland	CH-9007

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00391027
• Other Study ID Numbers: A2171084
• First Posted: Oct 23, 2006
• Last Update Posted: Jul 23, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Pfizer: type 2 diabetes, insulin, glycemic control
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine

Study Results

Participant Flow

Pre-assignment Detail	Number of subjects randomized = 261; number of subjects treated (out of 261 randomized) = 257.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Period Title: Overall Study
STARTED	135	122
COMPLETED	110	110
NOT COMPLETED	25	12

Baseline Characteristics

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)	Total
Arm/Group Description	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®) 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 of all reporting groups
Overall Participants	135	122	257
Age, Customized (participants) [Number]
18 - 44 years	8 5.9%	3 2.5%	11 4.3%
45 - 64 years	78 57.8%	71 58.2%	149 58%
> = 65 years	49 36.3%	48 39.3%	97 37.7%
Sex: Female, Male (Count of Participants)
Female	54 40%	51 41.8%	105 40.9%
Male	81 60%	71 58.2%	152 59.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
Description	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.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Mean (Standard Deviation) [percent]	-1.7 (1.19)	-1.4 (1.14)

2. Secondary Outcome

Title	Change From Baseline in HbA1c Prior to Week 26
Description	Change (measured as percent) from baseline calculated as HbA1c at observation minus HbA1c at baseline.
Time Frame	Baseline, Week 2, Week 4, Week 8, Week 12, and Week 18

Outcome Measure Data

Analysis Population Description

FAS; LOCF; (n) = number of subjects with analyzable data at observation for inhaled insulin and insulin glargine, respectively.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Week 2 (n = 128, 108)	-0.4 (0.40)	-0.3 (0.40)
Week 4 (n = 134, 121)	-0.8 (0.61)	-0.6 (0.58)
Week 8 (n = 134, 121)	-1.3 (0.86)	-1.1 (0.85)
Week 12 (n = 134, 121)	-1.6 (1.08)	-1.3 (0.99)
Week 18 (n = 134, 121)	-1.7 (1.16)	-1.5 (1.11)

3. Secondary Outcome

Title	Number of Subjects With HbA1c < 6.5 %
Description	Number of subjects with glycemic control HbA1c measurement of < 6.5 % at observation.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Number [participants]	37 27.4%	23 18.9%

4. Secondary Outcome

Title	Number of Subjects With HbA1c < 7.0 %
Description	Number of subjects with glycemic control HbA1c measurement of < 7.0 % at observation.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Number [participants]	84 62.2%	67 54.9%

5. Secondary Outcome

Title	Number of Subjects With HbA1c < 8.0 %
Description	Number of subjects with glycemic control HbA1c measurement of < 8.0 % at observation.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Number [participants]	121 89.6%	108 88.5%

6. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) Level
Description	FPG measured as milligrams/deciliter (mg/dl). Change from baseline calculated as FPG at observation minus FPG at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	120
Mean (Standard Deviation) [mg/dl]	-30.6 (49.04)	-60.1 (51.95)

7. Secondary Outcome

Title	Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point)
Description	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.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF; (n) = number of subjects with analyzable data at observation for inhaled insulin and insulin glargine, respectively.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Average overall absolute BG (n=101, 95)	-45.0 (46.26)	-43.7 (48.41)
Average pre-meal BG (n=101, 95)	-38.1 (43.24)	-50.7 (47.54)
Average post-meal BG (n=99, 91)	-64.5 (59.35)	-49.6 (58.33)
Change from pre-meal to post-meal BG (n=99, 91)	-24.5 (35.28)	1.6 (39.82)

8. Secondary Outcome

Title	Number of Subjects With Hypoglycemic Events by Severity
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Week 26 Mild, Moderate	26 19.3%	32 26.2%
Week 26 Severe	1 0.7%	1 0.8%

9. Secondary Outcome

Title	Number of Events of Nocturnal Hypoglycemia
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Number [events]	159	81

10. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Change from baseline calculated as body weight at observation minus body weight at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	125	118
Mean (Standard Deviation) [kilograms (kg)]	2.2 (3.57)	1.1 (3.43)

11. Secondary Outcome

Title	Change From Baseline in Body Mass Index (BMI)
Description	BMI measured as kilograms per meter squared (kg/m2). Change calculated as BMI at observation minus BMI at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	125	118
Mean (Standard Deviation) [kg/m2]	0.7 (1.24)	0.4 (1.20)

12. Secondary Outcome

Title	Number of Subjects Discontinued Due to Insufficient Clinical Response
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Safety population: all subjects who received at least 1 dose of study medication.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	135	122
Number [participants]	3 2.2%	0 0%

13. Secondary Outcome

Title	Change From Baseline in Treatment Satisfaction, Quality of Life, and Mental Health
Description	Subject 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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Continuous Glucose Monitoring System (CGMS) 24-hour Glucose Profile in a Subset of Patients
Description	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.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	134	121
Week 26: 24-hour mean (n=14, 12)	107.6 (18.46)	102.1 (18.02)
Week 26: 24-hour SD (n=14, 12)	33.7 (17.22)	30.7 (8.09)

15. Secondary Outcome

Title	Change From Baseline in Cardiovascular (CV) Biomarkers - High Sensitive C-reactive Protein (Hs-CRP)
Description	Change from baseline in CV biomarker hs-CRP (milligrams per deciliter [mg/dl]) calculated as hs-CRP at observation minus hs-CRP at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	106	98
Mean (Standard Deviation) [mg/dl]	0.2 (1.92)	-0.1 (1.56)

16. Secondary Outcome

Title	Change From Baseline in CV Biomarkers - Interleukin 6 (IL-6)
Description	Change from baseline in IL-6 (picograms per milliliter [pg/ml]) calculated as IL-6 at observation minus IL-6 at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	55	61
Mean (Standard Deviation) [pg/ml]	-1.1 (4.05)	-2.4 (10.41)

17. Secondary Outcome

Title	Change From Baseline in CV Biomarkers - Thrombin-antithrombin Complexes (Tat-complexes)
Description	Change from baseline in tat-complexes (nanograms per milliliter [ng/ml]) calculated as tat-complexes at observation minus tat-complexes at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	31	18
Mean (Standard Deviation) [ng/ml]	-3.4 (10.00)	-40.4 (166.90)

18. Secondary Outcome

Title	Change From Baseline in CV Biomarkers - Soluble Tissue Factor (STF)
Description	Change from baseline in soluble tissue factor (pg/ml) calculated as STF at observation minus STF at baseline.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

FAS; LOCF.

Arm/Group Title	Inhaled Human Insulin (Exubera®)	Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
Measure Participants	2	5
Mean (Standard Deviation) [pg/ml]	230.2 (279.92)	170.4 (174.07)

19. Secondary Outcome

Title	Change From Baseline in Urinary Free 8-iso Prostaglandin F2-alpha (α) in a Subset of Subjects
Description	Urinary 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.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Inhaled Human Insulin (Exubera®)		Insulin Glargine (Lantus®)
Arm/Group Description	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®) 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.
All Cause Mortality
	Inhaled Human Insulin (Exubera®)		Insulin Glargine (Lantus®)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Inhaled Human Insulin (Exubera®)		Insulin Glargine (Lantus®)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/135 (5.9%)		10/122 (8.2%)
Blood and lymphatic system disorders
Anaemia	0/135 (0%)		2/122 (1.6%)
Cardiac disorders
Arrhythmia supraventricular	1/135 (0.7%)		0/122 (0%)
Atrial fibrillation	0/135 (0%)		2/122 (1.6%)
Coronary artery disease	0/135 (0%)		1/122 (0.8%)
Left ventricular dysfunction	1/135 (0.7%)		0/122 (0%)
Myocardial infarction	0/135 (0%)		1/122 (0.8%)
Myocardial ischaemia	1/135 (0.7%)		0/122 (0%)
Ear and labyrinth disorders
Vertigo	0/135 (0%)		1/122 (0.8%)
Gastrointestinal disorders
Abdominal pain	1/135 (0.7%)		0/122 (0%)
Gastric ulcer	0/135 (0%)		1/122 (0.8%)
Gastric ulcer haemorrhage	0/135 (0%)		1/122 (0.8%)
General disorders
General physical health deterioration	1/135 (0.7%)		0/122 (0%)
Hepatobiliary disorders
Jaundice	0/135 (0%)		1/122 (0.8%)
Infections and infestations
Pneumonia	0/135 (0%)		1/122 (0.8%)
Investigations
Weight decreased	0/135 (0%)		1/122 (0.8%)
Metabolism and nutrition disorders
Hypoglycaemia	3/135 (2.2%)		1/122 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	0/135 (0%)		1/122 (0.8%)
Nervous system disorders
Diabetic neuropathy	0/135 (0%)		1/122 (0.8%)
Myotonia	0/135 (0%)		1/122 (0.8%)
Renal and urinary disorders
Urinary retention	0/135 (0%)		1/122 (0.8%)
Other (Not Including Serious) Adverse Events
	Inhaled Human Insulin (Exubera®)		Insulin Glargine (Lantus®)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/135 (77.8%)		81/122 (66.4%)
Cardiac disorders
Angina pectoris	1/135 (0.7%)		2/122 (1.6%)
Eye disorders
Vision blurred	2/135 (1.5%)		0/122 (0%)
Gastrointestinal disorders
Abdominal pain	0/135 (0%)		2/122 (1.6%)
Diarrhoea	6/135 (4.4%)		4/122 (3.3%)
General disorders
Chest pain	2/135 (1.5%)		0/122 (0%)
Fatigue	5/135 (3.7%)		4/122 (3.3%)
Oedema	2/135 (1.5%)		1/122 (0.8%)
Oedema peripheral	9/135 (6.7%)		2/122 (1.6%)
Infections and infestations
Bronchitis	2/135 (1.5%)		1/122 (0.8%)
Gastroenteritis	3/135 (2.2%)		0/122 (0%)
Influenza	3/135 (2.2%)		2/122 (1.6%)
Nasopharyngitis	18/135 (13.3%)		20/122 (16.4%)
Sinusitis	0/135 (0%)		2/122 (1.6%)
Upper respiratory tract infection	3/135 (2.2%)		3/122 (2.5%)
Urinary tract infection	1/135 (0.7%)		2/122 (1.6%)
Investigations
Weight increased	1/135 (0.7%)		2/122 (1.6%)
Metabolism and nutrition disorders
Hypoglycaemia	95/135 (70.4%)		65/122 (53.3%)
Increased appetite	2/135 (1.5%)		0/122 (0%)
Musculoskeletal and connective tissue disorders
Back pain	6/135 (4.4%)		4/122 (3.3%)
Musculoskeletal pain	0/135 (0%)		2/122 (1.6%)
Pain in extremity	3/135 (2.2%)		1/122 (0.8%)
Nervous system disorders
Dizziness	1/135 (0.7%)		2/122 (1.6%)
Headache	7/135 (5.2%)		3/122 (2.5%)
Paraesthesia	3/135 (2.2%)		0/122 (0%)
Sciatica	2/135 (1.5%)		1/122 (0.8%)
Respiratory, thoracic and mediastinal disorders
Cough	9/135 (6.7%)		2/122 (1.6%)
Dyspnoea	6/135 (4.4%)		1/122 (0.8%)
Skin and subcutaneous tissue disorders
Eczema	0/135 (0%)		2/122 (1.6%)
Hyperhidrosis	2/135 (1.5%)		1/122 (0.8%)
Pruritus	0/135 (0%)		2/122 (1.6%)
Rash	2/135 (1.5%)		2/122 (1.6%)
Vascular disorders
Hypertension	6/135 (4.4%)		2/122 (1.6%)

Limitations/Caveats

Enrollment period concluded earlier than planned due to cancellation of Exubera® program by sponsor; enrollment was undersized to meet requirements of its inferential objectives. Revised analysis approach was descriptive with no inferential analyses.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.