VOLUME: Exubera Large Simple Trial To Evaluate Long-Term Pulmonary And Cardiovascular Safety

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00359801
• Collaborator: (none)
• Enrollment: 1,976
• Locations: 197
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 10
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term pulmonary and cardiovascular safety of Exubera in routine clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care	Phase 4

Detailed Description

Pfizer announced in October 2007 that it would stop marketing Exubera. At that time, Pfizer committed to continued marketing until it returned the licensing rights for the technology to Nektar. Following the announcement, enrollment was halted. Subjects already enrolled and receiving treatment at the time of the halt in enrollment could continue in the study in accordance with the protocol. Nektar, the company from which Pfizer licensed Exubera, announced on April 9, 2008 that it had stopped its search for a new marketing partner. Accordingly, there will be no commercial availability of Exubera. As a result, an amendment was filed on April 16, 2008 specifying that all subjects randomized to Exubera had to be transitioned to usual diabetes care, and all study subjects followed for serious adverse events for 6 months. In accordance with this amendment, study A2171069 was terminated on April 29, 2009. Neither safety nor efficacy reasons were the cause of the study termination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1976 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An International, Multicenter, Large Simple Trial To Evaluate The Long-Term Pulmonary And Cardiovascular Safety Of Exubera In Patients With Diabetes Mellitus
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exubera	Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Subjects are randomized to use Exubera. Following initial use of randomized treatment, physicians and subjects are free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice). Enrolling physicians are provided with the approved local label for Exubera to guide prescribing and treatment decisions.
Active Comparator: Usual Diabetes Care	Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care; Subjects are randomized to use usual diabetes care. Following initial use of randomized treatment, physicians and subjects are free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice).; Other Names: Non-Exubera

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline [Baseline, Month 6, Year 1, Year 2, Index Visit]

   Persistent decline in FEV1 exceeding 20% from baseline: observed decline in FEV1 exceeding 20% from baseline, 3 months after a confirmed decline (2 consecutive declines within 1 month) in FEV1 exceeding 20% from baseline. Second pulmonary function test (PFT) that confirmed decline was to occur within 14-42 days of the decline. Persistence: PFT that established persistence was to occur within 60-120 days of the confirming (2nd) decline. Index Visit: date subject had final Scheduled spirometry; was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.

2. Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects [Baseline, Month 6, Year 1, Year 2, Index Visit]

   Confirmed FEV1 decline: any two consecutive declines that are >= 14 days apart. The pulmonary function test that established persistence occured >= 60 days after the initial decline. A confirmed decline: any two consecutive declines ≥ 14 days apart. The third PFT that established persistence was to occur ≥ 60 days after the initial decline. Index Visit: date the subject had his/her final scheduled spirometry was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.

3. Time to Persistent Decline in FEV1 Exceeding 20% From Baseline [Baseline to 5 years]

   Elapsed time, in days, from the start of subject's participation in the study to the first reading of FEV1 that is: 20% or more below the subject's latest pre-study measurement, subsequently confirmed as a >20% decline [(baseline observed value minus visit observed value)/by baseline observed value *100], and assessed as persistent as defined by protocol process. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to latest valid FEV1 measurement for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.

Secondary Outcome Measures

1. Change From Baseline in Forced Expiratory Volume in One Second (FEV1) [Baseline, Week 26, Week 52, Week 104, Index Visit]

   Change from Baseline: mean of value of observed forced expiratory volume in the first second of forced exhalation [FEV1] in liters [L] at observation minus Baseline value. Index Visit: date subject had final scheduled spirometry; was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.

2. Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis [Baseline through End of Study]

   Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria. Definite: definite pneumonia, definite COPD, or definite asthma; possible: possible pneumonia, possible COPD, possible asthma, probable obstructive lung disease not otherwise specified or probable acute bronchitis; definite or possible: either definite or possible; insufficient: insufficient data.

3. Time to Event for Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis [Baseline to 5 years]

   Elapsed time, in days, from the start of a subject's participation in the study to the date of the first report of an event subsequently confirmed (according to protocol definition) as meeting the criteria for pulmonary SAE composite. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.

4. All-cause Mortality: Number of Deaths [Baseline through End of Study]

   Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria (confirmation of deaths by blinded adjudicator(s) through medical records or death certificates). Patients meeting the endpoint All Cause Mortality after adjudication by the endpoint committee.

5. Time to Event: All-cause Mortality [Baseline to 5 years]

   Time to all-cause mortality: elapsed time, in days, from the start of a subject's participation in the study to the date of the event subsequently confirmed (according to protocol definition) as meeting the criteria for all-cause mortality. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.

6. Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke [Baseline through End of Study]

   Endpoint committee adjudicated based on review of medical/hospital records; results classified using standard criteria. Definite: definite MI or stroke; Possible: possible MI or stroke; Other (non-MI, non-stroke): other cardiovascular event (non-MI, non-stroke); Definite or possible: either definite or possible or both; Insufficient: insufficient data; Death from cardiovascular or cerebrovascular: cardiovascular or cerebrovascular event; Definite or possible or death from cardiovascular or cerebrovascular: either definite or possible or both or cardiovascular or cerebrovascular event.

7. Time to Event for Cardiovascular Serious Adverse Event (SAE) Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction, or Non-fatal Stroke [Baseline to 5 years]

   Elapsed time, in days, from the start of a subject's participation in the study to the date of the first event subsequently confirmed (according to protocol definition) as meeting the criteria for cardiovascular SAE composite. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.

8. Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm [Baseline through End of Study]

   Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria. Definite or possible: anaphylaxis, angioedema/urticaria, bronchospasm or possible allergic reaction not otherwise specified (NOS); Insufficient: insufficient data.

9. Time to Event for Allergic Response Serious Adverse Event (SAE) Composite, Including: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm [Baseline to 5 years]

   Elapsed time, in days, from the start of a subject's participation in the study to the date of the first event subsequently confirmed (according to protocol definition) as meeting the criteria for allergic response. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.

10. Change in Glycosylated Hemoglobin (HbA1c) From Baseline [Baseline, Month 6, Year 1, Year 2, Index Visit]

    Baseline HbA1c: the latest determination prior to beginning study participation. Change from Baseline: HbA1c at observation (falling within the time window associated with a given analysis set) minus the baseline value.

11. Change in Glycosylated Hemoglobin (HbA1c) From Baseline [Baseline to 5 years]

    Baseline HbA1c taken as the latest determination prior to beginning study participation. Change = on-study value (for measurements falling within the time window associated with a given analysis set) minus the baseline value. Linear model with terms for treatment, baseline HbA1c, time on study, and subject within treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Eligible for receiving Exubera treatment based on the approved local label

Exclusion Criteria:

• Pregnant or lactating

• Have a progressive fatal disease or a life expectancy that prohibits them from participating in a five-year research study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bay Minette	Alabama	United States	36507-4185
2	Pfizer Investigational Site	Fairhope	Alabama	United States	36532
3	Pfizer Investigational Site	Graysville	Alabama	United States	35073
4	Pfizer Investigational Site	Pell City	Alabama	United States	35125
5	Pfizer Investigational Site	Phoenix	Arizona	United States	85016
6	Pfizer Investigational Site	Phoenix	Arizona	United States	85028
7	Pfizer Investigational Site	Phoenix	Arizona	United States	85029
8	Pfizer Investigational Site	Forrest City	Arkansas	United States	72335
9	Pfizer Investigational Site	Searcy	Arkansas	United States	72143
10	Pfizer Investigational Site	Cudahy	California	United States	90201
11	Pfizer Investigational Site	El Cajon	California	United States	92019
12	Pfizer Investigational Site	Huntington Beach	California	United States	92648
13	Pfizer Investigational Site	Rolling Hills Estates	California	United States	90274
14	Pfizer Investigational Site	San Jose	California	United States	95116
15	Pfizer Investigational Site	Santa Ana	California	United States	92704
16	Pfizer Investigational Site	Westminster	California	United States	92683
17	Pfizer Investigational Site	Denver	Colorado	United States	80219
18	Pfizer Investigational Site	Milford	Connecticut	United States	06460
19	Pfizer Investigational Site	Wilmington	Delaware	United States	19806
20	Pfizer Investigational Site	Boca Raton	Florida	United States	33433
21	Pfizer Investigational Site	Clearwater	Florida	United States	33756
22	Pfizer Investigational Site	Debary	Florida	United States	32713
23	Pfizer Investigational Site	Gainesville	Florida	United States	32605
24	Pfizer Investigational Site	Green Cove Springs	Florida	United States	32043
25	Pfizer Investigational Site	Hollywood	Florida	United States	33021
26	Pfizer Investigational Site	Kissimmee	Florida	United States	34741
27	Pfizer Investigational Site	Kissimmee	Florida	United States	34743
28	Pfizer Investigational Site	Marianna	Florida	United States	32446
29	Pfizer Investigational Site	Merritt Island	Florida	United States	32952
30	Pfizer Investigational Site	Miami	Florida	United States	33144
31	Pfizer Investigational Site	Niceville	Florida	United States	32578
32	Pfizer Investigational Site	Opa Locka	Florida	United States	33054-3818
33	Pfizer Investigational Site	Orange City	Florida	United States	32763
34	Pfizer Investigational Site	Ormond Beach	Florida	United States	32174
35	Pfizer Investigational Site	Pembroke Pines	Florida	United States	33027
36	Pfizer Investigational Site	Plantation	Florida	United States	33324
37	Pfizer Investigational Site	Port Charlotte	Florida	United States	33952
38	Pfizer Investigational Site	Tampa	Florida	United States	33607
39	Pfizer Investigational Site	Tampa	Florida	United States	33624
40	Pfizer Investigational Site	Atlanta	Georgia	United States	30318-2513
41	Pfizer Investigational Site	Atlanta	Georgia	United States	30342
42	Pfizer Investigational Site	Conyers	Georgia	United States	30013
43	Pfizer Investigational Site	Decatur	Georgia	United States	30035
44	Pfizer Investigational Site	Warner Robins	Georgia	United States	31088
45	Pfizer Investigational Site	Boise	Idaho	United States	83704
46	Pfizer Investigational Site	Greenville	Illinois	United States	62246
47	Pfizer Investigational Site	Libertyville	Illinois	United States	60048
48	Pfizer Investigational Site	Fishers	Indiana	United States	46038
49	Pfizer Investigational Site	Indianapolis	Indiana	United States	46229
50	Pfizer Investigational Site	Indianapolis	Indiana	United States	46254-5472
51	Pfizer Investigational Site	Des Moines	Iowa	United States	50315
52	Pfizer Investigational Site	Louisville	Kentucky	United States	40258
53	Pfizer Investigational Site	Mount Sterling	Kentucky	United States	40353
54	Pfizer Investigational Site	Bossier City	Louisiana	United States	71111
55	Pfizer Investigational Site	Auburn	Maine	United States	04210
56	Pfizer Investigational Site	Baltimore	Maryland	United States	21204
57	Pfizer Investigational Site	Elkton	Maryland	United States	21921
58	Pfizer Investigational Site	Glen Burnie	Maryland	United States	21061
59	Pfizer Investigational Site	Wheaton	Maryland	United States	20902
60	Pfizer Investigational Site	Boston	Massachusetts	United States	02110
61	Pfizer Investigational Site	Plymouth	Massachusetts	United States	02360
62	Pfizer Investigational Site	Ann Arbor	Michigan	United States	48104
63	Pfizer Investigational Site	Battle Creek	Michigan	United States	49014
64	Pfizer Investigational Site	Battle Creek	Michigan	United States	49017
65	Pfizer Investigational Site	Clinton	Michigan	United States	49236
66	Pfizer Investigational Site	Flint	Michigan	United States	48504
67	Pfizer Investigational Site	Muskegon	Michigan	United States	49444
68	Pfizer Investigational Site	Sterling Heights	Michigan	United States	48310
69	Pfizer Investigational Site	Troy	Michigan	United States	48084
70	Pfizer Investigational Site	Warren	Michigan	United States	48091
71	Pfizer Investigational Site	Saint Cloud	Minnesota	United States	56301
72	Pfizer Investigational Site	Grand Island	Nebraska	United States	68803
73	Pfizer Investigational Site	Incline Village	Nevada	United States	89452
74	Pfizer Investigational Site	Belleville	New Jersey	United States	07109
75	Pfizer Investigational Site	Belvidere	New Jersey	United States	07823
76	Pfizer Investigational Site	Glendora	New Jersey	United States	08029
77	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87106
78	Pfizer Investigational Site	Babylon	New York	United States	11702
79	Pfizer Investigational Site	Brooklyn	New York	United States	11224
80	Pfizer Investigational Site	New Hartford	New York	United States	13413
81	Pfizer Investigational Site	Rochester	New York	United States	14622
82	Pfizer Investigational Site	Williamsville	New York	United States	14221
83	Pfizer Investigational Site	Asheboro	North Carolina	United States	27203
84	Pfizer Investigational Site	Charlotte	North Carolina	United States	28227
85	Pfizer Investigational Site	Morehead City	North Carolina	United States	28557-3126
86	Pfizer Investigational Site	Raleigh	North Carolina	United States	27609
87	Pfizer Investigational Site	Raleigh	North Carolina	United States	27610
88	Pfizer Investigational Site	Shelby	North Carolina	United States	28150
89	Pfizer Investigational Site	Tabor City	North Carolina	United States	28463
90	Pfizer Investigational Site	Winston-Salem	North Carolina	United States	27103
91	Pfizer Investigational Site	Bismarck	North Dakota	United States	58501
92	Pfizer Investigational Site	Ashtabula	Ohio	United States	44004
93	Pfizer Investigational Site	Canton	Ohio	United States	44708
94	Pfizer Investigational Site	Cleveland	Ohio	United States	44113
95	Pfizer Investigational Site	Columbus	Ohio	United States	43207
96	Pfizer Investigational Site	Dayton	Ohio	United States	45419
97	Pfizer Investigational Site	McConnelsville	Ohio	United States	43756
98	Pfizer Investigational Site	Zanesville	Ohio	United States	43701
99	Pfizer Investigational Site	Clinton	Oklahoma	United States	73601
100	Pfizer Investigational Site	Bend	Oregon	United States	97701
101	Pfizer Investigational Site	Broomall	Pennsylvania	United States	19008
102	Pfizer Investigational Site	Dauphin	Pennsylvania	United States	17018
103	Pfizer Investigational Site	Fogelsville	Pennsylvania	United States	18051
104	Pfizer Investigational Site	Hanover	Pennsylvania	United States	17331
105	Pfizer Investigational Site	Harrisburg	Pennsylvania	United States	17112
106	Pfizer Investigational Site	Jeannette	Pennsylvania	United States	15644
107	Pfizer Investigational Site	Jenkintown	Pennsylvania	United States	19046
108	Pfizer Investigational Site	Jersey Shore	Pennsylvania	United States	17740
109	Pfizer Investigational Site	Norristown	Pennsylvania	United States	19401
110	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19153-2326
111	Pfizer Investigational Site	Plymouth Meeting	Pennsylvania	United States	19462
112	Pfizer Investigational Site	Tipton	Pennsylvania	United States	16684
113	Pfizer Investigational Site	Charleston	South Carolina	United States	29412
114	Pfizer Investigational Site	Florence	South Carolina	United States	29501
115	Pfizer Investigational Site	Greer	South Carolina	United States	29651
116	Pfizer Investigational Site	North Myrtle Beach	South Carolina	United States	29582
117	Pfizer Investigational Site	Germantown	Tennessee	United States	38138
118	Pfizer Investigational Site	Corpus Christi	Texas	United States	78414
119	Pfizer Investigational Site	Garland	Texas	United States	75041
120	Pfizer Investigational Site	Hurst	Texas	United States	76054
121	Pfizer Investigational Site	Kaufman	Texas	United States	75142
122	Pfizer Investigational Site	Lubbock	Texas	United States	79410
123	Pfizer Investigational Site	Midland	Texas	United States	79705
124	Pfizer Investigational Site	San Antonio	Texas	United States	78229
125	Pfizer Investigational Site	San Marcos	Texas	United States	78666
126	Pfizer Investigational Site	Stephenville	Texas	United States	76401
127	Pfizer Investigational Site	Webster	Texas	United States	77598
128	Pfizer Investigational Site	Layton	Utah	United States	84041
129	Pfizer Investigational Site	Chesapeake	Virginia	United States	23320
130	Pfizer Investigational Site	Ettrick	Virginia	United States	23803
131	Pfizer Investigational Site	Burnsville	West Virginia	United States	26335
132	Pfizer Investigational Site	Charleston	West Virginia	United States	25314
133	Pfizer Investigational Site	Aschaffenburg		Germany	63739
134	Pfizer Investigational Site	Bad Doberan		Germany	18209
135	Pfizer Investigational Site	Bad Groenenbach		Germany	87730
136	Pfizer Investigational Site	Bad Oeynhausen		Germany	32549
137	Pfizer Investigational Site	Bad Staffelstein		Germany	96231
138	Pfizer Investigational Site	Berlin		Germany	12247
139	Pfizer Investigational Site	Berlin		Germany	13355
140	Pfizer Investigational Site	Bonn		Germany	53179
141	Pfizer Investigational Site	Chemnitz		Germany	09130
142	Pfizer Investigational Site	Datteln		Germany	45711
143	Pfizer Investigational Site	Dortmund		Germany	44137
144	Pfizer Investigational Site	Dortmund		Germany	44339
145	Pfizer Investigational Site	Eisenach		Germany	99817
146	Pfizer Investigational Site	Emden		Germany	26725
147	Pfizer Investigational Site	Essen		Germany	45329
148	Pfizer Investigational Site	Esslingen		Germany	73728
149	Pfizer Investigational Site	Falkensee		Germany	14612
150	Pfizer Investigational Site	Friedberg		Germany	86316
151	Pfizer Investigational Site	Fulda		Germany	36037
152	Pfizer Investigational Site	Hagen		Germany	58091
153	Pfizer Investigational Site	Hamburg		Germany	21073
154	Pfizer Investigational Site	Hamburg		Germany	22041
155	Pfizer Investigational Site	Hohenmoelsen		Germany	06679
156	Pfizer Investigational Site	Jena		Germany	07743
157	Pfizer Investigational Site	Koeln		Germany	51069
158	Pfizer Investigational Site	Leverkusen		Germany	51371
159	Pfizer Investigational Site	Mahlberg		Germany	77972
160	Pfizer Investigational Site	Mannheim		Germany	68161
161	Pfizer Investigational Site	Markdorf		Germany	88677
162	Pfizer Investigational Site	Marl		Germany	45770
163	Pfizer Investigational Site	Meissen		Germany	01662
164	Pfizer Investigational Site	Muenster		Germany	48145
165	Pfizer Investigational Site	Muenster		Germany	48153
166	Pfizer Investigational Site	Neuwied		Germany	56564
167	Pfizer Investigational Site	Nuernberg		Germany	90480
168	Pfizer Investigational Site	Reinfeld		Germany	23858
169	Pfizer Investigational Site	Riesa		Germany	01587
170	Pfizer Investigational Site	Schluechtern		Germany	36381
171	Pfizer Investigational Site	Siegen		Germany	57072
172	Pfizer Investigational Site	Suhl		Germany	98529
173	Pfizer Investigational Site	Villingen-Schwenningen		Germany	78054
174	Pfizer Investigational Site	Wangen I. Allgaeu		Germany	88239
175	Pfizer Investigational Site	Wangen		Germany	88239
176	Pfizer Investigational Site	Warburg		Germany	34414
177	Pfizer Investigational Site	Manati		Puerto Rico	00674
178	Pfizer Investigational Site	Boras		Sweden	503 30
179	Pfizer Investigational Site	Forshaga		Sweden	667 32
180	Pfizer Investigational Site	Goteborg		Sweden	41345
181	Pfizer Investigational Site	Lilla Edet		Sweden	46330
182	Pfizer Investigational Site	Chesterfield	Derbyshire	United Kingdom	S40 4TF
183	Pfizer Investigational Site	Ashford	Middlesex	United Kingdom	TW15 3EA
184	Pfizer Investigational Site	Dronfield	Sheffield	United Kingdom	S18 1RU
185	Pfizer Investigational Site	Weybridge	Surrey	United Kingdom	KT15 2BH
186	Pfizer Investigational Site	Woking	Surrey	United Kingdom	GU22 7EY
187	Pfizer Investigational Site	Rugby	Warwickshire	United Kingdom	CV22 5PX
188	Pfizer Investigational Site	Warminster	Wiltshire	United Kingdom	BA12 9AA
189	Pfizer Investigational Site	Sheffield	Yorkshire	United Kingdom	S7 2DW
190	Pfizer Investigational Site	Airdrie		United Kingdom	ML6 0JS
191	Pfizer Investigational Site	Bath		United Kingdom	BA2 3HT
192	Pfizer Investigational Site	Bath		United Kingdom	BA2 4BY
193	Pfizer Investigational Site	Birmingham		United Kingdom	B37 7TR
194	Pfizer Investigational Site	Leicester		United Kingdom	LE1 5WW
195	Pfizer Investigational Site	Newcastle Upon Tyne		United Kingdom	NE15 6TQ
196	Pfizer Investigational Site	Newcastle Upon Tyne		United Kingdom	NE3 3QJ
197	Pfizer Investigational Site	Westbury		United Kingdom	BA13 3JD

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.

• ClinicalTrials.gov Identifier: NCT00359801
• Other Study ID Numbers: A2171069
• First Posted: Aug 2, 2006
• Last Update Posted: Feb 2, 2010
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Large Simple Trial
• Additional relevant MeSH terms: Diabetes Mellitus; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from primary care centers, diabetes and endocrinology clinics, and academic centers, and participated in the study between 22 July 2006 and 29 April 2009.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Period Title: Overall Study
STARTED	987	989
COMPLETED	682	769
NOT COMPLETED	305	220

Baseline Characteristics

Arm/Group Title	Exubera®	Non-Exubera®	Total
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care	Total of all reporting groups
Overall Participants	987	989	1976
Age, Customized (participants) [Number]
18-44 years	114 11.6%	133 13.4%	247 12.5%
45-64 years	576 58.4%	552 55.8%	1128 57.1%
65-74 years	242 24.5%	245 24.8%	487 24.6%
75-84 years	52 5.3%	57 5.8%	109 5.5%
>= 85 years	3 0.3%	2 0.2%	5 0.3%
Sex: Female, Male (Count of Participants)
Female	439 44.5%	434 43.9%	873 44.2%
Male	548 55.5%	555 56.1%	1103 55.8%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline
Description	Persistent decline in FEV1 exceeding 20% from baseline: observed decline in FEV1 exceeding 20% from baseline, 3 months after a confirmed decline (2 consecutive declines within 1 month) in FEV1 exceeding 20% from baseline. Second pulmonary function test (PFT) that confirmed decline was to occur within 14-42 days of the decline. Persistence: PFT that established persistence was to occur within 60-120 days of the confirming (2nd) decline. Index Visit: date subject had final Scheduled spirometry; was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.
Time Frame	Baseline, Month 6, Year 1, Year 2, Index Visit

Outcome Measure Data

Analysis Population Description

Full Analysis Set: all randomized subjects.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Initial FEV1 Decline	100 10.1%	112 11.3%
Initial FEV1 Decline but not a Confirmed Decline	81 8.2%	105 10.6%
Confirmed FEV1 Decline	19 1.9%	7 0.7%
Confirmed FEV1 Decline but not Persistent Decline	11 1.1%	7 0.7%
Persistent FEV1 Decline	8 0.8%	0 0%

2. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Description	Change from Baseline: mean of value of observed forced expiratory volume in the first second of forced exhalation [FEV1] in liters [L] at observation minus Baseline value. Index Visit: date subject had final scheduled spirometry; was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.
Time Frame	Baseline, Week 26, Week 52, Week 104, Index Visit

Outcome Measure Data

Analysis Population Description

FAS; (n) = number of subjects with analyzable data at observation for Exubera® and Non-Exubera®, respectively.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Baseline (n=985, 987)	2.661 (0.838)	2.684 (0.888)
Week 26 (n=813, 852)	-0.009 (0.568)	-0.035 (0.509)
Week 52 (n=470, 482)	-0.032 (0.411)	-0.056 (0.465)
Week 104 (n=3, 1)	-0.103 (0.607)	-1.270 (0.000)
Index Visit (n=729, 803)	-0.000 (0.559)	-0.018 (0.580)

3. Secondary Outcome

Title	Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis
Description	Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria. Definite: definite pneumonia, definite COPD, or definite asthma; possible: possible pneumonia, possible COPD, possible asthma, probable obstructive lung disease not otherwise specified or probable acute bronchitis; definite or possible: either definite or possible; insufficient: insufficient data.
Time Frame	Baseline through End of Study

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Definite	4	1
Possible	3	2
Definite or Possible	7	3
Insufficient	4	2

4. Secondary Outcome

Title	Time to Event for Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis
Description	Elapsed time, in days, from the start of a subject's participation in the study to the date of the first report of an event subsequently confirmed (according to protocol definition) as meeting the criteria for pulmonary SAE composite. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.
Time Frame	Baseline to 5 years

Outcome Measure Data

Analysis Population Description

FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	0	0

5. Secondary Outcome

Title	All-cause Mortality: Number of Deaths
Description	Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria (confirmation of deaths by blinded adjudicator(s) through medical records or death certificates). Patients meeting the endpoint All Cause Mortality after adjudication by the endpoint committee.
Time Frame	Baseline through End of Study

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Number [participants]	12 1.2%	9 0.9%

6. Secondary Outcome

Title	Time to Event: All-cause Mortality
Description	Time to all-cause mortality: elapsed time, in days, from the start of a subject's participation in the study to the date of the event subsequently confirmed (according to protocol definition) as meeting the criteria for all-cause mortality. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.
Time Frame	Baseline to 5 years

Outcome Measure Data

Analysis Population Description

FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	0	0

7. Primary Outcome

Title	Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects
Description	Confirmed FEV1 decline: any two consecutive declines that are >= 14 days apart. The pulmonary function test that established persistence occured >= 60 days after the initial decline. A confirmed decline: any two consecutive declines ≥ 14 days apart. The third PFT that established persistence was to occur ≥ 60 days after the initial decline. Index Visit: date the subject had his/her final scheduled spirometry was to occur within 2 months of Institutional Review Board/Ethics approval of April 2008 amendment.
Time Frame	Baseline, Month 6, Year 1, Year 2, Index Visit

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Initial FEV1 Decline	100 10.1%	112 11.3%
Initial FEV1 Decline but not a Confirmed Decline	62 6.3%	74 7.5%
Confirmed FEV1 Decline	38 3.9%	38 3.8%
Confirmed FEV1 Decline but not Persistent Decline	11 1.1%	14 1.4%
Persistent FEV1 Decline	27 2.7%	24 2.4%

8. Secondary Outcome

Title	Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke
Description	Endpoint committee adjudicated based on review of medical/hospital records; results classified using standard criteria. Definite: definite MI or stroke; Possible: possible MI or stroke; Other (non-MI, non-stroke): other cardiovascular event (non-MI, non-stroke); Definite or possible: either definite or possible or both; Insufficient: insufficient data; Death from cardiovascular or cerebrovascular: cardiovascular or cerebrovascular event; Definite or possible or death from cardiovascular or cerebrovascular: either definite or possible or both or cardiovascular or cerebrovascular event.
Time Frame	Baseline through End of Study

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Definite	5	3
Possible	5	6
Other (non-myocardial infarction, non-stroke)	15	9
Definite or Possible	10	9
Insufficient	9	7
Death from Cardiovascular or Cerebrovascular	2	4
Definite or Possible, or Death from Cardiovascular	12	11

9. Secondary Outcome

Title	Time to Event for Cardiovascular Serious Adverse Event (SAE) Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction, or Non-fatal Stroke
Description	Elapsed time, in days, from the start of a subject's participation in the study to the date of the first event subsequently confirmed (according to protocol definition) as meeting the criteria for cardiovascular SAE composite. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.
Time Frame	Baseline to 5 years

Outcome Measure Data

Analysis Population Description

FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	0	0

10. Secondary Outcome

Title	Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm
Description	Endpoint committee adjudicated the endpoint based on review of medical and hospital records, and results were classified using standard criteria. Definite or possible: anaphylaxis, angioedema/urticaria, bronchospasm or possible allergic reaction not otherwise specified (NOS); Insufficient: insufficient data.
Time Frame	Baseline through End of Study

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Definite or Possible	2	0
Insufficient	3	0

11. Secondary Outcome

Title	Time to Event for Allergic Response Serious Adverse Event (SAE) Composite, Including: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm
Description	Elapsed time, in days, from the start of a subject's participation in the study to the date of the first event subsequently confirmed (according to protocol definition) as meeting the criteria for allergic response. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to the latest contact with the subject for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.
Time Frame	Baseline to 5 years

Outcome Measure Data

Analysis Population Description

FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	0	0

12. Secondary Outcome

Title	Change in Glycosylated Hemoglobin (HbA1c) From Baseline
Description	Baseline HbA1c: the latest determination prior to beginning study participation. Change from Baseline: HbA1c at observation (falling within the time window associated with a given analysis set) minus the baseline value.
Time Frame	Baseline, Month 6, Year 1, Year 2, Index Visit

Outcome Measure Data

Analysis Population Description

FAS; (n) = number of subjects with analyzable data at observation for Exubera® and Non-Exubera®, respectively.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	987	989
Baseline (n=978, 985)	8.6 (1.9)	8.5 (1.9)
Week 26: Observed Value (804, 849)	8.0 (1.8)	8.0 (1.8)
Week 26: Change from Baseline (n=800, 848)	-0.5 (1.7)	-0.5 (1.6)
Week 52: Observed Value (n=468, 489)	7.8 (1.7)	7.7 (1.6)
Week 52: Change from Baseline (n=467, 489)	-0.4 (1.6)	-0.6 (1.6)
Week 104: Observed Value (n=3, 1)	6.6 (1.2)	6.0 (0)
Week 104: Change from Baseline (n=3, 1)	-1.0 (1.6)	-2.7 (0)
Index Visit: Observed Value (n=673, 754)	8.1 (3.0)	8.0 (3.5)
Index Visit: Change from Baseline (n=669, 754)	-0.3 (2.9)	-0.5 (3.3)

13. Secondary Outcome

Title	Change in Glycosylated Hemoglobin (HbA1c) From Baseline
Description	Baseline HbA1c taken as the latest determination prior to beginning study participation. Change = on-study value (for measurements falling within the time window associated with a given analysis set) minus the baseline value. Linear model with terms for treatment, baseline HbA1c, time on study, and subject within treatment.
Time Frame	Baseline to 5 years

Outcome Measure Data

Analysis Population Description

FAS. Due to early study termination, the originally planned inferential analysis (linear model) for change from baseline was not done.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	0	0

14. Primary Outcome

Title	Time to Persistent Decline in FEV1 Exceeding 20% From Baseline
Description	Elapsed time, in days, from the start of subject's participation in the study to the first reading of FEV1 that is: 20% or more below the subject's latest pre-study measurement, subsequently confirmed as a >20% decline [(baseline observed value minus visit observed value)/by baseline observed value *100], and assessed as persistent as defined by protocol process. Censoring time: elapsed time, in days, from the start of a subject's participation in the study to latest valid FEV1 measurement for the particular analysis set of interest. Cox proportional hazards model to estimate treatment effect.
Time Frame	Baseline to 5 years

Outcome Measure Data

Analysis Population Description

FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.

Arm/Group Title	Exubera®	Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care	Usual diabetes care
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Two additional subjects experienced SAEs that were not listed under a treatment group due to data error: Injury, Poisoning and Procedural Complications system organ class (1 subject; drug exposure during preganancy), and Musculoskeletal and Connective System Disorders System Organ Class (1 subject; neuropathic arthropathy).
Arm/Group Title	Exubera®		Non-Exubera®
Arm/Group Description	Exubera® plus usual diabetes care		Usual diabetes care
All Cause Mortality
	Exubera®		Non-Exubera®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exubera®		Non-Exubera®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/987 (12.6%)		109/989 (11%)
Blood and lymphatic system disorders
Anaemia	2/987 (0.2%)		0/989 (0%)
Iron deficiency anaemia	1/987 (0.1%)		1/989 (0.1%)
Lymphatic obstruction	0/987 (0%)		1/989 (0.1%)
Cardiac disorders
Acute coronary syndrome	1/987 (0.1%)		0/989 (0%)
Angina pectoris	2/987 (0.2%)		3/989 (0.3%)
Angina unstable	0/987 (0%)		2/989 (0.2%)
Aortic valve incompetence	1/987 (0.1%)		0/989 (0%)
Arrhythmia	2/987 (0.2%)		1/989 (0.1%)
Arteriosclerosis coronary artery	1/987 (0.1%)		0/989 (0%)
Atrial fibrillation	2/987 (0.2%)		1/989 (0.1%)
Atrial flutter	1/987 (0.1%)		0/989 (0%)
Atrial tachycardia	1/987 (0.1%)		0/989 (0%)
Cardiac arrest	0/987 (0%)		1/989 (0.1%)
Cardiac failure	0/987 (0%)		1/989 (0.1%)
Cardiac failure congestive	3/987 (0.3%)		1/989 (0.1%)
Cardio-respiratory arrest	1/987 (0.1%)		0/989 (0%)
Cardiomyopathy	0/987 (0%)		1/989 (0.1%)
Congestive cardiomyopathy	1/987 (0.1%)		0/989 (0%)
Coronary artery disease	5/987 (0.5%)		2/989 (0.2%)
Coronary artery occlusion	0/987 (0%)		2/989 (0.2%)
Coronary artery stenosis	2/987 (0.2%)		1/989 (0.1%)
Hypertensive heart disease	1/987 (0.1%)		0/989 (0%)
Ischaemic cardiomyopathy	1/987 (0.1%)		0/989 (0%)
Myocardial infarction	5/987 (0.5%)		4/989 (0.4%)
Myocardial ischaemia	1/987 (0.1%)		0/989 (0%)
Paroxysmal arrhythmia	1/987 (0.1%)		0/989 (0%)
Tricuspid valve incompetence	1/987 (0.1%)		0/989 (0%)
Ventricular tachycardia	1/987 (0.1%)		1/989 (0.1%)
Congenital, familial and genetic disorders
Cerebral palsy	1/987 (0.1%)		0/989 (0%)
Endocrine disorders
Goitre	1/987 (0.1%)		0/989 (0%)
Eye disorders
Blindness	0/987 (0%)		1/989 (0.1%)
Cataract	1/987 (0.1%)		1/989 (0.1%)
Diabetic retinopathy	1/987 (0.1%)		0/989 (0%)
Eye degenerative disorder	0/987 (0%)		1/989 (0.1%)
Macular oedema	0/987 (0%)		1/989 (0.1%)
Gastrointestinal disorders
Abdominal hernia	0/987 (0%)		1/989 (0.1%)
Abdominal pain	0/987 (0%)		1/989 (0.1%)
Colitis ulcerative	0/987 (0%)		1/989 (0.1%)
Duodenitis	1/987 (0.1%)		0/989 (0%)
Gastric haemorrhage	1/987 (0.1%)		0/989 (0%)
Gastritis	0/987 (0%)		2/989 (0.2%)
Gastrointestinal haemorrhage	2/987 (0.2%)		1/989 (0.1%)
Inguinal hernia	2/987 (0.2%)		1/989 (0.1%)
Pancreatitis	0/987 (0%)		1/989 (0.1%)
Pancreatitis acute	0/987 (0%)		1/989 (0.1%)
Pancreatitis chronic	1/987 (0.1%)		0/989 (0%)
Small intestinal obstruction	1/987 (0.1%)		0/989 (0%)
Volvulus	0/987 (0%)		1/989 (0.1%)
General disorders
Cardiac death	0/987 (0%)		1/989 (0.1%)
Chest discomfort	1/987 (0.1%)		1/989 (0.1%)
Chest pain	7/987 (0.7%)		9/989 (0.9%)
Death	2/987 (0.2%)		1/989 (0.1%)
Discomfort	1/987 (0.1%)		0/989 (0%)
Drug ineffective	2/987 (0.2%)		0/989 (0%)
Inflammation	1/987 (0.1%)		0/989 (0%)
Malaise	1/987 (0.1%)		0/989 (0%)
Oedema peripheral	1/987 (0.1%)		0/989 (0%)
Organ failure	0/987 (0%)		1/989 (0.1%)
Sudden death	1/987 (0.1%)		1/989 (0.1%)
Hepatobiliary disorders
Biliary colic	1/987 (0.1%)		0/989 (0%)
Cholecystitis acute	0/987 (0%)		1/989 (0.1%)
Cholelithiasis	0/987 (0%)		2/989 (0.2%)
Immune system disorders
Drug hypersensitivity	1/987 (0.1%)		0/989 (0%)
Infections and infestations
Abscess	0/987 (0%)		1/989 (0.1%)
Abscess neck	1/987 (0.1%)		0/989 (0%)
Appendicitis	0/987 (0%)		1/989 (0.1%)
Cellulitis	2/987 (0.2%)		2/989 (0.2%)
Diverticulitis	1/987 (0.1%)		0/989 (0%)
Empyema	0/987 (0%)		1/989 (0.1%)
Erysipelas	1/987 (0.1%)		0/989 (0%)
Gangrene	0/987 (0%)		1/989 (0.1%)
Gastroenteritis	0/987 (0%)		1/989 (0.1%)
Gastrointestinal infection	1/987 (0.1%)		0/989 (0%)
Herpes zoster	0/987 (0%)		1/989 (0.1%)
Infected skin ulcer	0/987 (0%)		1/989 (0.1%)
Lobar pneumonia	1/987 (0.1%)		0/989 (0%)
Lower respiratory tract infection	0/987 (0%)		1/989 (0.1%)
Lymph node tuberculosis	1/987 (0.1%)		0/989 (0%)
Pneumonia	3/987 (0.3%)		2/989 (0.2%)
Pyelonephritis	0/987 (0%)		1/989 (0.1%)
Scrotal abscess	1/987 (0.1%)		0/989 (0%)
Sepsis	1/987 (0.1%)		1/989 (0.1%)
Staphylococcal infection	1/987 (0.1%)		0/989 (0%)
Subcutaneous abscess	1/987 (0.1%)		1/989 (0.1%)
Tooth abscess	0/987 (0%)		1/989 (0.1%)
Urinary tract infection	0/987 (0%)		1/989 (0.1%)
Injury, poisoning and procedural complications
Accident	0/987 (0%)		1/989 (0.1%)
Acetabulum fracture	1/987 (0.1%)		0/989 (0%)
Ankle fracture	2/987 (0.2%)		2/989 (0.2%)
Compression fracture	0/987 (0%)		1/989 (0.1%)
Device malfunction	1/987 (0.1%)		0/989 (0%)
Device occlusion	1/987 (0.1%)		0/989 (0%)
Drug exposure during pregnancy	1/987 (0.1%)		0/989 (0%)
Fall	3/987 (0.3%)		2/989 (0.2%)
Head injury	1/987 (0.1%)		1/989 (0.1%)
Hip fracture	0/987 (0%)		1/989 (0.1%)
Implantable defibrillator malfunction	0/987 (0%)		1/989 (0.1%)
Lower limb fracture	0/987 (0%)		1/989 (0.1%)
Meniscus lesion	1/987 (0.1%)		0/989 (0%)
Multiple injuries	1/987 (0.1%)		0/989 (0%)
Paternal drugs affecting foetus	0/987 (0%)		1/989 (0.1%)
Post procedural haematoma	1/987 (0.1%)		0/989 (0%)
Rib fracture	1/987 (0.1%)		1/989 (0.1%)
Scapula fracture	0/987 (0%)		1/989 (0.1%)
Subdural haematoma	1/987 (0.1%)		2/989 (0.2%)
Tendon rupture	2/987 (0.2%)		0/989 (0%)
Therapeutic agent toxicity	1/987 (0.1%)		0/989 (0%)
Wound	1/987 (0.1%)		0/989 (0%)
Investigations
Anti-insulin antibody increased	1/987 (0.1%)		0/989 (0%)
Blood glucose decreased	1/987 (0.1%)		0/989 (0%)
Blood glucose increased	3/987 (0.3%)		0/989 (0%)
Catheterisation cardiac	0/987 (0%)		1/989 (0.1%)
Forced expiratory volume decreased	1/987 (0.1%)		0/989 (0%)
Metabolism and nutrition disorders
Dehydration	0/987 (0%)		1/989 (0.1%)
Diabetes mellitus	1/987 (0.1%)		0/989 (0%)
Diabetes mellitus inadequate control	2/987 (0.2%)		1/989 (0.1%)
Diabetic complication	0/987 (0%)		1/989 (0.1%)
Diabetic foot	1/987 (0.1%)		0/989 (0%)
Diabetic ketoacidosis	1/987 (0.1%)		5/989 (0.5%)
Hypercalcaemia	0/987 (0%)		1/989 (0.1%)
Hyperglycaemia	2/987 (0.2%)		2/989 (0.2%)
Hyperkalaemia	0/987 (0%)		1/989 (0.1%)
Hypoglycaemia	7/987 (0.7%)		6/989 (0.6%)
Ketoacidosis	1/987 (0.1%)		0/989 (0%)
Obesity	1/987 (0.1%)		0/989 (0%)
Type 1 diabetes mellitus	0/987 (0%)		1/989 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/987 (0.1%)		0/989 (0%)
Arthropathy	0/987 (0%)		1/989 (0.1%)
Back pain	1/987 (0.1%)		0/989 (0%)
Intervertebral disc disorder	0/987 (0%)		1/989 (0.1%)
Intervertebral disc protrusion	4/987 (0.4%)		0/989 (0%)
Monarthritis	1/987 (0.1%)		0/989 (0%)
Neuropathic arthropathy	2/987 (0.2%)		0/989 (0%)
Osteoarthritis	2/987 (0.2%)		2/989 (0.2%)
Osteonecrosis	1/987 (0.1%)		0/989 (0%)
Rotator cuff syndrome	0/987 (0%)		2/989 (0.2%)
Spinal column stenosis	1/987 (0.1%)		0/989 (0%)
Spinal disorder	1/987 (0.1%)		0/989 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/987 (0.1%)		0/989 (0%)
Adenocarcinoma pancreas	0/987 (0%)		1/989 (0.1%)
B-cell lymphoma	1/987 (0.1%)		0/989 (0%)
Basal cell carcinoma	0/987 (0%)		1/989 (0.1%)
Breast cancer	1/987 (0.1%)		0/989 (0%)
Colon cancer	1/987 (0.1%)		0/989 (0%)
Gammopathy	1/987 (0.1%)		0/989 (0%)
Glioblastoma	1/987 (0.1%)		0/989 (0%)
Hepatic neoplasm malignant	1/987 (0.1%)		1/989 (0.1%)
Leukaemia	0/987 (0%)		1/989 (0.1%)
Lipoma	0/987 (0%)		1/989 (0.1%)
Lung neoplasm malignant	3/987 (0.3%)		0/989 (0%)
Lymphoma	1/987 (0.1%)		0/989 (0%)
Metastases to liver	1/987 (0.1%)		0/989 (0%)
Metastatic neoplasm	1/987 (0.1%)		0/989 (0%)
Non-Hodgkin's lymphoma	1/987 (0.1%)		0/989 (0%)
Pancreatic carcinoma	1/987 (0.1%)		1/989 (0.1%)
Prostate cancer	0/987 (0%)		1/989 (0.1%)
Renal cell carcinoma	0/987 (0%)		1/989 (0.1%)
Renal neoplasm	0/987 (0%)		1/989 (0.1%)
Squamous cell carcinoma	1/987 (0.1%)		1/989 (0.1%)
Uterine leiomyoma	0/987 (0%)		2/989 (0.2%)
Nervous system disorders
Brain stem infarction	1/987 (0.1%)		0/989 (0%)
Carotid artery stenosis	1/987 (0.1%)		1/989 (0.1%)
Central nervous system lesion	1/987 (0.1%)		0/989 (0%)
Cerebral infarction	1/987 (0.1%)		0/989 (0%)
Cerebrovascular accident	6/987 (0.6%)		3/989 (0.3%)
Convulsion	0/987 (0%)		4/989 (0.4%)
Facial paresis	1/987 (0.1%)		0/989 (0%)
Haemorrhage intracranial	0/987 (0%)		1/989 (0.1%)
Paraesthesia	2/987 (0.2%)		0/989 (0%)
Presyncope	0/987 (0%)		1/989 (0.1%)
Sciatica	0/987 (0%)		1/989 (0.1%)
Syncope	2/987 (0.2%)		4/989 (0.4%)
Thalamic infarction	0/987 (0%)		1/989 (0.1%)
Transient ischaemic attack	2/987 (0.2%)		1/989 (0.1%)
Psychiatric disorders
Depression	1/987 (0.1%)		0/989 (0%)
Drug abuse	1/987 (0.1%)		0/989 (0%)
Emotional disorder	0/987 (0%)		1/989 (0.1%)
Intentional self-injury	1/987 (0.1%)		0/989 (0%)
Mental status changes	1/987 (0.1%)		0/989 (0%)
Suicide attempt	1/987 (0.1%)		0/989 (0%)
Renal and urinary disorders
Calculus ureteric	1/987 (0.1%)		0/989 (0%)
Hydroureter	0/987 (0%)		1/989 (0.1%)
Nephrolithiasis	1/987 (0.1%)		1/989 (0.1%)
Renal failure	1/987 (0.1%)		2/989 (0.2%)
Renal failure chronic	2/987 (0.2%)		0/989 (0%)
Tubulointerstitial nephritis	1/987 (0.1%)		0/989 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/987 (0%)		1/989 (0.1%)
Chronic obstructive pulmonary disease	1/987 (0.1%)		0/989 (0%)
Dyspnoea	5/987 (0.5%)		1/989 (0.1%)
Dyspnoea exertional	1/987 (0.1%)		0/989 (0%)
Lung disorder	0/987 (0%)		1/989 (0.1%)
Lung infiltration	1/987 (0.1%)		0/989 (0%)
Pulmonary embolism	0/987 (0%)		2/989 (0.2%)
Pulmonary mass	1/987 (0.1%)		0/989 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/987 (0.1%)		0/989 (0%)
Blister	0/987 (0%)		1/989 (0.1%)
Decubitus ulcer	0/987 (0%)		1/989 (0.1%)
Dermal cyst	1/987 (0.1%)		0/989 (0%)
Diabetic ulcer	1/987 (0.1%)		0/989 (0%)
Pruritus	1/987 (0.1%)		0/989 (0%)
Surgical and medical procedures
Cardiac operation	1/987 (0.1%)		0/989 (0%)
Coronary arterial stent insertion	0/987 (0%)		1/989 (0.1%)
Coronary artery bypass	0/987 (0%)		1/989 (0.1%)
Toe amputation	1/987 (0.1%)		0/989 (0%)
Vascular disorders
Accelerated hypertension	0/987 (0%)		1/989 (0.1%)
Aortic stenosis	1/987 (0.1%)		0/989 (0%)
Arterial occlusive disease	1/987 (0.1%)		1/989 (0.1%)
Deep vein thrombosis	0/987 (0%)		1/989 (0.1%)
Haematoma	1/987 (0.1%)		0/989 (0%)
Hypertension	1/987 (0.1%)		0/989 (0%)
Hypertensive crisis	0/987 (0%)		1/989 (0.1%)
Hypotension	0/987 (0%)		1/989 (0.1%)
Orthostatic hypotension	0/987 (0%)		1/989 (0.1%)
Peripheral arterial occlusive disease	1/987 (0.1%)		0/989 (0%)
Peripheral artery aneurysm	0/987 (0%)		1/989 (0.1%)
Other (Not Including Serious) Adverse Events
	Exubera®		Non-Exubera®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/987 (2.6%)		11/989 (1.1%)
Cardiac disorders
Angina pectoris	1/987 (0.1%)		0/989 (0%)
Eye disorders
Vision blurred	1/987 (0.1%)		0/989 (0%)
Gastrointestinal disorders
Gingival pain	1/987 (0.1%)		0/989 (0%)
Nausea	0/987 (0%)		1/989 (0.1%)
General disorders
Adverse drug reaction	1/987 (0.1%)		0/989 (0%)
Fatigue	1/987 (0.1%)		1/989 (0.1%)
Influenza like illness	1/987 (0.1%)		0/989 (0%)
Oedema peripheral	1/987 (0.1%)		0/989 (0%)
Infections and infestations
Bronchitis	1/987 (0.1%)		0/989 (0%)
Cellulitis	0/987 (0%)		1/989 (0.1%)
Gingival infection	1/987 (0.1%)		0/989 (0%)
Herpes zoster	1/987 (0.1%)		0/989 (0%)
Lobar pneumonia	1/987 (0.1%)		0/989 (0%)
Nasopharyngitis	0/987 (0%)		1/989 (0.1%)
Sinusitis	1/987 (0.1%)		0/989 (0%)
Skin bacterial infection	1/987 (0.1%)		0/989 (0%)
Staphylococcal infection	1/987 (0.1%)		0/989 (0%)
Upper respiratory tract infection	1/987 (0.1%)		0/989 (0%)
Viral pharyngitis	1/987 (0.1%)		0/989 (0%)
Injury, poisoning and procedural complications
Tooth fracture	1/987 (0.1%)		0/989 (0%)
Investigations
Blood glucose increased	3/987 (0.3%)		0/989 (0%)
Cardiac murmur	1/987 (0.1%)		0/989 (0%)
Catheterisation cardiac	0/987 (0%)		1/989 (0.1%)
Forced expiratory volume decreased	0/987 (0%)		2/989 (0.2%)
Weight decreased	1/987 (0.1%)		0/989 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/987 (0.1%)		1/989 (0.1%)
Hypoglycaemia	2/987 (0.2%)		1/989 (0.1%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/987 (0.1%)		0/989 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	0/987 (0%)		1/989 (0.1%)
Nervous system disorders
Facial palsy	1/987 (0.1%)		0/989 (0%)
Haemorrhage intracranial	0/987 (0%)		1/989 (0.1%)
Headache	1/987 (0.1%)		0/989 (0%)
Psychiatric disorders
Insomnia	1/987 (0.1%)		0/989 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/987 (0%)		1/989 (0.1%)
Cough	6/987 (0.6%)		0/989 (0%)
Dry throat	1/987 (0.1%)		0/989 (0%)
Dyspnoea	3/987 (0.3%)		0/989 (0%)
Oropharyngeal pain	1/987 (0.1%)		0/989 (0%)
Painful respiration	1/987 (0.1%)		0/989 (0%)
Pulmonary congestion	1/987 (0.1%)		0/989 (0%)
Wheezing	1/987 (0.1%)		0/989 (0%)
Skin and subcutaneous tissue disorders
Stasis dermatitis	0/987 (0%)		1/989 (0.1%)
Surgical and medical procedures
Stent placement	1/987 (0.1%)		0/989 (0%)
Vascular disorders
Temporal arteritis	1/987 (0.1%)		0/989 (0%)
Vascular stenosis	1/987 (0.1%)		0/989 (0%)

Limitations/Caveats

Pursuant to Pfizer's announcement that it would exit marketing of Exubera®, study enrollment was halted on 26-October-2007.

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.