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

NCT00359801 | Completed Phase 4 Results DMC

• 1 other identifier: A2171069
• Study Type: interventional
• Target: 1,976
• Locations: 5 countries
• Sites: 197

Brief Summary

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

Conditions

Diabetes Mellitus

Keywords

Large Simple Trial

Outcome Measures

Primary Outcomes (3)

• Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline

  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.

  Baseline, Month 6, Year 1, Year 2, Index Visit

• Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects

  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.

  Baseline, Month 6, Year 1, Year 2, Index Visit

• Time to Persistent Decline in FEV1 Exceeding 20% From Baseline

  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.

  Baseline to 5 years

Secondary Outcomes (11)

• Change From Baseline in Forced Expiratory Volume in One Second (FEV1)

  Baseline, Week 26, Week 52, Week 104, Index Visit

• Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis

  Baseline through End of Study

• 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

• All-cause Mortality: Number of Deaths

  Baseline through End of Study

• Time to Event: All-cause Mortality

  Baseline to 5 years

Study Arms (2)

Exubera

EXPERIMENTAL

Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care

Usual Diabetes Care

ACTIVE COMPARATOR

Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care

Interventions

Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care DRUG

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.

Exubera

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (197)

Pfizer Investigational Site

Bay Minette, Alabama, 36507-4185, United States

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Fairhope, Alabama, 36532, United States

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Graysville, Alabama, 35073, United States

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Pell City, Alabama, 35125, United States

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Phoenix, Arizona, 85016, United States

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Phoenix, Arizona, 85028, United States

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Phoenix, Arizona, 85029, United States

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Forrest City, Arkansas, 72335, United States

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Searcy, Arkansas, 72143, United States

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Cudahy, California, 90201, United States

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El Cajon, California, 92019, United States

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Huntington Beach, California, 92648, United States

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Rolling Hills Estates, California, 90274, United States

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San Jose, California, 95116, United States

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Santa Ana, California, 92704, United States

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Westminster, California, 92683, United States

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Denver, Colorado, 80219, United States

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Milford, Connecticut, 06460, United States

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Wilmington, Delaware, 19806, United States

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Boca Raton, Florida, 33433, United States

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Clearwater, Florida, 33756, United States

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DeBary, Florida, 32713, United States

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Gainesville, Florida, 32605, United States

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Green Cove Springs, Florida, 32043, United States

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Hollywood, Florida, 33021, United States

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Kissimmee, Florida, 34741, United States

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Kissimmee, Florida, 34743, United States

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Marianna, Florida, 32446, United States

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Merritt Island, Florida, 32952, United States

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Miami, Florida, 33144, United States

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Niceville, Florida, 32578, United States

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Opa-locka, Florida, 33054-3818, United States

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Orange City, Florida, 32763, United States

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Ormond Beach, Florida, 32174, United States

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Pembroke Pines, Florida, 33027, United States

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Plantation, Florida, 33324, United States

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Port Charlotte, Florida, 33952, United States

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Tampa, Florida, 33607, United States

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Tampa, Florida, 33624, United States

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Atlanta, Georgia, 30318-2513, United States

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Atlanta, Georgia, 30342, United States

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Conyers, Georgia, 30013, United States

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Decatur, Georgia, 30035, United States

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Warner Robins, Georgia, 31088, United States

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Boise, Idaho, 83704, United States

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Greenville, Illinois, 62246, United States

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Libertyville, Illinois, 60048, United States

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Fishers, Indiana, 46038, United States

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Indianapolis, Indiana, 46229, United States

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Indianapolis, Indiana, 46254-5472, United States

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Des Moines, Iowa, 50315, United States

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Louisville, Kentucky, 40258, United States

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Mount Sterling, Kentucky, 40353, United States

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Bossier City, Louisiana, 71111, United States

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Auburn, Maine, 04210, United States

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Baltimore, Maryland, 21204, United States

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Elkton, Maryland, 21921, United States

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Glen Burnie, Maryland, 21061, United States

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Wheaton, Maryland, 20902, United States

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Boston, Massachusetts, 02110, United States

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Plymouth, Massachusetts, 02360, United States

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Ann Arbor, Michigan, 48104, United States

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Battle Creek, Michigan, 49014, United States

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Battle Creek, Michigan, 49017, United States

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Clinton, Michigan, 49236, United States

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Flint, Michigan, 48504, United States

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Muskegon, Michigan, 49444, United States

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Sterling Heights, Michigan, 48310, United States

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Troy, Michigan, 48084, United States

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Warren, Michigan, 48091, United States

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Saint Cloud, Minnesota, 56301, United States

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Grand Island, Nebraska, 68803, United States

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Incline Village, Nevada, 89452, United States

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Belleville, New Jersey, 07109, United States

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Belvidere, New Jersey, 07823, United States

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Glendora, New Jersey, 08029, United States

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Albuquerque, New Mexico, 87106, United States

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Babylon, New York, 11702, United States

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Brooklyn, New York, 11224, United States

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New Hartford, New York, 13413, United States

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Rochester, New York, 14622, United States

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Williamsville, New York, 14221, United States

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Asheboro, North Carolina, 27203, United States

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Charlotte, North Carolina, 28227, United States

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Morehead City, North Carolina, 28557-3126, United States

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Raleigh, North Carolina, 27609, United States

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Raleigh, North Carolina, 27610, United States

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Shelby, North Carolina, 28150, United States

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Tabor City, North Carolina, 28463, United States

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Winston-Salem, North Carolina, 27103, United States

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Bismarck, North Dakota, 58501, United States

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Ashtabula, Ohio, 44004, United States

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Canton, Ohio, 44708, United States

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Cleveland, Ohio, 44113, United States

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Columbus, Ohio, 43207, United States

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Dayton, Ohio, 45419, United States

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McConnelsville, Ohio, 43756, United States

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Zanesville, Ohio, 43701, United States

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Clinton, Oklahoma, 73601, United States

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Bend, Oregon, 97701, United States

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Broomall, Pennsylvania, 19008, United States

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Dauphin, Pennsylvania, 17018, United States

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Fogelsville, Pennsylvania, 18051, United States

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Hanover, Pennsylvania, 17331, United States

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Harrisburg, Pennsylvania, 17112, United States

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Jeannette, Pennsylvania, 15644, United States

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Jenkintown, Pennsylvania, 19046, United States

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Jersey Shore, Pennsylvania, 17740, United States

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Norristown, Pennsylvania, 19401, United States

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Philadelphia, Pennsylvania, 19153-2326, United States

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Plymouth Meeting, Pennsylvania, 19462, United States

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Tipton, Pennsylvania, 16684, United States

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Charleston, South Carolina, 29412, United States

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Florence, South Carolina, 29501, United States

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Greer, South Carolina, 29651, United States

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North Myrtle Beach, South Carolina, 29582, United States

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Germantown, Tennessee, 38138, United States

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Corpus Christi, Texas, 78414, United States

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Garland, Texas, 75041, United States

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Hurst, Texas, 76054, United States

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Kaufman, Texas, 75142, United States

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Lubbock, Texas, 79410, United States

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Midland, Texas, 79705, United States

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San Antonio, Texas, 78229, United States

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San Marcos, Texas, 78666, United States

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Stephenville, Texas, 76401, United States

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Webster, Texas, 77598, United States

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Layton, Utah, 84041, United States

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Chesapeake, Virginia, 23320, United States

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Ettrick, Virginia, 23803, United States

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Burnsville, West Virginia, 26335, United States

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Charleston, West Virginia, 25314, United States

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Aschaffenburg, 63739, Germany

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Bad Doberan, 18209, Germany

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Bad Grönenbach, 87730, Germany

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Bad Oeynhausen, 32549, Germany

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Bad Staffelstein, 96231, Germany

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Berlin, 12247, Germany

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Berlin, 13355, Germany

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Bonn, 53179, Germany

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Chemnitz, 09130, Germany

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Cologne, 51069, Germany

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Datteln, 45711, Germany

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Dortmund, 44137, Germany

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Dortmund, 44339, Germany

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Eisenach, 99817, Germany

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Emden, 26725, Germany

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Essen, 45329, Germany

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Esslingen am Neckar, 73728, Germany

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Falkensee, 14612, Germany

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Friedberg, 86316, Germany

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Fulda, 36037, Germany

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Hagen, 58091, Germany

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Hamburg, 21073, Germany

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Hamburg, 22041, Germany

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Hohenmölsen, 06679, Germany

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Jena, 07743, Germany

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Leverkusen, 51371, Germany

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Mahlberg, 77972, Germany

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Mannheim, 68161, Germany

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Markdorf, 88677, Germany

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Marl, 45770, Germany

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Meissen, 01662, Germany

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Münster, 48145, Germany

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Münster, 48153, Germany

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Neuwied, 56564, Germany

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Nuremberg, 90480, Germany

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Reinfeld, 23858, Germany

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Riesa, 01587, Germany

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Schlüchtern, 36381, Germany

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Siegen, 57072, Germany

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Suhl, 98529, Germany

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Villingen-Schwenningen, 78054, Germany

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Wangen, 88239, Germany

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Wangen I. Allgaeu, 88239, Germany

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Warburg, 34414, Germany

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Manatí, 00674, Puerto Rico

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Borås, 503 30, Sweden

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Forshaga, 667 32, Sweden

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Gothenburg, 41345, Sweden

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Lilla Edet, 46330, Sweden

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Chesterfield, Derbyshire, S40 4TF, United Kingdom

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Ashford, Middlesex, TW15 3EA, United Kingdom

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Dronfield, Sheffield, S18 1RU, United Kingdom

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Weybridge, SURREY, KT15 2BH, United Kingdom

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Woking, Surrey, GU22 7EY, United Kingdom

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Rugby, Warwickshire, CV22 5PX, United Kingdom

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Warminster, WILTSHIRE, BA12 9AA, United Kingdom

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Sheffield, Yorkshire, S7 2DW, United Kingdom

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Airdrie, ML6 0JS, United Kingdom

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Bath, BA2 3HT, United Kingdom

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Bath, BA2 4BY, United Kingdom

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Birmingham, B37 7TR, United Kingdom

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Leicester, LE1 5WW, United Kingdom

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Newcastle upon Tyne, NE15 6TQ, United Kingdom

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Newcastle upon Tyne, NE3 3QJ, United Kingdom

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Westbury, BA13 3JD, United Kingdom

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Related Publications (2)

• Gatto NM, Bracken MB, Kolitsopoulos F, Duggan WT, Koch GG, Wise RA, Jackson NC. Pulmonary and cardiovascular safety of inhaled insulin in routine practice: The Exubera Large Simple Trial (VOLUME). Contemp Clin Trials Commun. 2019 Aug 13;18:100427. doi: 10.1016/j.conctc.2019.100427. eCollection 2020 Jun.

  PMID: 32478195 DERIVED

• Kolitsopoulos FM, Gatto NM, Sweetland K, Bracken MB, Jackson N. Implications of product withdrawal on a post-approval pragmatic trial: The VOLUME study experience. Contemp Clin Trials Commun. 2019 Oct 28;16:100477. doi: 10.1016/j.conctc.2019.100477. eCollection 2019 Dec.

  PMID: 31799472 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Insulin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

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

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 31, 2006
• First Posted: August 2, 2006
• Study Start: July 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: April 1, 2009
• Last Updated: February 2, 2010
• Results First Posted: January 27, 2010

Record last verified: 2009-09

Locations

DE (44); US (132); SE (4); PR (1); GB (16)