Diabetes MellitusPhase 4VOLUMENCT00359801
Exubera Large Simple Trial To Evaluate Long-Term Pulmonary And Cardiovascular Safety
A Phase 4 study testing Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care in people with Diabetes Mellitus, run by Pfizer at 197 sites in 5 countries.
Trial summary
The purpose of this study is to evaluate the long-term pulmonary and cardiovascular safety of Exubera in routine clinical practice. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,976 participants
- Where
- 197 sitesin 5 countries
- Study dates
- Jul 2006to Apr 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible for receiving Exubera treatment based on the approved local label
Who cannot join
- Pregnant or lactating
- Have a progressive fatal disease or a life expectancy that prohibits them from participating in a five-year research study
Trial locations and contacts
197 sites in 5 countries.
197 sites in 5 countries
United States132 sites
Pfizer Investigational Site
Albuquerque, New Mexico, 87106
Pfizer Investigational Site
Ann Arbor, Michigan, 48104
Pfizer Investigational Site
Asheboro, North Carolina, 27203
Pfizer Investigational Site
Ashtabula, Ohio, 44004
Pfizer Investigational Site
Atlanta, Georgia, 30318-2513
Pfizer Investigational Site
Atlanta, Georgia, 30342
Pfizer Investigational Site
Auburn, Maine, 04210
Pfizer Investigational Site
Babylon, New York, 11702
Pfizer Investigational Site
Baltimore, Maryland, 21204
Pfizer Investigational Site
Battle Creek, Michigan, 49014
Pfizer Investigational Site
Battle Creek, Michigan, 49017
Pfizer Investigational Site
Bay Minette, Alabama, 36507-4185
Pfizer Investigational Site
Belleville, New Jersey, 07109
Pfizer Investigational Site
Belvidere, New Jersey, 07823
Pfizer Investigational Site
Bend, Oregon, 97701
Pfizer Investigational Site
Bismarck, North Dakota, 58501
Pfizer Investigational Site
Boca Raton, Florida, 33433
Pfizer Investigational Site
Boise, Idaho, 83704
Pfizer Investigational Site
Bossier City, Louisiana, 71111
Pfizer Investigational Site
Boston, Massachusetts, 02110
Pfizer Investigational Site
Brooklyn, New York, 11224
Pfizer Investigational Site
Broomall, Pennsylvania, 19008
Pfizer Investigational Site
Burnsville, West Virginia, 26335
Pfizer Investigational Site
Canton, Ohio, 44708
Pfizer Investigational Site
Charleston, South Carolina, 29412
Pfizer Investigational Site
Charleston, West Virginia, 25314
Pfizer Investigational Site
Charlotte, North Carolina, 28227
Pfizer Investigational Site
Chesapeake, Virginia, 23320
Pfizer Investigational Site
Clearwater, Florida, 33756
Pfizer Investigational Site
Cleveland, Ohio, 44113
Pfizer Investigational Site
Clinton, Michigan, 49236
Pfizer Investigational Site
Clinton, Oklahoma, 73601
Pfizer Investigational Site
Columbus, Ohio, 43207
Pfizer Investigational Site
Conyers, Georgia, 30013
Pfizer Investigational Site
Corpus Christi, Texas, 78414
Pfizer Investigational Site
Cudahy, California, 90201
Pfizer Investigational Site
Dauphin, Pennsylvania, 17018
Pfizer Investigational Site
Dayton, Ohio, 45419
Pfizer Investigational Site
DeBary, Florida, 32713
Pfizer Investigational Site
Decatur, Georgia, 30035
Pfizer Investigational Site
Denver, Colorado, 80219
Pfizer Investigational Site
Des Moines, Iowa, 50315
Pfizer Investigational Site
El Cajon, California, 92019
Pfizer Investigational Site
Elkton, Maryland, 21921
Pfizer Investigational Site
Ettrick, Virginia, 23803
Pfizer Investigational Site
Fairhope, Alabama, 36532
Pfizer Investigational Site
Fishers, Indiana, 46038
Pfizer Investigational Site
Flint, Michigan, 48504
Pfizer Investigational Site
Florence, South Carolina, 29501
Pfizer Investigational Site
Fogelsville, Pennsylvania, 18051
Pfizer Investigational Site
Forrest City, Arkansas, 72335
Pfizer Investigational Site
Gainesville, Florida, 32605
Pfizer Investigational Site
Garland, Texas, 75041
Pfizer Investigational Site
Germantown, Tennessee, 38138
Pfizer Investigational Site
Glen Burnie, Maryland, 21061
Pfizer Investigational Site
Glendora, New Jersey, 08029
Pfizer Investigational Site
Grand Island, Nebraska, 68803
Pfizer Investigational Site
Graysville, Alabama, 35073
Pfizer Investigational Site
Green Cove Springs, Florida, 32043
Pfizer Investigational Site
Greenville, Illinois, 62246
Pfizer Investigational Site
Greer, South Carolina, 29651
Pfizer Investigational Site
Hanover, Pennsylvania, 17331
Pfizer Investigational Site
Harrisburg, Pennsylvania, 17112
Pfizer Investigational Site
Hollywood, Florida, 33021
Pfizer Investigational Site
Huntington Beach, California, 92648
Pfizer Investigational Site
Hurst, Texas, 76054
Pfizer Investigational Site
Incline Village, Nevada, 89452
Pfizer Investigational Site
Indianapolis, Indiana, 46229
Pfizer Investigational Site
Indianapolis, Indiana, 46254-5472
Pfizer Investigational Site
Jeannette, Pennsylvania, 15644
Pfizer Investigational Site
Jenkintown, Pennsylvania, 19046
Pfizer Investigational Site
Jersey Shore, Pennsylvania, 17740
Pfizer Investigational Site
Kaufman, Texas, 75142
Pfizer Investigational Site
Kissimmee, Florida, 34741
Pfizer Investigational Site
Kissimmee, Florida, 34743
Pfizer Investigational Site
Layton, Utah, 84041
Pfizer Investigational Site
Libertyville, Illinois, 60048
Pfizer Investigational Site
Louisville, Kentucky, 40258
Pfizer Investigational Site
Lubbock, Texas, 79410
Pfizer Investigational Site
Marianna, Florida, 32446
Pfizer Investigational Site
McConnelsville, Ohio, 43756
Pfizer Investigational Site
Merritt Island, Florida, 32952
Pfizer Investigational Site
Miami, Florida, 33144
Pfizer Investigational Site
Midland, Texas, 79705
Pfizer Investigational Site
Milford, Connecticut, 06460
Pfizer Investigational Site
Morehead City, North Carolina, 28557-3126
Pfizer Investigational Site
Mount Sterling, Kentucky, 40353
Pfizer Investigational Site
Muskegon, Michigan, 49444
Pfizer Investigational Site
New Hartford, New York, 13413
Pfizer Investigational Site
Niceville, Florida, 32578
Pfizer Investigational Site
Norristown, Pennsylvania, 19401
Pfizer Investigational Site
North Myrtle Beach, South Carolina, 29582
Pfizer Investigational Site
Opa-locka, Florida, 33054-3818
Pfizer Investigational Site
Orange City, Florida, 32763
Pfizer Investigational Site
Ormond Beach, Florida, 32174
Pfizer Investigational Site
Pell City, Alabama, 35125
Pfizer Investigational Site
Pembroke Pines, Florida, 33027
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19153-2326
Pfizer Investigational Site
Phoenix, Arizona, 85016
Pfizer Investigational Site
Phoenix, Arizona, 85028
Pfizer Investigational Site
Phoenix, Arizona, 85029
Pfizer Investigational Site
Plantation, Florida, 33324
Pfizer Investigational Site
Plymouth, Massachusetts, 02360
Pfizer Investigational Site
Plymouth Meeting, Pennsylvania, 19462
Pfizer Investigational Site
Port Charlotte, Florida, 33952
Pfizer Investigational Site
Raleigh, North Carolina, 27609
Pfizer Investigational Site
Raleigh, North Carolina, 27610
Pfizer Investigational Site
Rochester, New York, 14622
Pfizer Investigational Site
Rolling Hills Estates, California, 90274
Pfizer Investigational Site
Saint Cloud, Minnesota, 56301
Pfizer Investigational Site
San Antonio, Texas, 78229
Pfizer Investigational Site
San Jose, California, 95116
Pfizer Investigational Site
San Marcos, Texas, 78666
Pfizer Investigational Site
Santa Ana, California, 92704
Pfizer Investigational Site
Searcy, Arkansas, 72143
Pfizer Investigational Site
Shelby, North Carolina, 28150
Pfizer Investigational Site
Stephenville, Texas, 76401
Pfizer Investigational Site
Sterling Heights, Michigan, 48310
Pfizer Investigational Site
Tabor City, North Carolina, 28463
Pfizer Investigational Site
Tampa, Florida, 33607
Pfizer Investigational Site
Tampa, Florida, 33624
Pfizer Investigational Site
Tipton, Pennsylvania, 16684
Pfizer Investigational Site
Troy, Michigan, 48084
Pfizer Investigational Site
Warner Robins, Georgia, 31088
Pfizer Investigational Site
Warren, Michigan, 48091
Pfizer Investigational Site
Webster, Texas, 77598
Pfizer Investigational Site
Westminster, California, 92683
Pfizer Investigational Site
Wheaton, Maryland, 20902
Pfizer Investigational Site
Williamsville, New York, 14221
Pfizer Investigational Site
Wilmington, Delaware, 19806
Pfizer Investigational Site
Winston-Salem, North Carolina, 27103
Pfizer Investigational Site
Zanesville, Ohio, 43701
Germany44 sites
Pfizer Investigational Site
Aschaffenburg, 63739
Pfizer Investigational Site
Bad Doberan, 18209
Pfizer Investigational Site
Bad Grönenbach, 87730
Pfizer Investigational Site
Bad Oeynhausen, 32549
Pfizer Investigational Site
Bad Staffelstein, 96231
Pfizer Investigational Site
Berlin, 12247
Pfizer Investigational Site
Berlin, 13355
Pfizer Investigational Site
Bonn, 53179
Pfizer Investigational Site
Chemnitz, 09130
Pfizer Investigational Site
Cologne, 51069
Pfizer Investigational Site
Datteln, 45711
Pfizer Investigational Site
Dortmund, 44137
Pfizer Investigational Site
Dortmund, 44339
Pfizer Investigational Site
Eisenach, 99817
Pfizer Investigational Site
Emden, 26725
Pfizer Investigational Site
Essen, 45329
Pfizer Investigational Site
Esslingen am Neckar, 73728
Pfizer Investigational Site
Falkensee, 14612
Pfizer Investigational Site
Friedberg, 86316
Pfizer Investigational Site
Fulda, 36037
Pfizer Investigational Site
Hagen, 58091
Pfizer Investigational Site
Hamburg, 21073
Pfizer Investigational Site
Hamburg, 22041
Pfizer Investigational Site
Hohenmölsen, 06679
Pfizer Investigational Site
Jena, 07743
Pfizer Investigational Site
Leverkusen, 51371
Pfizer Investigational Site
Mahlberg, 77972
Pfizer Investigational Site
Mannheim, 68161
Pfizer Investigational Site
Markdorf, 88677
Pfizer Investigational Site
Marl, 45770
Pfizer Investigational Site
Meissen, 01662
Pfizer Investigational Site
Münster, 48145
Pfizer Investigational Site
Münster, 48153
Pfizer Investigational Site
Neuwied, 56564
Pfizer Investigational Site
Nuremberg, 90480
Pfizer Investigational Site
Reinfeld, 23858
Pfizer Investigational Site
Riesa, 01587
Pfizer Investigational Site
Schlüchtern, 36381
Pfizer Investigational Site
Siegen, 57072
Pfizer Investigational Site
Suhl, 98529
Pfizer Investigational Site
Villingen-Schwenningen, 78054
Pfizer Investigational Site
Wangen, 88239
Pfizer Investigational Site
Wangen I. Allgaeu, 88239
Pfizer Investigational Site
Warburg, 34414
United Kingdom16 sites
Pfizer Investigational Site
Airdrie, ML6 0JS
Pfizer Investigational Site
Ashford, Middlesex, TW15 3EA
Pfizer Investigational Site
Bath, BA2 3HT
Pfizer Investigational Site
Bath, BA2 4BY
Pfizer Investigational Site
Birmingham, B37 7TR
Pfizer Investigational Site
Chesterfield, Derbyshire, S40 4TF
Pfizer Investigational Site
Dronfield, Sheffield, S18 1RU
Pfizer Investigational Site
Leicester, LE1 5WW
Pfizer Investigational Site
Newcastle upon Tyne, NE15 6TQ
Pfizer Investigational Site
Newcastle upon Tyne, NE3 3QJ
Pfizer Investigational Site
Rugby, Warwickshire, CV22 5PX
Pfizer Investigational Site
Sheffield, Yorkshire, S7 2DW
Pfizer Investigational Site
Warminster, WILTSHIRE, BA12 9AA
Pfizer Investigational Site
Westbury, BA13 3JD
Pfizer Investigational Site
Weybridge, SURREY, KT15 2BH
Pfizer Investigational Site
Woking, Surrey, GU22 7EY
Sweden4 sites
Pfizer Investigational Site
Borås, 503 30
Pfizer Investigational Site
Forshaga, 667 32
Pfizer Investigational Site
Gothenburg, 41345
Pfizer Investigational Site
Lilla Edet, 46330
About this study
Official title: An International, Multicenter, Large Simple Trial To Evaluate The Long-Term Pulmonary And Cardiovascular Safety Of Exubera In Patients With Diabetes Mellitus
The purpose of this study is to evaluate the long-term pulmonary and cardiovascular safety of Exubera in routine clinical practice.
Read the 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.
- Conditions
- Diabetes Mellitus
- Being tested
- Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care
- Keywords
- Large Simple Trial
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes CareDrug
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.
Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes CareDrug
Also called Non-Exubera
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).
| Study group | Role | What they receive |
|---|---|---|
| Exubera | Experimental | Not described Receives: Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care |
| Usual Diabetes Care | Active comparator | Not described Receives: Drug: Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline to 5 years
Secondary outcomes (11)
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
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.
Measured: 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
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.
Measured: 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
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.
Measured: Baseline to 5 years
All-cause Mortality: Number of Deaths
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.
Measured: Baseline through End of Study
Time to Event: All-cause Mortality
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.
Measured: Baseline to 5 years
Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke
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.
Measured: Baseline through End of Study
Time to Event for Cardiovascular Serious Adverse Event (SAE) Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction, or Non-fatal Stroke
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.
Measured: Baseline to 5 years
Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm
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.
Measured: Baseline through End of Study
Time to Event for Allergic Response Serious Adverse Event (SAE) Composite, Including: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm
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.
Measured: Baseline to 5 years
Change in Glycosylated Hemoglobin (HbA1c) From Baseline
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.
Measured: Baseline, Month 6, Year 1, Year 2, Index Visit
Change in Glycosylated Hemoglobin (HbA1c) From Baseline
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.
Measured: Baseline to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2006 (estimated)
- Study startJul 2006
- Primary completionDec 2008
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,976 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00359801
- Sponsor's protocol ID
- A2171069
- Acronym
- VOLUME
- Status last verified
- Sep 2009
- First submitted
- 31 Jul 2006
- Last updated
- 2 Feb 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 32478195Kolitsopoulos 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.
PubMed 31799472
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International, Multicenter, Large Simple Trial To Evaluate The Long-Term Pulmonary And Cardiovascular Safety Of Exubera In Patients With Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00359801
- Acronym / sponsor ID
- VOLUME / A2171069
- Conditions
- Diabetes Mellitus
- Keywords
- Large Simple Trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,976 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jul 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 2 Aug 2006 (estimated)
- Results
- Posted 27 Jan 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the long-term pulmonary and cardiovascular safety of Exubera in routine clinical practice.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Eligible for receiving Exubera treatment based on the approved local label
Key exclusion criteria (2 listed)
- Pregnant or lactating
- Have a progressive fatal disease or a life expectancy that prohibits them from participating in a five-year research study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes CareSubjects 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. | Drug | Exubera |
| Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes CareAlso: Non-ExuberaSubjects 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). | Drug | Usual Diabetes Care |
Primary outcome
Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline
Time frame: 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.
Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects
Time frame: 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.
Time to Persistent Decline in FEV1 Exceeding 20% From Baseline
Time frame: 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.
11 secondary outcomes
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Time frame: 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
Time frame: 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
Time frame: Baseline to 5 years
All-cause Mortality: Number of Deaths
Time frame: Baseline through End of Study
Time to Event: All-cause Mortality
Time frame: Baseline to 5 years
Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke
Time frame: Baseline through End of Study
Time to Event for Cardiovascular Serious Adverse Event (SAE) Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction, or Non-fatal Stroke
Time frame: Baseline to 5 years
Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm
Time frame: Baseline through End of Study
Time to Event for Allergic Response Serious Adverse Event (SAE) Composite, Including: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm
Time frame: Baseline to 5 years
Change in Glycosylated Hemoglobin (HbA1c) From Baseline
Time frame: Baseline, Month 6, Year 1, Year 2, Index Visit
Change in Glycosylated Hemoglobin (HbA1c) From Baseline
Time frame: Baseline to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32478195Gatto 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.
- Derived from this study: PubMed 31799472Kolitsopoulos 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
197 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Randomization to Exubera (insulin human [rDNA origin] inhalation powder) or Usual Diabetes Care in people with Diabetes Mellitus, run by Pfizer at 197 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 197 sites in United States, Germany, United Kingdom, Sweden, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline (time frame: Baseline, Month 6, Year 1, Year 2, Index Visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00359801, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2010.