Diabetes Mellitus
Conditions
Keywords
Large Simple Trial
Brief summary
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.
Interventions
DRUGRandomization 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.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Germany, Puerto Rico, Sweden, United Kingdom, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Exubera® Exubera® plus usual diabetes care | 987 |
| Non-Exubera® Usual diabetes care | 989 |
| Total | 1,976 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Final Status Unknown: missing data | 7 | 4 |
| Overall Study | Lost to Follow-up | 72 | 58 |
| Overall Study | Other | 66 | 46 |
| Overall Study | Sponsor Decision | 17 | 16 |
| Overall Study | Withdrawal by Subject | 143 | 96 |
Baseline characteristics
| Characteristic | Exubera® | Non-Exubera® | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 114 participants | 133 participants | 247 participants |
| Age, Customized 45-64 years | 576 participants | 552 participants | 1128 participants |
| Age, Customized 65-74 years | 242 participants | 245 participants | 487 participants |
| Age, Customized 75-84 years | 52 participants | 57 participants | 109 participants |
| Age, Customized >= 85 years | 3 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 439 Participants | 434 Participants | 873 Participants |
| Sex: Female, Male Male | 548 Participants | 555 Participants | 1103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 987 | 11 / 989 |
| serious Total, serious adverse events | 124 / 987 | 109 / 989 |
Outcome results
Primary
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.
Time frame: Baseline, Month 6, Year 1, Year 2, Index Visit
Population: Full Analysis Set: all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Initial FEV1 Decline but not a Confirmed Decline | 81 participants |
| Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Confirmed FEV1 Decline but not Persistent Decline | 11 participants |
| Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Confirmed FEV1 Decline | 19 participants |
| Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Persistent FEV1 Decline | 8 participants |
| Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Initial FEV1 Decline | 100 participants |
| Non-Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Persistent FEV1 Decline | 0 participants |
| Non-Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Initial FEV1 Decline | 112 participants |
| Non-Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Initial FEV1 Decline but not a Confirmed Decline | 105 participants |
| Non-Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Confirmed FEV1 Decline | 7 participants |
| Non-Exubera® | Number of Subjects With Decline in Forced Expiratory Volume (FEV1) Exceeding 20% From Baseline | Confirmed FEV1 Decline but not Persistent Decline | 7 participants |
Primary
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.
Time frame: Baseline, Month 6, Year 1, Year 2, Index Visit
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Confirmed FEV1 Decline | 38 participants |
| Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Initial FEV1 Decline but not a Confirmed Decline | 62 participants |
| Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Confirmed FEV1 Decline but not Persistent Decline | 11 participants |
| Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Persistent FEV1 Decline | 27 participants |
| Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Initial FEV1 Decline | 100 participants |
| Non-Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Persistent FEV1 Decline | 24 participants |
| Non-Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Initial FEV1 Decline | 112 participants |
| Non-Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Initial FEV1 Decline but not a Confirmed Decline | 74 participants |
| Non-Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Confirmed FEV1 Decline | 38 participants |
| Non-Exubera® | Supplemental Definition of Decline in Forced Expiratory Volume in One Second (FEV1): Number of Subjects | Confirmed FEV1 Decline but not Persistent Decline | 14 participants |
Primary
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.
Time frame: Baseline to 5 years
Population: FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.
Secondary
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.
Time frame: Baseline through End of Study
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exubera® | All-cause Mortality: Number of Deaths | 12 participants |
| Non-Exubera® | All-cause Mortality: Number of Deaths | 9 participants |
Secondary
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.
Time frame: Baseline through End of Study
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exubera® | Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm | Definite or Possible | 2 events |
| Exubera® | Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm | Insufficient | 3 events |
| Non-Exubera® | Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm | Definite or Possible | 0 events |
| Non-Exubera® | Allergic Response Serious Adverse Event (SAE) Composite: SAEs of Anaphylaxis, Angioedema, Generalized Allergic Reaction, or Allergic Bronchospasm | Insufficient | 0 events |
Secondary
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.
Time frame: Baseline through End of Study
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Definite or Possible | 10 events |
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Insufficient | 9 events |
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Other (non-myocardial infarction, non-stroke) | 15 events |
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Death from Cardiovascular or Cerebrovascular | 2 events |
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Definite | 5 events |
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Definite or Possible, or Death from Cardiovascular | 12 events |
| Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Possible | 5 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Definite or Possible, or Death from Cardiovascular | 11 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Possible | 6 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Definite | 3 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Other (non-myocardial infarction, non-stroke) | 9 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Definite or Possible | 9 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Insufficient | 7 events |
| Non-Exubera® | Cardiovascular SAE Composite: SAEs of Cardiovascular Mortality, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke | Death from Cardiovascular or Cerebrovascular | 4 events |
Secondary
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.
Time frame: Baseline, Week 26, Week 52, Week 104, Index Visit
Population: FAS; (n) = number of subjects with analyzable data at observation for Exubera® and Non-Exubera®, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Week 26 (n=813, 852) | -0.009 liters | Standard Deviation 0.568 |
| Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Week 104 (n=3, 1) | -0.103 liters | Standard Deviation 0.607 |
| Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Week 52 (n=470, 482) | -0.032 liters | Standard Deviation 0.411 |
| Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Index Visit (n=729, 803) | -0.000 liters | Standard Deviation 0.559 |
| Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline (n=985, 987) | 2.661 liters | Standard Deviation 0.838 |
| Non-Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Index Visit (n=729, 803) | -0.018 liters | Standard Deviation 0.58 |
| Non-Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline (n=985, 987) | 2.684 liters | Standard Deviation 0.888 |
| Non-Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Week 26 (n=813, 852) | -0.035 liters | Standard Deviation 0.509 |
| Non-Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Week 52 (n=470, 482) | -0.056 liters | Standard Deviation 0.465 |
| Non-Exubera® | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Week 104 (n=3, 1) | -1.270 liters | Standard Deviation 0 |
Secondary
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.
Time frame: Baseline, Month 6, Year 1, Year 2, Index Visit
Population: FAS; (n) = number of subjects with analyzable data at observation for Exubera® and Non-Exubera®, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 26: Observed Value (804, 849) | 8.0 percent | Standard Deviation 1.8 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 104: Observed Value (n=3, 1) | 6.6 percent | Standard Deviation 1.2 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Baseline (n=978, 985) | 8.6 percent | Standard Deviation 1.9 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 104: Change from Baseline (n=3, 1) | -1.0 percent | Standard Deviation 1.6 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 52: Observed Value (n=468, 489) | 7.8 percent | Standard Deviation 1.7 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Index Visit: Observed Value (n=673, 754) | 8.1 percent | Standard Deviation 3 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 26: Change from Baseline (n=800, 848) | -0.5 percent | Standard Deviation 1.7 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Index Visit: Change from Baseline (n=669, 754) | -0.3 percent | Standard Deviation 2.9 |
| Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 52: Change from Baseline (n=467, 489) | -0.4 percent | Standard Deviation 1.6 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Index Visit: Change from Baseline (n=669, 754) | -0.5 percent | Standard Deviation 3.3 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Baseline (n=978, 985) | 8.5 percent | Standard Deviation 1.9 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 26: Change from Baseline (n=800, 848) | -0.5 percent | Standard Deviation 1.6 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 52: Observed Value (n=468, 489) | 7.7 percent | Standard Deviation 1.6 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 52: Change from Baseline (n=467, 489) | -0.6 percent | Standard Deviation 1.6 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 104: Observed Value (n=3, 1) | 6.0 percent | Standard Deviation 0 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 104: Change from Baseline (n=3, 1) | -2.7 percent | Standard Deviation 0 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Index Visit: Observed Value (n=673, 754) | 8.0 percent | Standard Deviation 3.5 |
| Non-Exubera® | Change in Glycosylated Hemoglobin (HbA1c) From Baseline | Week 26: Observed Value (804, 849) | 8.0 percent | Standard Deviation 1.8 |
Secondary
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.
Time frame: Baseline to 5 years
Population: FAS. Due to early study termination, the originally planned inferential analysis (linear model) for change from baseline was not done.
Secondary
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.
Time frame: Baseline through End of Study
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Definite | 4 events |
| Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Possible | 3 events |
| Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Definite or Possible | 7 events |
| Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Insufficient | 4 events |
| Non-Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Insufficient | 2 events |
| Non-Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Definite | 1 events |
| Non-Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Definite or Possible | 3 events |
| Non-Exubera® | Pulmonary Serious Adverse Event (SAE) Composite: SAEs of Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pneumonia, or Acute Bronchitis | Possible | 2 events |
Secondary
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.
Time frame: Baseline to 5 years
Population: FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.
Secondary
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.
Time frame: Baseline to 5 years
Population: FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.
Secondary
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.
Time frame: Baseline to 5 years
Population: FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.
Secondary
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.
Time frame: Baseline to 5 years
Population: FAS. Due to early study termination, originally planned inferential analysis for time to event was not done.