Diabetes Mellitus
Conditions
Keywords
Observational Study Exubera
Brief summary
In studies of Exubera in persons with diabetes, lung cancer occurred in a few more people who were taking Exubera than in people who were taking other diabetes medicines. All subjects diagnosed with lung cancer had a history of smoking and the number of lung cancer cases observed fell within the expected range based on population-based data. There is currently not enough information to determine if any of the observed lung cancer cases were related to Exubera use, therefore, the study is being conducted to further investigate whether Exubera use makes the appearance of lung cancer more likely.
Detailed description
Both retrospective and prospective components All subjects who participated in one of the 17 included Exubera clinical trials will be invited to participate in the current study.
Interventions
DRUGExubera
Subjects who had been treated with Exubera in a prior Exubera controlled trial. Following initial use of randomized treatment, physicians and subjects were free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice).
OTHERRandomized diabetes therapy
Subjects who had been treated with a comparator (other diabetes treatment including one or more of: subcutaneous insulin, sulfonylureas, biguanides, or thiazolinediones) in a prior Exubera controlled trial. Following initial use of randomized treatment, physicians and subjects were free to change regimens and dosing based on subject response to assigned treatment (as consistent with routine practice).
Sponsors
Pfizer
Study design
Observational model
COHORT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously participated in an eligible Exubera clinical trial * Willing to provide study doctor with at least one alternate contact person
Exclusion criteria
* Participated in an investigational study of an unapproved drug since completing the Exubera trial * Ever used an other (non-Exubera) inhaled insulin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Primary Lung Cancer Mortality | Baseline from original trial up to Year 2 of this study | Reported deaths from primary lung cancer were adjudicated and classified into 4 categories: highly likely (clinical, radiographic, and/or histological data consistent with primary lung cancer); likely (some information may have been missing for definite diagnosis); unlikely; insufficient information. Highly likely and likely cases used to report rate and rate ratio of primary lung cancer mortality. Includes events from the start of the original trial to the end of FUSE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Primary Lung Cancer Mortality Among Former Smokers | Baseline from original trial up to Year 2 of this study | Reported deaths from primary lung cancer were adjudicated and classified into 4 categories: highly likely (clinical, radiographic, and/or histological data consistent with primary lung cancer); likely (some information may have been missing for definite diagnosis); unlikely; insufficient information. Highly likely and likely cases used to report rate and rate ratio of primary lung cancer mortality. Includes events from the start of the original trial to the end of FUSE. |
| Rate of All-cause Mortality | Baseline from original trial up to Year 2 of this study | The rate and rate ratio of all-cause mortality that occurred anytime from the start of the original trial to the end of FUSE. |
| Rate of Primary Lung Cancer Diagnosis | Baseline from original trial up to Year 2 of this study | The rate and rate ratio of lung cancer adjudicated as highly likely (clinical, radiographic, and/or histological data consistent with primary lung cancer) or likely (some information may have been missing for definite diagnosis) to be newly diagnosed primary lung cancer that occurred anytime from the start of the original trial to the end of FUSE. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Italy, Mexico, Netherlands, Norway, Poland, Portugal, Slovakia, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This study had retrospective and prospective components. Individuals who participated in Exubera-controlled trials that were still active in 2003 or later participated in the retrospective part of this study (Follow-Up Study for Exubera; FUSE). Individuals from sites participating in the prospective part of FUSE were eligible.
Participants by arm
| Arm | Count |
|---|---|
| Previously Randomized to Exubera Participants randomized to Exubera® (inhalable form of recombinant human \[rh\] insulin) per protocol in a prior Exubera-controlled clinical trial. There was no active study medication used in FUSE. During prospective follow-up all participants received treatment for diabetes mellitus per routine clinical practice. | 3,875 |
| Previously Randomized to Comparator Participants randomized to comparator (Type 1 or Type 2 diabetes mellitus treatments such as injected insulin or oral agent therapy) in a prior Exubera-controlled trial. There was no active study medication used in FUSE. During prospective follow-up all participants received treatment for diabetes mellitus per routine clinical practice. | 3,564 |
| Total | 7,439 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Prospective Period | Lost to Follow-up | 37 | 33 |
| Prospective Period | Other | 2 | 2 |
| Prospective Period | Study Terminated | 1 | 0 |
| Prospective Period | Withdrawal by Subject | 11 | 9 |
| Screening for Prospective Period | Patient at partic. site not enrolled | 913 | 803 |
| Screening for Prospective Period | Site did not participate | 1,604 | 1,488 |
Baseline characteristics
| Characteristic | Previously Randomized to Comparator | Previously Randomized to Exubera | Total |
|---|---|---|---|
| Age Continuous | 54.7 years STANDARD_DEVIATION 12.6 | 54.8 years STANDARD_DEVIATION 12.1 | 54.8 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 1557 Participants | 1677 Participants | 3234 Participants |
| Sex: Female, Male Male | 2007 Participants | 2198 Participants | 4205 Participants |
| Smoking status Ever-smoker | 1533 participants | 1681 participants | 3214 participants |
| Smoking status Never-smoker | 2031 participants | 2194 participants | 4225 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Rate of Primary Lung Cancer Mortality
Reported deaths from primary lung cancer were adjudicated and classified into 4 categories: highly likely (clinical, radiographic, and/or histological data consistent with primary lung cancer); likely (some information may have been missing for definite diagnosis); unlikely; insufficient information. Highly likely and likely cases used to report rate and rate ratio of primary lung cancer mortality. Includes events from the start of the original trial to the end of FUSE.
Time frame: Baseline from original trial up to Year 2 of this study
Population: Entire study population: all randomized participants (retrospective).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Previously Randomized to Exubera | Rate of Primary Lung Cancer Mortality | 0.48 Deaths per 1000 patient years (PY) |
| Previously Randomized to Comparator | Rate of Primary Lung Cancer Mortality | 0.17 Deaths per 1000 patient years (PY) |
95% CI: [0.5, 28.46]
Secondary
Rate of All-cause Mortality
The rate and rate ratio of all-cause mortality that occurred anytime from the start of the original trial to the end of FUSE.
Time frame: Baseline from original trial up to Year 2 of this study
Population: Entire study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Previously Randomized to Exubera | Rate of All-cause Mortality | 6.03 Deaths per 1000 PY |
| Previously Randomized to Comparator | Rate of All-cause Mortality | 7.37 Deaths per 1000 PY |
95% CI: [0.6, 1.1]
Secondary
Rate of Primary Lung Cancer Diagnosis
The rate and rate ratio of lung cancer adjudicated as highly likely (clinical, radiographic, and/or histological data consistent with primary lung cancer) or likely (some information may have been missing for definite diagnosis) to be newly diagnosed primary lung cancer that occurred anytime from the start of the original trial to the end of FUSE.
Time frame: Baseline from original trial up to Year 2 of this study
Population: Entire study population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Previously Randomized to Exubera | Rate of Primary Lung Cancer Diagnosis | 1.07 Lung Cancer per 1000 PY |
| Previously Randomized to Comparator | Rate of Primary Lung Cancer Diagnosis | 0.29 Lung Cancer per 1000 PY |
95% CI: [1.01, 20.68]
Secondary
Rate of Primary Lung Cancer Mortality Among Former Smokers
Reported deaths from primary lung cancer were adjudicated and classified into 4 categories: highly likely (clinical, radiographic, and/or histological data consistent with primary lung cancer); likely (some information may have been missing for definite diagnosis); unlikely; insufficient information. Highly likely and likely cases used to report rate and rate ratio of primary lung cancer mortality. Includes events from the start of the original trial to the end of FUSE.
Time frame: Baseline from original trial up to Year 2 of this study
Population: Subset of the entire study population who were former smokers.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Previously Randomized to Exubera | Rate of Primary Lung Cancer Mortality Among Former Smokers | 0.94 Deaths per 1000 PY |
| Previously Randomized to Comparator | Rate of Primary Lung Cancer Mortality Among Former Smokers | 0.41 Deaths per 1000 PY |
95% CI: [0.37, 24.01]