Long-Term Safety Study of Inhaled Insulin: An Up to Four-Year Extension of Therapy in Subjects With Type 1 or Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a long-term safety study for Phase 2 subjects who choose to remain on Exubera® (inhaled insulin).

Detailed Description
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The study was terminated on Oct. 18, 2007. This study is not a post approval commitment study. Pfizer decided to cancel new trials because of the decision to withdraw Exubera® (inhaled insulin) due to lack of market performance and not for safety reasons.

Official Title
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An Open-Label, Phase 2, Long-Term Safety Study of Inhaled Insulin: An Up to Four-Year Extension of Therapy in Subjects With Type 1 or Type 2 Diabetes Mellitus Participating in Extension Protocols 217-102, 103, or 104

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Exubera® (inhaled insulin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Type 1 or Type 2 Diabetes Mellitus who participated in previous Phase 2 extension protocols Exclusion Criteria: Smoking Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exubera® (inhaled insulin)<br>Open label, no comparator | Drug: Exubera® (inhaled insulin)<br>* Treatment of type 1 and type 2 diabetes with short-acting insulin<br>* Other names: Exubera®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment | Change from Baseline: mean of (value of observed forced expiratory volume in 1 second (FEV1) (liters) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements. | Baseline to 126 months | 
| Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment | Change from Baseline: mean of (value of observed Carbon Monoxide Diffusing Capacity (mL/min/mm Hg) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements. | baseline to 126 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Hemoglobin by Duration of Exubera Treatment | Change from Baseline: mean of (value of observed glycosylated hemoglobin (HbA1C) (percent) at treatment duration minus baseline value). Duration of treatment is based on the elapsed duration of treatment in the controlled and uncontrolled studies. Baseline was based on pre-inhaled insulin measurements. | Baseline to 126 months | 
| Hypoglycemic Event Rates by Interval of Exubera Treatment | Number of hypoglycemic events per subject-month. Subject-month determined by time on treatment. Interval of treatment based on elapsed duration of treatment in the controlled & uncontrolled studies.Overall represents entire duration of treatment. Hypoglycemia: Characteristic symptoms of hypoglycemia with no blood glucose check. Clinical picture must include prompt resolution with food intake, subcutaneous glucagon or intravenous glucose.OR,Characteristic symptoms of hypoglycemia with blood glucose check showing glucose <=59 mg/dl.OR,Any glucose measurement <=49 mg/dl,with or without symptoms. | 0 to 132 months | 
| Severe Hypoglycemic Event Rates by Interval of Exubera Treatment | Number of severe hypoglycemic events per 100 subject-months.Subject-month determined by time on treatment.Interval of treatment based on elapsed duration of treatment in controlled & uncontrolled studies.Overall represents entire duration of treatment.A severe hypoglycemic event must have met all 3of following:1.subject unable to treat self.2.subject exhibited 1 or more of neurological symptoms defined in protocol.3.blood glucose must be <=49 mg/dl if measured.If not measured,clinical manifestations must have been reversed by oral carbohydrates,subcutaneous glucagon,or intravenous glucose. | 0-132 months | 
| Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes | Observed values by duration of treatment. | 36 months to 126 months | 
| Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry) | observed values by duration of treatment. | 36 to 126 months | 
| Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry) | Observed values by duration of treatment. | 6 to 120 months | 
| Number of Decliners in Either Forced Expiratory Volume in 1 Second (L) or Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg), by Duration of Exubera Treatment | Decliners = decline of ≥15% in forced expiratory volume or ≥20% in carbon monoxide diffusing capacity. | 3 to >=108 months | 
| Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment | Decliners at particular timepoint were defined as any decline of ≥15% in forced expiratory volume. | 3 to >=108 months | 
| Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment | Decliners at particular timepoint were defined as any decline of ≥20% in carbon monoxide diffusing capacity. | 6 to >=108 months |