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

• Change in Forced Expiratory Volume in 1 Second (L) by Time on Exubera Treatment [ Time Frame: Baseline to 126 months ] [ Designated as safety issue: Yes ]
  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.
  
  
• Change in Carbon Monoxide Diffusing Capacity (mL/Min/mm Hg) by Time on Exubera Treatment [ Time Frame: baseline to 126 months ] [ Designated as safety issue: Yes ]
  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.
  
  

• Change in Glycosylated Hemoglobin by Duration of Exubera Treatment [ Time Frame: Baseline to 126 months ] [ Designated as safety issue: No ]
  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.
  
  
• Hypoglycemic Event Rates by Interval of Exubera Treatment [ Time Frame: 0 to 132 months ] [ Designated as safety issue: No ]
  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.
  
  
• Severe Hypoglycemic Event Rates by Interval of Exubera Treatment [ Time Frame: 0-132 months ] [ Designated as safety issue: No ]
  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.
  
  
• Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 1 Diabetes [ Time Frame: 36 months to 126 months ] [ Designated as safety issue: Yes ]
  Observed values by duration of treatment.
  
  
• Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Using Insulin at Study Entry) [ Time Frame: 36 to 126 months ] [ Designated as safety issue: Yes ]
  observed values by duration of treatment.
  
  
• Insulin Antibodies (Percent Binding) by Time on Exubera Treatment - Subjects With Type 2 Diabetes (Not Using Insulin at Study Entry) [ Time Frame: 6 to 120 months ] [ Designated as safety issue: Yes ]
  Observed values by duration of treatment.
  
  
• 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 [ Time Frame: 3 to >=108 months ] [ Designated as safety issue: Yes ]
  Decliners = decline of ≥15% in forced expiratory volume or ≥20% in carbon monoxide diffusing capacity.
  
  
• Number of Decliners in Forced Expiratory Volume in 1 Second (L) by Duration of Exubera Treatment [ Time Frame: 3 to >=108 months ] [ Designated as safety issue: Yes ]
  Decliners at particular timepoint were defined as any decline of ≥15% in forced expiratory volume.
  
  
• Number of Decliners in Carbon Monoxide Diffusing Capacity (ml/Min/mm Hg) by Duration of Exubera Treatment [ Time Frame: 6 to >=108 months ] [ Designated as safety issue: Yes ]
  Decliners at particular timepoint were defined as any decline of ≥20% in carbon monoxide diffusing capacity.
  
  

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.