Efficacy and Safety of Inhaled Insulin Compared With Subcutaneous Human Insulin Therapy in Adults With Type 1 Diabetes

• ClinicalTrials.gov Identifier: NCT00137046
• Recruitment Status: Terminated
• First Posted: August 29, 2005
• Results First Posted: January 26, 2010
• Last Update Posted: February 18, 2010
• Sponsor: Pfizer
• Information provided by: Pfizer

Tracking Information

• First Submitted Date: August 26, 2005
• First Posted Date: August 29, 2005
• Results First Submitted Date: December 7, 2009
• Results First Posted Date: January 26, 2010
• Last Update Posted Date: February 18, 2010
• Study Start Date: May 2002
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2009)

• Change From Baseline in Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Baseline through Extension Follow-up Month 3 ]
  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).
• Summary of ≥ 15% Decliners in Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Month 3 through Extension Follow-up 3 ]
  Number of subjects with a post-baseline Forced Expiratory Volume in One Second (FEV1) decrease of ≥ 15 % [(baseline observed value minus visit observed value)/(baseline observed value) * 100]; in the absence of an obvious intercurrent illness, a repeat FEV1 was performed.
• Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) [ Time Frame: Baseline through Extension Follow-up Month 3 ]
  Change from Baseline: mean of (value of Carbon Monoxide Diffusing Capacity [DLco] measured in milliters/minutes/millimeters of mercury [mL/min/mmHg] at observation minus Baseline value).
• Summary of ≥ 20% Decliners in Carbon Monoxide Diffusing Capacity (DLco). [ Time Frame: Month 3 through Extension Follow-up Month 3 ]
  Number of subjects with a post-baseline Carbon Monoxide Diffusing Capacity (DLco) decrease of ≥ 20% [(baseline observed value minus visit observed value)/(baseline observed value) * 100]; in the absence of an obvious intercurrent illness, a repeat DLco was performed.
• Annual Rate of Change in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Week -2 through Extension Follow-up Month 6 or end of study ]
  Annual rate of change in FEV1 calculated as slope over time [visit] for forced expiratory volume in 1 second measured as liters per year (L/yr).
• Annual Rate of Change in Carbon Monoxide Diffusion Capacity (DLco) [ Time Frame: Week -2 through Extension Follow-up Month 6 or end of study ]
  Annual rate of change in DLco calculated as slope over time (visit) measured as milliliters per minute per millimeters of hemoglobin per year (ml/min/mmHg/yr).

• Original Primary Outcome Measures (submitted: August 26, 2005): The primary outcome is to assess the toleration and safety of EXUBERA® (inhaled insulin) compared to subcutaneous insulin therapy the effects if any on measures of pulmonary function.

Current Secondary Outcome Measures (submitted: December 7, 2009)

• Change From Baseline in Glycosylated Hemoglobin (HbA1c) [ Time Frame: Baseline through Extension Follow-up Month 3 ]
  Change from Baseline: mean of (value of Glycosylated Hemoglobin [HbA1c] at observation minus Baseline value).
• Hypoglycemic Event Rates [ Time Frame: Month 1 through Extension Month 39 ]
  A Hypoglycemic event was identified by characteristic symptoms of hypoglycemia with no blood glucose check with prompt resolution with food intake, subcutaneous glucagon, or intravenouus glucose; characteristic symptoms with blood glucose of 59 milligrams per deciliter (mg/dL) (3.2 mmol/L) or less with blood glucose check; or any glucose measurement of 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Subject months = elapsed number of months a subject was in the study in each time interval. Crude event rate = total events divided by subject month of treatment.
• Severe Hypoglycemic Event Rates [ Time Frame: Month 1 through Extension Month 39 ]
  Severe hypoglycemic event = all 3 of the following criteria were met: subject unable to treat self, exhbited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness); and blood glucose measurement was ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, subcutaneous glucagon, or i.v. glucose. Subject months = elapsed number of months subject was in study in each time interval. Crude event rate = total events divided by subject months * 100.
• Change From Baseline in Fasting Plasma Glucose [ Time Frame: Baseline through Extension Follow-up Month 3 ]
  Change from Baseline: mean of (value of fasting plasma glucose [milligrams per deciliter (mg/dL)] at observation minus Baseline value).
• Change From Baseline Body Weight [ Time Frame: Baseline through Extension Follow-up Month 3 ]
  Body weight: mean Baseline and change from Baseline in kilograms (kg). Change from baseline = mean body weight in kilograms (kg) at observation minus mean baseline body weight.
• Total Daily Long-Acting Insulin Dose (Unadjusted for Body Weight) [ Time Frame: Month 3 through Extension Month 39 ]
  Total Daily Long-Acting Insulin Dose Unadjusted for Body Weight; long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups.
• Total Daily Long-Acting Insulin Dose Adjusted for Body Weight [ Time Frame: Month 3 through Extension Month 39 ]
  Total daily dose of long-acting insulin adjusted for body weight (units per kilogram [kg]). Long-acting insulin included NPH Insulin, Ultralente, and Insulin Glargine for both groups.
• Total Daily Short-Acting Insulin Dose (Unadjusted for Body Weight) [ Time Frame: Month 3 through Extension Month 39 ]
  Total daily dose of short-acting insulin unadjusted for body weight. Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin.
• Total Daily Short-Acting Insulin Dose Adjusted for Body Weight [ Time Frame: Month 3 through Extension Month 39 ]
  Total Daily Short-Acting Insulin Dose adjusted for body weight (milligrams [mg] or units divided by kilograms [kg]). Short-acting insulin (mg) for the Inhaled Insulin group was Inhaled Insulin. Short-acting insulin (unit) for the Subcutaneous Insulin group included Insulin Lispro, Insulin Aspart, and Regular Insulin.
• Baseline Dyspnea Index (BDI) [ Time Frame: Week - 1 ]
  Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI score range 0 (very severe impairment) to 4 (no impairment) scaled to a BDI focal score (0-12). Lower score indicates greater impairment.
• Transition Dyspnea Index (TDI) [ Time Frame: Week 4 through ,Extension Follow-up Month 6 and every 6 months thereafter or end of study ]
  Clinician administered instrument to measure the baseline severity of breathlessness (shortness of breath) in symptomatic patients with 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI score range -3 (major deterioration) to +3 (major improvement); sum of all domains yields the TDI focal score (-9 to +9); lower score indicates greater deterioration. Compared to previous scoring to determine deterioration or improvement.
• Lipids [ Time Frame: Week -4 through Month 24 ]
  Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides measured as milligrams per deciliter (mg/dL).
• Cough Questionnaire [ Time Frame: Week 0 and if indicated through Extension Follow up Month 3 ]
  Subject completed cough questionnaire with reference to the past 4 weeks. Six question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (subcutaneous [SC] or inhaled), and productivity of cough; range 0 (no symptoms) to 4 (severe symptoms). Questionnaire was administered at Week 0 and then at subsequent visits only if cough was identified as an adverse event not explained by a concomitant condition, such as an upper respiratory tract infection.
• Forced Vital Capacity (FVC) [ Time Frame: Week -3 through Extension Follow-up Month 6 or End of Study ]
  Forced Vital Capacity (FVC) measured in liters (L).
• Total Lung Capacity (TLC) [ Time Frame: Week -3 through Extension Follow-up Month 6 or End of Study ]
  Total Lung Capacity measured in liters (L).
• Insulin Antibodies [ Time Frame: Baseline through Extension Month 39 ]
  Median insulin antibodies at each visit measured in micro units per milliliter (microU/mL).

• Original Secondary Outcome Measures (submitted: August 26, 2005): Secondary endpoints include HbA1c, fasting plasma glucose, body weight, lipids, insulin dose, incidence and severity off hypoglycemic episodes, cough questionnaire, and baseline and transition dyspnea index.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Inhaled Insulin Compared With Subcutaneous Human Insulin Therapy in Adults With Type 1 Diabetes
• Official Title: Efficacy and Safety of Exubera (Inhaled Insulin) Compared With Subcutaneous Human Insulin Therapy in Adult Subjects With Type 1 Diabetes Mellitus: A Long-Term, Outpatient, Open-Label, Parallel-Group Comparative Trial

Brief Summary

This study is being done to find out the good and bad effects of a drug that is not approved for sale and the effects if any on measures of pulmonary function in adult males and females with type 1 diabetes mellitus. The drug is called EXUBERA (inhaled insulin).

This study included a 2-year comparative treatment period followed by a 6-month follow-up period during which inhaled insulin-treated subjects were switched back to subcutaneous short-acting insulin. After this follow-up period, all eligible subjects entered a comparative extension period that was to last for 5 years. When the comparative portion of the study was terminated, all subjects were requested to return for a final extension follow-up month 3 visit.

• Detailed Description: Pfizer announced in October 2007 that it would stop marketing Exubera. 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, study A2171022 was terminated on June 9, 2008. Neither safety nor efficacy reasons were the cause of the study termination.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 1

Intervention

• Drug: Subcutaneous Insulin
  Subcutaneous insulin with dose adjusted according to premeal blood glucose
• Drug: Inhaled Insulin
  Inhaled insulin with dose adjusted according to premeal blood glucose

Study Arms

• Active Comparator: Subcutaneous Insulin
  Intervention: Drug: Subcutaneous Insulin
• Experimental: Inhaled Insulin
  Intervention: Drug: Inhaled Insulin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 7, 2009): 582
• Original Enrollment (submitted: August 26, 2005): 600
• Actual Study Completion Date: December 2008
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Type 1 diabetes mellitus

Exclusion Criteria:

• severe asthma or COPD
• smoking
• brittle diabetes

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Canada, Mexico, United States
• Removed Location Countries: Venezuela

Administrative Information

• NCT Number: NCT00137046
• Other Study ID Numbers: A2171022
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2009