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

February 3, 2010 updated by: Pfizer

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Enrollment (Actual)

582

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentina, C1120 AAF
        • Pfizer Investigational Site
      • Capital Federal, Buenos Aires, Argentina, C1181 ACH
        • Pfizer Investigational Site
      • Capital Federal, Buenos Aires, Argentina, C1405 DCS
        • Pfizer Investigational Site
      • Capital Federal, Buenos Aires, Argentina, C1427 AQR
        • Pfizer Investigational Site
  • Brazil
    • MG
      • Belo Horizonte, MG, Brazil, 30150-221
        • Pfizer Investigational Site
    • PR
      • Curitiba, PR, Brazil, 80420-011
        • Pfizer Investigational Site
    • RS
      • Porto Alegre, RS, Brazil, 90035-170
        • Pfizer Investigational Site
      • Porto Alegre, RS, Brazil, 90035-903
        • Pfizer Investigational Site
    • SP
      • Campinas, SP, Brazil, 13083-900
        • Pfizer Investigational Site
      • Sao Paulo, SP, Brazil, 01244-030
        • Pfizer Investigational Site
      • Sao Paulo, SP, Brazil, 04231-030
        • Pfizer Investigational Site
      • São Paulo, SP, Brazil, 04020-041
        • Pfizer Investigational Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • Pfizer Investigational Site
      • Calgary, Alberta, Canada, T3B 0M3
        • Pfizer Investigational Site
      • Edmonton, Alberta, Canada, T5J 3N4
        • Pfizer Investigational Site
      • Edmonton, Alberta, Canada, T6G 2C8
        • Pfizer Investigational Site
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 1J8
        • Pfizer Investigational Site
    • Manitoba
      • Winnepeg, Manitoba, Canada, R3A 1R9
        • Pfizer Investigational Site
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • Pfizer Investigational Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Pfizer Investigational Site
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Pfizer Investigational Site
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Pfizer Investigational Site
      • London, Ontario, Canada, N6A 4V2
        • Pfizer Investigational Site
      • Mississauga, Ontario, Canada, L5M 2V8
        • Pfizer Investigational Site
      • Oakville, Ontario, Canada, L6H 3P1
        • Pfizer Investigational Site
      • Ottawa, Ontario, Canada, K1H 1A2
        • Pfizer Investigational Site
      • Thornhill, Ontario, Canada, L4J 8L7
        • Pfizer Investigational Site
      • Toronto, Ontario, Canada, M4R 2G4
        • Pfizer Investigational Site
    • Quebec
      • Laval, Quebec, Canada, H7T 2P5
        • Pfizer Investigational Site
      • Montreal, Quebec, Canada, H3A 1A1
        • Pfizer Investigational Site
      • Montreal, Quebec, Canada, H1T 2M4
        • Pfizer Investigational Site
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Pfizer Investigational Site
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Pfizer Investigational Site
  • Mexico
    • Col Las Americas
      • Mexico Df, Col Las Americas, Mexico, 01120
        • Pfizer Investigational Site
    • DF
      • Mexico, DF, Mexico, 14000
        • Pfizer Investigational Site
      • Mexico, DF, Mexico, 02990
        • Pfizer Investigational Site
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64060
        • Pfizer Investigational Site
  • United States
    • California
      • Fullerton, California, United States, 92835
        • Pfizer Investigational Site
      • Long Beach, California, United States, 90806
        • Pfizer Investigational Site
      • Sacramento, California, United States, 95816
        • Pfizer Investigational Site
      • San Diego, California, United States, 92103
        • Pfizer Investigational Site
      • Santa Barbara, California, United States, 93105
        • Pfizer Investigational Site
      • Santa Rosa, California, United States, 95405
        • Pfizer Investigational Site
      • Tustin, California, United States, 92780
        • Pfizer Investigational Site
      • Walnut Creek, California, United States, 94598
        • Pfizer Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80220
        • Pfizer Investigational Site
      • Longmont, Colorado, United States, 80501
        • Pfizer Investigational Site
    • Connecticut
      • Hamden, Connecticut, United States, 06518
        • Pfizer Investigational Site
      • Madison, Connecticut, United States, 06443
        • Pfizer Investigational Site
    • Delaware
      • Newark, Delaware, United States, 19713
        • Pfizer Investigational Site
    • Florida
      • Coral Gables, Florida, United States, 33134
        • Pfizer Investigational Site
      • Hollywood, Florida, United States, 33021
        • Pfizer Investigational Site
      • Miami, Florida, United States, 33136
        • Pfizer Investigational Site
      • Tallahassee, Florida, United States, 32308
        • Pfizer Investigational Site
      • West Palm Beach, Florida, United States, 33401
        • Pfizer Investigational Site
      • Winter Park, Florida, United States, 32789
        • Pfizer Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60610
        • Pfizer Investigational Site
      • Chicago, Illinois, United States, 60602
        • Pfizer Investigational Site
      • Wilmette, Illinois, United States, 60091
        • Pfizer Investigational Site
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Pfizer Investigational Site
    • Missouri
      • St. Louis, Missouri, United States, 63141
        • Pfizer Investigational Site
    • Montana
      • Butte, Montana, United States, 59701
        • Pfizer Investigational Site
    • New York
      • New Hyde Park, New York, United States, 11042
        • Pfizer Investigational Site
    • North Carolina
      • Durham, North Carolina, United States, 27713
        • Pfizer Investigational Site
    • Oregon
      • Portland, Oregon, United States, 97210
        • Pfizer Investigational Site
    • Pennsylvania
      • Lansdale, Pennsylvania, United States, 19446
        • Pfizer Investigational Site
    • Texas
      • Dallas, Texas, United States, 75230
        • Pfizer Investigational Site
      • Dallas, Texas, United States, 75246
        • Pfizer Investigational Site
      • San Antonio, Texas, United States, 78229
        • Pfizer Investigational Site
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Pfizer Investigational Site
    • Virginia
      • Richmond, Virginia, United States, 23225
        • Pfizer Investigational Site
    • Washington
      • Renton, Washington, United States, 98057
        • Pfizer Investigational Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53209
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 1 diabetes mellitus

Exclusion Criteria:

  • severe asthma or COPD
  • smoking
  • brittle diabetes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Subcutaneous Insulin
Drug: Subcutaneous Insulin
Subcutaneous insulin with dose adjusted according to premeal blood glucose
Experimental: Inhaled Insulin
Drug: Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline through Extension Follow-up Month 3
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.
Month 3 through Extension Follow-up 3
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).
Baseline through Extension Follow-up Month 3
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.
Month 3 through Extension Follow-up Month 3
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).
Week -2 through Extension Follow-up Month 6 or end of study
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).
Week -2 through Extension Follow-up Month 6 or end of study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline through Extension Follow-up Month 3
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.
Month 1 through Extension Month 39
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.
Month 1 through Extension Month 39
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).
Baseline through Extension Follow-up Month 3
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.
Baseline through Extension Follow-up Month 3
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.
Month 3 through Extension Month 39
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.
Month 3 through Extension Month 39
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.
Month 3 through Extension Month 39
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.
Month 3 through Extension Month 39
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.
Week - 1
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.
Week 4 through ,Extension Follow-up Month 6 and every 6 months thereafter or end of study
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).
Week -4 through Month 24
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.
Week 0 and if indicated through Extension Follow up Month 3
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).
Week -3 through Extension Follow-up Month 6 or End of Study
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).
Week -3 through Extension Follow-up Month 6 or End of Study
Insulin Antibodies
Time Frame: Baseline through Extension Month 39
Median insulin antibodies at each visit measured in micro units per milliliter (microU/mL).
Baseline through Extension Month 39

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

August 26, 2005

First Submitted That Met QC Criteria

August 26, 2005

First Posted (Estimate)

August 29, 2005

Study Record Updates

Last Update Posted (Estimate)

February 18, 2010

Last Update Submitted That Met QC Criteria

February 3, 2010

Last Verified

December 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A2171022

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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