Efficacy and Safety of Inhaled Insulin Compared With Subcutaneous Human Insulin Therapy in Adults With Type 2 Diabetes

February 12, 2010 updated by: Pfizer

Efficacy and Safety of Exubera® (Inhaled Insulin) Compared With Subcutaneous Human Insulin Therapy in Adult Subjects With Type 2 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 inhaled insulin that is used by oral inhalation, to adult males and females with type 2 diabetes mellitus. The other name for this inhaled insulin is Exubera®.

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 A2171029 was terminated on June 9, 2008. Neither safety nor efficacy reasons were the cause of the study termination.

Study Type

Interventional

Enrollment (Actual)

635

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

  • Brazil
    • RS
      • Porto Alegre, RS, Brazil, 90035-170
        • Pfizer Investigational Site
    • SP
      • Sao Paulo, SP, Brazil, 01244-030
        • Pfizer Investigational Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5C7
        • Pfizer Investigational Site
      • Calgary, Alberta, Canada, T3B 0M3
        • Pfizer Investigational Site
      • Red Deer, Alberta, Canada, T4N 6V7
        • 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
      • London, Ontario, Canada, N6A 4V2
        • Pfizer Investigational Site
      • Ottawa, Ontario, Canada, K1H 1A2
        • Pfizer Investigational Site
      • Toronto, Ontario, Canada, M4N-3M5
        • Pfizer Investigational Site
      • Toronto, Ontario, Canada, M5G 1X5
        • 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
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Pfizer Investigational Site
  • Puerto Rico
      • Aguas Buenas, Puerto Rico, 00703
        • Pfizer Investigational Site
      • Anasco, Puerto Rico, 00610
        • Pfizer Investigational Site
      • Cabo Rojo, Puerto Rico, 00623
        • Pfizer Investigational Site
      • San Juan, Puerto Rico, 00909
        • Pfizer Investigational Site
      • San Juan, Puerto Rico, 00921
        • Pfizer Investigational Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Pfizer Investigational Site
      • Tucson, Arizona, United States, 85715
        • Pfizer Investigational Site
    • California
      • Fresno, California, United States, 93720
        • Pfizer Investigational Site
      • Greenbrae, California, United States, 94904
        • Pfizer Investigational Site
      • Los Angeles, California, United States, 90073
        • Pfizer Investigational Site
      • Sacramento, California, United States, 95816
        • Pfizer Investigational Site
      • San Diego, California, United States, 92108
        • Pfizer Investigational Site
      • San Diego, California, United States, 92103
        • Pfizer Investigational Site
      • San Luis Obispo, California, United States, 93401
        • 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, 80209
        • Pfizer Investigational Site
    • Connecticut
      • Hamden, Connecticut, United States, 06518
        • Pfizer Investigational Site
      • Madison, Connecticut, United States, 06443
        • Pfizer Investigational Site
      • New Britain, Connecticut, United States, 06050
        • Pfizer Investigational Site
      • Waterbury, Connecticut, United States, 06708
        • Pfizer Investigational Site
    • Florida
      • Chiefland, Florida, United States, 32626
        • Pfizer Investigational Site
      • Clearwater, Florida, United States, 33761
        • Pfizer Investigational Site
      • Fort Myers, Florida, United States, 33901
        • Pfizer Investigational Site
      • Hollywood, Florida, United States, 33021
        • Pfizer Investigational Site
      • Miami, Florida, United States, 33156
        • Pfizer Investigational Site
      • Ocala, Florida, United States, 34471
        • Pfizer Investigational Site
      • Palm Harbor, Florida, United States, 34684
        • Pfizer Investigational Site
      • Tallahassee, Florida, United States, 32308
        • Pfizer Investigational Site
      • West Palm Beach, Florida, United States, 33401
        • Pfizer Investigational Site
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Pfizer Investigational Site
      • Honolulu, Hawaii, United States, 96814
        • Pfizer Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Pfizer Investigational Site
      • Chicago, Illinois, United States, 60610
        • Pfizer Investigational Site
      • Chicago, Illinois, United States, 60602
        • Pfizer Investigational Site
      • Springfield, Illinois, United States, 62704
        • Pfizer Investigational Site
      • Wilmette, Illinois, United States, 60091
        • Pfizer Investigational Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Pfizer Investigational Site
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Pfizer Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Pfizer Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Pfizer Investigational Site
      • Bloomfield Hills, Michigan, United States, 48302
        • Pfizer Investigational Site
      • Plymouth, Michigan, United States, 48170
        • Pfizer Investigational Site
      • Royal Oak, Michigan, United States, 48073
        • Pfizer Investigational Site
      • Southfield, Michigan, United States, 48034
        • Pfizer Investigational Site
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Pfizer Investigational Site
      • St. Louis, Missouri, United States, 63141
        • Pfizer Investigational Site
    • Montana
      • Butte, Montana, United States, 59701
        • Pfizer Investigational Site
    • Nebraska
      • Lincoln, Nebraska, United States, 68521
        • Pfizer Investigational Site
    • Nevada
      • Henderson, Nevada, United States, 89014
        • Pfizer Investigational Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Pfizer Investigational Site
      • Albuquerque, New Mexico, United States, 87108
        • Pfizer Investigational Site
    • New York
      • Mineola, New York, United States, 11501
        • Pfizer Investigational Site
      • New Hyde Park, New York, United States, 11042
        • Pfizer Investigational Site
      • Rochester, New York, United States, 14609
        • Pfizer Investigational Site
    • North Carolina
      • Durham, North Carolina, United States, 27713
        • Pfizer Investigational Site
      • Winston-Salem, North Carolina, United States, 27103
        • Pfizer Investigational Site
    • Ohio
      • Mansfield, Ohio, United States, 44903
        • Pfizer Investigational Site
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
        • Pfizer Investigational Site
    • Rhode Island
      • Warwick, Rhode Island, United States, 02886
        • Pfizer Investigational Site
    • Texas
      • Beaumont, Texas, United States, 77701
        • Pfizer Investigational Site
      • Beaumont, Texas, United States, 77706
        • Pfizer Investigational Site
      • Corpus Christi, Texas, United States, 78412
        • Pfizer Investigational Site
      • Corpus Christi, Texas, United States, 78411
        • Pfizer Investigational Site
      • Dallas, Texas, United States, 75231
        • Pfizer Investigational Site
      • Dallas, Texas, United States, 75230
        • Pfizer Investigational Site
      • Dallas, Texas, United States, 75246
        • Pfizer Investigational Site
      • Houston, Texas, United States, 77079
        • Pfizer Investigational Site
      • Irving, Texas, United States, 75061
        • 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, 98055
        • 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

35 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 2 diabetes mellitus

Exclusion Criteria:

  • COPD
  • Asthma
  • Smoking Pregnancy

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
Experimental: Inhaled Insulin
Inhalable short-acting insulin
Drug: Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose
Other Names:
  • Exubera
Active Comparator: Subcutaneous insulin
Drug: Subcutaneous insulin
Subcutaneous 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 Month 3 in Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: Month 3 through extension Month 60
Change from Month 3: mean of (value of observed FEV1 [forced expiratory volume in the first second of forced exhalation] in liters [L] at treatment observation minus Month 3 value).
Month 3 through extension Month 60
Change From Baseline in FEV1
Time Frame: Baseline through extension follow up Month 3
Change from baseline: mean of (value of observed FEV1 [L] at treatment observation minus baseline value).
Baseline through extension follow up Month 3
Annual Rate of Change in FEV1
Time Frame: Week -2 through extension follow up Month 3 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 3 or end of study
Summary of ≥ 15 % Decliners in FEV1
Time Frame: Month 3 through extension follow up Month 3
Number of subjects with a post-baseline FEV1 decrease of ≥ 15 % [(baseline observed value - visit observed value)/(baseline observed value) * 100]; in the absence of an obvious intercurrrent illness, a repeat FEV1 was performed.
Month 3 through extension follow up Month 3
Annual Rate of Change in Carbon Monoxide Diffusion Capacity (DLco)
Time Frame: Week -2 through extension follow up Month 3 or end of study
Annual rate of change in DLco calculated as slope over time (visit) measured as milliliters per minute per millimeters of mercury per year (ml/min/mmHg/yr).
Week -2 through extension follow up Month 3 or end of study
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 observed DLco [milliliters per minute per millimeters of mercury (ml/min/mmHg)] at treatment observation minus baseline value).
Baseline through extension follow up Month 3
Summary of ≥ 20 % Decliners in DLco
Time Frame: Month 3 through extension follow up Month 3
Number of subjects with a post-baseline DLco decrease of ≥ 20 % [(baseline observed value - visit observed value)/(baseline observed value) * 100]; in the absence of an obvious intercurrrent illness, a repeat DLco was performed.
Month 3 through extension follow up Month 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Forced Vital Capacity (FVC)
Time Frame: Week -3 through extension follow up Month 3 or end of study
Forced Vital Capacity (FVC) measured in liters (L).
Week -3 through extension follow up Month 3 or end of study
Total Lung Capacity (TLC)
Time Frame: Baseline through extension follow up Month 3
Total Lung Capacity measured in liters (L).
Baseline through extension follow up Month 3
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Time Frame: Baseline through extension follow up Month 3
Change from baseline: mean of (value of observed HbA1c [%] at treatment observation minus baseline value).
Baseline through extension follow up Month 3
Change From Baseline in Fasting Plasma Glucose (FPG)
Time Frame: Baseline through extension follow up Month 3
Change from baseline: mean of (value of observed FPG [milligrams per deciliter (mg/dL)] at treatment observation minus baseline value).
Baseline through extension follow up Month 3
Change From Baseline in Body Weight
Time Frame: Baseline through extension follow up Month 3
Change from baseline: mean of (value of observed body weight [kilograms (kg)] at treatment observation minus baseline value).
Baseline through extension follow up Month 3
Total Daily Long-acting Insulin Dose (Unadjusted for Body Weight)
Time Frame: Month 3 through extension Month 36
Total daily long-acting insulin dose unadjusted for body weight. Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine.
Month 3 through extension Month 36
Total Daily Long-acting Insulin (Adjusted for Body Weight)
Time Frame: Month 3 through extension Month 36
Total daily dose of long-acting insulin adjusted for body weight (units per kilogram [kg]). Long-acting (units) insulin for inhaled insulin and subcutaneous treatment groups included NPH insulin, Ultralente®, and insulin glargine.
Month 3 through extension Month 36
Total Daily Short-acting Insulin Dose (Unadjusted for Body Weight)
Time Frame: Month 3 through extension Month 36
Total daily dose of short-acting insulin unadjusted for body weight. Short-acting insulin (milligrams [mg]) for the inhaled insulin treatment group was inhaled insulin; short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin.
Month 3 through extension Month 36
Total Daily Short-acting Insulin Dose (Adjusted for Body Weight)
Time Frame: Month 3 through extension Month 36
Total daily dose of short-acting insulin adjusted for body weight. Short-acting insulin (mg) for the inhaled insulin treatment group was inhaled insulin (mg divided by kg); short-acting insulin (units) for the subcutaneous insulin treatment group included insulin lispro, insulin aspart, and regular insulin (units divided by kg).
Month 3 through extension Month 36
Lipid Panel: Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein, and Triglycerides
Time Frame: Week -4 through Month 24
Lipid values for total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides measured as milligrams per deciliter (mg/dL).
Week -4 through Month 24
Hypoglycemic Event Rates
Time Frame: Month 1 through extension Month 36
Hypoglycemic event rate; hypoglycemic event identified by characteristic symptoms of hypoglycemia with no blood glucose (BG) check with prompt resolution with food intake, SC glucagon, or intravenous (IV) glucose; characteristic symptoms with BG of 59 mg/dL (3.2 mmol/L) or less with or without symptoms. Crude event rate = total events divided by subject months (elapsed number of months a subject was in the study at each time interval).
Month 1 through extension Month 36
Severe Hypoglycemic Event Rates
Time Frame: Month 1 through extension Month 36
Severe hypoglycemic event rate; all 3 criteria were met: subject unable to treat self, exhibited at least 1 neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty awakening, suspected seizure, loss of consciousness); BG measurement ≤49 mg/dL, or not measured but clinical manifestations reversed by oral carbohydrates, SC glucagon, or IV glucose. Crude event rate: total events divided by subject months multiplied by 100 ([total events/subject months]*100). Subjects months: elapsed number of months subject was in study in each time interval.
Month 1 through extension Month 36
Cough Questionnaire
Time Frame: Week 0 and if indicated through extension follow up Month 3
Clinician administered 6 question instrument to measure cough frequency (night, day), severity, timing in relation to short-acting insulin dosing, severity related to insulin dosing (SC or inhaled), and productivity of cough; range 0 (indicates no symptoms) to 4 (indicates severe symptoms). Questionnaire administered at Week 0 then if and only if, cough is 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
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 3 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 3 or end of study
High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Within Normal Limits
Time Frame: Baseline, M12, M24, Ext M6, Ext M18, Ext M36
Number of subjects with Yes or No responses (within normal limits at specified time points = Yes or not within normal limits at specified time points = No) at observation when HRCT of thorax was within normal limits at baseline.
Baseline, M12, M24, Ext M6, Ext M18, Ext M36
High Resolution Computerized Tomography (HRCT) Scan: Within Normal Limits (Yes or No) at Observation When Baseline HRCT Was Not Within Normal Limits
Time Frame: Baseline, M12, M24, Ext M6, Ext M18, Ext M36
Number of subjects with Yes or No responses (within normal limits at specified time points = Yes or not within normal limits at specified time points = No) at observation when HRCT of thorax was not within normal limits at baseline. "No" response at observation further categorized as no significant change (NSC), more abnormal (> Abn), or less abnormal (< Abn).
Baseline, M12, M24, Ext M6, Ext M18, Ext M36
Insulin Antibodies
Time Frame: Baseline through extension Month 36
Observed values for insulin antibodies measured as micro units per milliliter (microU/mL).
Baseline through extension Month 36

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.

General Publications

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

June 1, 2002

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

August 25, 2005

First Submitted That Met QC Criteria

August 25, 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 12, 2010

Last Verified

December 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A2171029

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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