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

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ClinicalTrials.gov Identifier: NCT00136916
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : August 29, 2005
Results First Posted : January 18, 2010
Last Update Posted : February 18, 2010
Sponsor:
Information provided by:
Pfizer

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus Drug: Inhaled Insulin Drug: Subcutaneous insulin Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 635 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2002
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Inhaled Insulin
Inhalable short-acting insulin
 Drug: Inhaled Insulin
Inhaled insulin with dose adjusted according to premeal blood glucose
Other Name: Exubera
Active Comparator: Subcutaneous insulin Drug: Subcutaneous insulin
Subcutaneous insulin with dose adjusted according to premeal blood glucose


Outcome Measures
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Primary Outcome Measures :
  1. 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).

  2. 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).

  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).

  4. 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.

  5. 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).

  6. 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).

  7. 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.


Secondary Outcome Measures :
  1. 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).

  2. Total Lung Capacity (TLC) [ Time Frame: Baseline through extension follow up Month 3 ]
    Total Lung Capacity measured in liters (L).

  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).

  4. 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).

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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).

  10. 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).

  11. 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).

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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).

  18. Insulin Antibodies [ Time Frame: Baseline through extension Month 36 ]
    Observed values for insulin antibodies measured as micro units per milliliter (microU/mL).


Eligibility Criteria
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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus

Exclusion Criteria:

  • COPD
  • Asthma
  • Smoking Pregnancy
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00136916


Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00136916    
Other Study ID Numbers: A2171029
First Posted: August 29, 2005    Key Record Dates
Results First Posted: January 18, 2010
Last Update Posted: February 18, 2010
Last Verified: December 2009
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs