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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE August 25, 2005
First Posted Date  ICMJE August 29, 2005
Results First Submitted Date  ICMJE December 10, 2009
Results First Posted Date  ICMJE January 18, 2010
Last Update Posted Date February 18, 2010
Study Start Date  ICMJE June 2002
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2009)
  • 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).
  • 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).
  • 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).
  • 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.
  • 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).
  • 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).
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 25, 2005)
The primary outcome is to assess the toleration and safety of inhaled insulin compared to subcutaneous insulin therapy and the effects if any on measures of pulmonary function.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2010)
  • 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).
  • Total Lung Capacity (TLC) [ Time Frame: Baseline through extension follow up Month 3 ]
    Total Lung Capacity measured in liters (L).
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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 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.
  • 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.
  • 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).
  • Insulin Antibodies [ Time Frame: Baseline through extension Month 36 ]
    Observed values for insulin antibodies measured as micro units per milliliter (microU/mL).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2005)
Secondary endpoints include: hbA1c, fasting plasma glucose, body weight, insulin dose, incidence and severity of 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  ICMJE Efficacy and Safety of Inhaled Insulin Compared With Subcutaneous Human Insulin Therapy in Adults With Type 2 Diabetes
Official Title  ICMJE 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
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus
Intervention  ICMJE
  • Drug: Inhaled Insulin
    Inhaled insulin with dose adjusted according to premeal blood glucose
    Other Name: Exubera
  • Drug: Subcutaneous insulin
    Subcutaneous insulin with dose adjusted according to premeal blood glucose
Study Arms  ICMJE
  • Experimental: Inhaled Insulin
    Inhalable short-acting insulin
    Intervention: Drug: Inhaled Insulin
  • Active Comparator: Subcutaneous insulin
    Intervention: Drug: Subcutaneous insulin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 8, 2009)
635
Original Enrollment  ICMJE
 (submitted: August 25, 2005)
600
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Type 2 diabetes mellitus

Exclusion Criteria:

  • COPD
  • Asthma
  • Smoking Pregnancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00136916
Other Study ID Numbers  ICMJE A2171029
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Director, Clinical Trial Disclosure Group, Pfizer, Inc.
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP