A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics With COPD

Efficacy and Safety of Inhaled Human Insulin (Exubera) Compared With Subcutaneous Human Insulin in the Therapy of Adult Subjects With Type 1 or Type 2 Diabetes Mellitus and Chronic Obstructive Pulmonary Disease: A One-Year, Multicenter, Randomized, Outpatient, Open-Label, Parallel-Group Comparative Trial

A One Year Clinical Trial Assessing the Usefulness and Safety of Inhaled Insulin in Diabetics with Chronic Obstructive Pulmonary Disease.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus; Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Subcutaneous Insulin; Drug: Inhaled Insulin

Detailed Description

Pfizer announced in October 2007 that it would stop marketing Exubera. At that time recruitment for study A2171030 was placed on hold. 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 A2171030 was terminated on June 17, 2008. Neither safety nor efficacy reasons were the cause of the study termination.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-170
      • Pfizer Investigational Site
  • SP
    • Campinas, SP, Brazil, 13083-900
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 01244-030
      • Pfizer Investigational Site
    • São Paulo, SP, Brazil, 04231-030
      • Pfizer Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5J 3N4
      • Pfizer Investigational Site
    • Red Deer, Alberta, Canada, T4N 6V7
      • Pfizer Investigational Site
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • Pfizer Investigational Site
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Pfizer Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Pfizer Investigational Site
• Costa Rica
  • San Jose, Costa Rica
    • Pfizer Investigational Site
• Germany
  • Neuss, Germany, 41460
    • Pfizer Investigational Site
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Pfizer Investigational Site
    • Peoria, Arizona, United States, 85381
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85004
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85006
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85016
      • Pfizer Investigational Site
    • Tucson, Arizona, United States, 85715
      • Pfizer Investigational Site
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Pfizer Investigational Site
    • Searcy, Arkansas, United States, 72143
      • Pfizer Investigational Site
  • California
    • Berkeley, California, United States, 94705
      • Pfizer Investigational Site
    • Fresno, California, United States, 93720
      • Pfizer Investigational Site
    • Greenbrae, California, United States, 94904
      • Pfizer Investigational Site
    • Huntington Beach, California, United States, 92648
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90073
      • Pfizer Investigational Site
    • Riverside, California, United States, 92506
      • Pfizer Investigational Site
    • Tustin, California, United States, 92780
      • Pfizer Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Pfizer Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Pfizer Investigational Site
  • Florida
    • Chiefland, Florida, United States, 32626
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33756
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33765
      • Pfizer Investigational Site
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site
    • Gainesville, Florida, United States, 32608
      • Pfizer Investigational Site
    • Lake City, Florida, United States, 32025
      • Pfizer Investigational Site
    • Melbourne, Florida, United States, 32901
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33144
      • Pfizer Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Pfizer Investigational Site
    • Winter Park, Florida, United States, 32789
      • Pfizer Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Pfizer Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pfizer Investigational Site
    • Honululu, Hawaii, United States, 96814
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Pfizer Investigational Site
    • Normal, Illinois, United States, 61761
      • Pfizer Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47713-1227
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46250
      • Pfizer Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Pfizer Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Pfizer Investigational Site
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Pfizer Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • Pfizer Investigational Site
    • Springfield, Massachusetts, United States, 01107
      • Pfizer Investigational Site
    • Waltham, Massachusetts, United States, 02453
      • Pfizer Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64106
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Pfizer Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89015
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89103
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89128
      • Pfizer Investigational Site
  • New York
    • Albany, New York, United States, 12205
      • Pfizer Investigational Site
    • Albany, New York, United States, 12206
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45242
      • Pfizer Investigational Site
    • Toledo, Ohio, United States, 43608
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Pfizer Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Pfizer Investigational Site
    • Portland, Oregon, United States, 97219
      • Pfizer Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • Pfizer Investigational Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Pfizer Investigational Site
    • Spartanburg, South Carolina, United States, 29307
      • Pfizer Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Pfizer Investigational Site
  • Texas
    • Beaumont, Texas, United States, 77701
      • Pfizer Investigational Site
    • Beaumont, Texas, United States, 77706
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75231
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78237
      • Pfizer Investigational Site
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Pfizer Investigational Site
    • Fredericksburg, Virginia, United States, 22408
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23225
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23229
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23235
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23249
      • Pfizer Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Pfizer Investigational Site
    • Spokane, Washington, United States, 99204
      • Pfizer Investigational Site
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Pfizer Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diabetes Mellitus (Type 1 or Type 2) currently controlled with injected insulin
• Prior smokers with a fixed airflow obstruction at screening (FEV1/FVC < 70%) and FEV1 < 80% predicted and/or a history of chronic productive cough.

Exclusion Criteria:

• Poorly controlled, unstable or steroid-dependent COPD, insulin pump therapy, active smoking

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subcutaneous Insulin	Drug: Subcutaneous Insulin; Subcutaneous short-acting insulin with dose adjusted according to premeal blood glucose plus oral antidiabetic agent(s) and/or either once or twice daily doses of either Ultralente or neutral protamine hagedorn (NPH) insulin, or a single bedtime dose of insulin glargine.
Experimental: Inhaled Insulin	Drug: Inhaled Insulin; Inhaled insulin with dose adjusted according to premeal blood glucose plus oral antidiabetic agent(s) and/or either once or twice daily doses of either Ultralente or NPH insulin, or a single bedtime dose of insulin glargine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	FEV1 was measured in liters (L) 30 minutes following the administration of ipratropium. Change from baseline: mean of (value of observed FEV1 (L) at treatment duration minus baseline value).	Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52
Change From Baseline in Post-Bronchodilator Carbon Monoxide Diffusion Capacity (DLco)	DLco measured in milliters/minutes/millimeters of mercury (mL/min/mmHg) 30 minutes following the administration of ipratropium. Change from baseline: mean of (value of observed DLco (mL/min/mmHg) at treatment duration minus baseline value).	Baseline, Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Full Pulmonary Function Tests (PFTs) (Spirometry, Pre-Ipratropium and Pre-Insulin PFTs)	Full PFTs included spirometry pre- and 30-minutes post-ipratropium and were completed between the hours of 6 AM and 10 AM with subjects in the fasting state. Full PFT data were collected, but not analyzed.	Duration of the study
Full PFTs (DLco, Pre-Ipratropium and Pre- Insulin PFTs)	Full PFTs included DLco pre- and 30-minutes post-ipratropium and were completed between the hours of 6 AM and 10 AM with subjects in the fasting state. Full PFT data were collected, but not analyzed.	Duration of the study
Other PFTs (Besides FEV1 and DLco)	Other PFTs (besides FEV1 and DLco) were measured 30 minutes following the administration of ipratropium. Other PFTs included forced vital capacity (FVC), peak expiratory flow rate (maximal forced expiratory flow) (PEFR[FEFmax]), and forced expiratory flow from 25% to 75% of vital capacity (FEF25%-75%). Other PFT data were collected, but not analyzed.	Duration of the study
Bronchodilator Responsiveness as Determined by the Change in FEV1	Responsiveness was the percent change from the FEV1 value before bronchodilator use to the FEV1 value 30 minutes after bronchodilator use, operationally defined as [(post-bronchodilator FEV1 minus pre-bronchodilator FEV1 divided by pre-bronchodilator FEV1] multiplied by 100.	Weeks 1, 2, 3, 4, 6, 12, 18, 26, 39, 52
Insulin Dose Responsiveness for FEV1	FEV1 dose responsiveness 10 and 60 minutes after insulin. FEV1 dose-responsiveness to insulin (defined as the difference between the FEV1 value following a dose of insulin and FEV1 value before a dose of insulin, operationally defined as the post-dose FEV1 value minus pre-dose FEV1 value).	Baseline, Week 9, Week 51
Insulin Dose Responsiveness for DLco	DLco dose responsivness 10 and 60 minutes after insulin. DLco dose-responsiveness to insulin (defined as the difference between the DLco value following a dose of insulin and DLco value before a dose of insulin, operationally defined as the post-dose DLco value minus pre-dose DLco value).	Baseline, Week 9, Week 51
Methacholine PC20	Methacholine challenge testing was conducted at selected sites at visits which did not occur at other sites (Weeks -2.9, -0.9, 11, 50 and 52+5). Methacholine challenge was not analyzed as there was only 1 test performed, which was a baseline test, and no methacholine tests performed in subjects using inhaled insulin.	Duration of the study
Mean Weekly Number of Puffs of Short-Acting Bronchodilator Used	All subjects used diary cards to record their daily use of short-acting bronchodilators. Subjects recorded the sum of their short-acting bronchodilator use (puffs of albuterol plus ipratropium plus Combivent®, as applicable) daily, immediately upon arising, and again in the evening or before bed. Mean weekly number of puffs of short-acting bronchodilator used data were collected, but not analyzed.	Duration of the study
Incidence of Non-Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	Non-severe COPD exacerbation = additional therapy (systemic corticosteroids, antibiotics, oxygen) needed for worsening respiratory symptoms and/or lung function, not needing hospitalization > 24 hours. Crude event rate = total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.	0 to 1 week to > 9 months
Incidence of Severe COPD Exacerbations	Severe COPD exacerbation = a COPD-related hospitalization > 24 hours. Crude event rate = total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.	0 to 1 week to > 9 months
Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) Questionnaires	The BDI and TDI measured or quantitated the severity of breathlessness (shortness of breath) in symptomatic subjects. BDI and TDI data were collected, but not analyzed.	Duration of the study
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	Change from baseline: mean of (value of observed HbA1c at treatment duration minus baseline value).	Baseline, Weeks 6, 12, 26, 39, and 52
Change From Baseline in Fasting Plasma Glucose	Change from baseline: mean of (value of observed fasting plasma glucose in milligrams/deciliters (mg/dL) at treatment duration minus baseline value).	Baseline, Weeks 6, 12, 26, 39, 52
Change From Baseline in Body Weight	Change from baseline: mean of (value of observed body weight in kilograms (kg) at treatment duration minus baseline value).	Baseline, Weeks 1, 2, 3, 4, 6, 9, 11, 12, 18, 26, 39, 50, 51, 52
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Unadjusted for Body Weight)	Intermediate-/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups.	Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Mean Total Daily Short-Acting Insulin Dose (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.	Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Mean Total Daily Intermediate-/Long-Acting Insulin Dose (Adjusted for Body Weight)	Intermediate/long-acting insulin included Insulin NPH, Ultralente, and Insulin Glargine for both groups. Dose was adjusted for body weight (units divided by kg).	Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Mean Total Daily Short-Acting Insulin Dose (Adjusted 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. Dose was adjusted for body weight (mg divided by kg or units divided by kg).	Weeks 1, 2, 3, 4, 6, 9, 12, 18, 26, 39, 52
Lipids	Lipids collected: Total cholesterol, high-density lipoprotein, low-density lipoptrotein, and triglycerides. Lipids data were collected, but not analyzed.	Duration of the study
Hypoglycemic Event Rates	A hypoglycemic event was identified by characteristic symptoms; blood glucose levels at 59 mg/dL (3.2 mmol/L) or less with a glucose check; or any glucose measurement 49 mg/dL (2.7 mmol/L) or less, with or without symptoms. Crude event rate=total events divided by subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.	0 to1 month to > 11 months
Severe Hypoglcyemic Event Rates	An event was severe if the subject was unable to treat him/herself; had at least 1 neurological symptom; or blood glucose of < = 49 mg/dL or the blood glucose was not measured, but the clinical manifestations were reversed by oral carbohydrates, subcutaneous glucagon, or intravenous glucose. Crude event rate=total events/100 subject-months. Subject-months=elapsed number of months a subject was in the study in each time interval.	0 to 1 month to > 11 months

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: August 26, 2005
• First Submitted That Met QC Criteria: August 26, 2005
• First Posted (Estimate): August 30, 2005

Study Record Updates

• Last Update Posted (Estimate): February 2, 2010
• Last Update Submitted That Met QC Criteria: January 25, 2010
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Respiratory Tract Diseases; Endocrine System Diseases; Diabetes Mellitus; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: A2171030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No