A Clinical Trial Comparing the Efficacy and Safety of Exubera® and Lantus®

A Six Month, Open-Label Outpatient, Randomized Parallel Group Trial Assessing The Impact Of Dry Powder Inhaled Insulin (Exubera®) On Glycemic Control Compared To Insulin Glargine (Lantus®) In Patients With Type 2 Diabetes Mellitus Who Are Poorly Controlled On A Combination Of Two Or More Oral Agents

To compare efficacy and safety of Exubera® vs Lantus® in patients with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin Glargine (Lantus®); Drug: Inhaled Human Insulin (Exubera®)

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Bornem, Belgium, 2800
    • Pfizer Investigational Site
  • Brussels, Belgium, 1070
    • Pfizer Investigational Site
  • Genk, Belgium, 3600
    • Pfizer Investigational Site
  • Liège 1, Belgium, 4000
    • Pfizer Investigational Site
• Finland
  • Kuopio, Finland, 70210
    • Pfizer Investigational Site
  • Lahti, Finland, 15110
    • Pfizer Investigational Site
  • Oulu, Finland, 90100
    • Pfizer Investigational Site
• France
  • Besancon, France, 25030
    • Pfizer Investigational Site
  • Corbeil Essonnes Cedex, France, 91106
    • Pfizer Investigational Site
  • LA Rochelle CEDEX, France, 17019
    • Pfizer Investigational Site
  • Marseille Cedex 5, France, 13385
    • Pfizer Investigational Site
  • Paris Cedex 10, France, 75475
    • Pfizer Investigational Site
  • Valenciennes Cedex 1, France, 59300
    • Pfizer Investigational Site
• Germany
  • Altenburg, Germany, 04600
    • Pfizer Investigational Site
  • Eisenach, Germany, 99817
    • Pfizer Investigational Site
  • Hamburg, Germany, 20253
    • Pfizer Investigational Site
  • Hohenmoelsen, Germany, 06679
    • Pfizer Investigational Site
  • Leipzig, Germany, 04103
    • Pfizer Investigational Site
  • Neuss, Germany, 41460
    • Pfizer Investigational Site
  • Riesa, Germany, 01587
    • Pfizer Investigational Site
  • Wangen / Allgaeu, Germany, 88239
    • Pfizer Investigational Site
• Netherlands
  • Den Bosch, Netherlands, 5233 VG
    • Pfizer Investigational Site
  • Den Haag, Netherlands, 2512 VA
    • Pfizer Investigational Site
  • Eindhoven, Netherlands, 5631 BM
    • Pfizer Investigational Site
  • Nijmegen, Netherlands, 6525 EC
    • Pfizer Investigational Site
  • Venlo, Netherlands, 5912 BL
    • Pfizer Investigational Site
• Norway
  • Bergen, Norway, 5012
    • Pfizer Investigational Site
  • Jessheim, Norway, 2050
    • Pfizer Investigational Site
  • Lysaker, Norway
    • Pfizer Investigational Site
  • Skedsmokorset, Norway, N-2020
    • Pfizer Investigational Site
  • Buskerud
    • Honefoss, Buskerud, Norway, 3505
      • Pfizer Investigational Site
• Poland
  • Lask, Poland, 98-100
    • Pfizer Investigational Site
  • Lodz, Poland, 93-338
    • Pfizer Investigational Site
  • Lodz, Poland, 90-030
    • Pfizer Investigational Site
  • Lublin, Poland, 20-536
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-097
    • Pfizer Investigational Site
• Spain
  • A Coruña, Spain, 15006
    • Pfizer Investigational Site
  • Huelva, Spain, 21080
    • Pfizer Investigational Site
  • Malaga, Spain, 29006
    • Pfizer Investigational Site
  • Valencia, Spain, 46015
    • Pfizer Investigational Site
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07014
      • Pfizer Investigational Site
  • Mallorca
    • Inca, Mallorca, Spain, 07300
      • Pfizer Investigational Site
  • Santa Cruz de Tenerife
    • La Laguna, Santa Cruz de Tenerife, Spain, 38320
      • Pfizer Investigational Site
  • Valencia
    • Alzira, Valencia, Spain, 46600
      • Pfizer Investigational Site
• Sweden
  • Boras, Sweden, 501 82
    • Pfizer Investigational Site
  • Eksjo, Sweden, 575 36
    • Pfizer Investigational Site
  • Goteborg, Sweden, 412 55
    • Pfizer Investigational Site
  • Goteborg, Sweden, 41665
    • Pfizer Investigational Site
  • Harnosand, Sweden, 871 82
    • Pfizer Investigational Site
  • Helsingborg, Sweden, 25220
    • Pfizer Investigational Site
  • Järfälla, Sweden, 177 31
    • Pfizer Investigational Site
  • Kristianstad, Sweden, 291 54
    • Pfizer Investigational Site
  • Linkoping, Sweden, 581 85
    • Pfizer Investigational Site
  • Lulea, Sweden, 972 33
    • Pfizer Investigational Site
  • Malmo, Sweden, 211 52
    • Pfizer Investigational Site
  • Motala, Sweden, 591 85
    • Pfizer Investigational Site
  • Stockholm, Sweden, 118 83
    • Pfizer Investigational Site
  • Uddevalla, Sweden, 451 50
    • Pfizer Investigational Site
  • Umea, Sweden, 901 85
    • Pfizer Investigational Site
  • Vaxjo, Sweden, 351 85
    • Pfizer Investigational Site
• Switzerland
  • Bruderholz, Switzerland, 4101
    • Pfizer Investigational Site
  • St. Gallen, Switzerland, CH-9007
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diabetes Mellitus, Type 2 on oral agents
• Age > 30 years

Exclusion Criteria:

• Severe Asthma, severe Chronic Obstructive Pulmonary Disease
• 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: Insulin Glargine (Lantus®)	Drug: Insulin Glargine (Lantus®); Patient will be randomized to Lantus® while remaining on pre-study oral hypoglycemic agents.
Active Comparator: Inhaled Human Insulin (Exubera®)	Drug: Inhaled Human Insulin (Exubera®); Patient will be randomized inhaled insulin while remaining on pre-study oral hypoglycemic agents.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26	Change (measured as percent): HbA1c at observation minus HbA1c at baseline. Primary objective to demonstrate non-inferiority of inhaled insulin compared to insulin glargine for glycemic control after 26 weeks of treatment not attainable due to early termination of study; analyses were descriptive and graphical.	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c Prior to Week 26	Change (measured as percent) from baseline calculated as HbA1c at observation minus HbA1c at baseline.	Baseline, Week 2, Week 4, Week 8, Week 12, and Week 18
Number of Subjects With HbA1c < 6.5 %	Number of subjects with glycemic control HbA1c measurement of < 6.5 % at observation.	Week 26
Number of Subjects With HbA1c < 7.0 %	Number of subjects with glycemic control HbA1c measurement of < 7.0 % at observation.	Week 26
Number of Subjects With HbA1c < 8.0 %	Number of subjects with glycemic control HbA1c measurement of < 8.0 % at observation.	Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) Level	FPG measured as milligrams/deciliter (mg/dl). Change from baseline calculated as FPG at observation minus FPG at baseline.	Baseline, Week 26
Analysis of Home Blood Glucose Monitoring (HBGM) (7 & 8 Point)	Blood glucose (BG) self-monitored by subject at home; measured at least once between Visits 2, 3 and between Visits 8, 9 (8-point: fasting, pre-meal, post-meal, bedtime, 2:00 am); between each visit: Visit 3 to 8 (7-point: fasting, post-meal, pre-lunch, pre-dinner, bedtime). Post-meal: 2-hour period after breakfast, lunch, dinner. Change: average overall absolute, pre-meal, and post-meal blood glucose = HBGM at observation minus HBGM at baseline; pre-meal to post-meal blood glucose = HBGM at post-meal minus HBGM at pre-meal.	Baseline, Week 26
Number of Subjects With Hypoglycemic Events by Severity	Number of subjects with hypoglycemic events by severity. Severe hypoglycemia: subject unable to treat self; exhibits a neurological symptom; and blood glucose <=2.72 mmol/L or blood glucose not measured but symptoms reversed with food intake, SC glucagon, or intravenous glucose. If all 3 criteria not met, hypoglycemia defined as mild or moderate.	Week 26
Number of Events of Nocturnal Hypoglycemia	Number of events of nocturnal hypoglycemia, incidence: midnight to 6:00 am. Hypoglycemia: characteristic symptoms of hypoglycemia with no blood glucose check; resolved with food intake, SC glucagon, or intravenous (IV) glucose; or symptoms with glucose <3.27 mmol/L (59 mg/dL); or any glucose measurement <=2.72 mmol/L (49 mg/dl). Severity of nocturnal glycemia not summarized.	Week 26
Change From Baseline in Body Weight	Change from baseline calculated as body weight at observation minus body weight at baseline.	Baseline, Week 26
Change From Baseline in Body Mass Index (BMI)	BMI measured as kilograms per meter squared (kg/m2). Change calculated as BMI at observation minus BMI at baseline.	Baseline, Week 26
Number of Subjects Discontinued Due to Insufficient Clinical Response	Number of subjects discontinued due to signs and symptoms of persistent hyperglycemia or HbA1c > 12.0 % or frequent and unexplained severe hypoglycemic events (> 3 events per month for 2 or more months); subject's HbA1c not < = 7 % at Week 12.	Week 26
Change From Baseline in Treatment Satisfaction, Quality of Life, and Mental Health	Subject reported outcomes for Diabetes Treatment Satisfaction Questionnaire-Status (DTSQs), DTSQ-change, Patient Satisfaction with Insulin Therapy-16 item, Mental Health Inventory-17 item, and Euro Quality of life 5-Dimensions (EuroQol 5-D) Questionnaire not summarized due to cancellation of Exubera® program.	Week 26
Continuous Glucose Monitoring System (CGMS) 24-hour Glucose Profile in a Subset of Patients	The mean of the 24-hour mean and the mean of the 24-hour standard deviation (SD) (variability around the average glucose concentration) calculated on glucose values (mg/dl) collected during inpatient evaluation of glycemic stability. Interstitial glucose assessed at 5 minute intervals starting pre-supper on Day 1 of evaluation; ending on Day 3 pre-breakfast. Analysis is on data generated between 6:00 am on Day 2 and 6:00 am on Day 3.	Baseline, Week 26
Change From Baseline in Cardiovascular (CV) Biomarkers - High Sensitive C-reactive Protein (Hs-CRP)	Change from baseline in CV biomarker hs-CRP (milligrams per deciliter [mg/dl]) calculated as hs-CRP at observation minus hs-CRP at baseline.	Baseline, Week 26
Change From Baseline in CV Biomarkers - Interleukin 6 (IL-6)	Change from baseline in IL-6 (picograms per milliliter [pg/ml]) calculated as IL-6 at observation minus IL-6 at baseline.	Baseline, Week 26
Change From Baseline in CV Biomarkers - Thrombin-antithrombin Complexes (Tat-complexes)	Change from baseline in tat-complexes (nanograms per milliliter [ng/ml]) calculated as tat-complexes at observation minus tat-complexes at baseline.	Baseline, Week 26
Change From Baseline in CV Biomarkers - Soluble Tissue Factor (STF)	Change from baseline in soluble tissue factor (pg/ml) calculated as STF at observation minus STF at baseline.	Baseline, Week 26
Change From Baseline in Urinary Free 8-iso Prostaglandin F2-alpha (α) in a Subset of Subjects	Urinary free 8-iso prostaglandin F2-alpha (α): compare glucose fluctuations and activation of oxidative stress as assessed by urinary isoprostanes in a subset of subjects randomized to either Exubera® or subcutaneous insulin glargine. The substudy was offered to all subjects. Data not summarized due to cancellation of Exubera® program.	Baseline, Week 26

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: October 19, 2006
• First Submitted That Met QC Criteria: October 19, 2006
• First Posted (Estimate): October 23, 2006

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: June 30, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: type 2 diabetes, insulin, glycemic control
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: A2171084