Clinical trial NCT01196104: Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Inhalation Insulin (TI) Inhalation Powder Using the Gen2 Inhaler
Official title: A Phase 3b, Multicenter, Open-label, Randomized, Forced-titration Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Insulin Inhalation Powder, Using the Gen2 Inhaler, in Combination With Insulin Glargine Versus Insulin Aspart in Combination With Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Over a 16-week Treatment Period
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Mannkind Corporation
Sponsor class: INDUSTRY
First posted: 2010-09-08
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, randomized, forced-titration clinical trial evaluating the efficacy and safety of Technosphere Insulin (TI) Inhalation Powder in combination with insulin glargine versus insulin aspart in combination with insulin glargine in subjects with type 2 diabetes.

Detailed description: Phase 3 clinical trial is designed to examine the efficacy and safety of inhaled prandial TI Inhalation Powder in combination with basal insulin verses insulin aspart in combination with basal insulin in subjects with type 2 diabetes who are suboptimally controlled with their current insulin regimens.This trial will employ a variety of methods to intensively manage these subjects.

Eligibility criteria: Inclusion Criteria:

* Men and women ≥ 18 and ≤ 80 years of age
* Clinical diagnosis of type 2 diabetes mellitus for more than 12 months
* Body mass index (BMI) ≤ 45 kg/m2
* Glycated Hemoglobin (HbA1c) \> 6.5% and ≤ 10.0%
* Treatment with 1 to 3 Oral Antidiabetic Drugs (OADs) and basal insulin for a minimum of 3 months before screening. Doses of OADs must have been stable for 3 months before study entry
* Nonsmokers (includes cigarettes, cigars, pipes, and chewing tobacco) for the preceding ≥ 6 months
* Office spirometry at the investigator site

  * Forced expiratory volume in 1 second (FEV1) ≥ 65% Third National Health and Nutrition Examination Survey (NHANES III) predicted
  * Forced vital capacity (FVC) ≥ 65% NHANES III predicted
  * Forced expiratory volume in 1 second as a percentage of forced vital capacity (FEV1/FVC) ≥ lower limit of normal (LLN)

Exclusion criteria:

* Current or prior treatment with prandial or PreMix (70/30) insulin
* History of insulin pump use within 6 weeks of Visit 1
* Treatment with Glucagon-like Peptide (GLP-1) analog drugs within the preceding 12 weeks of Visit 1
* History of chronic obstructive pulmonary disease (COPD), asthma, or any other clinically important pulmonary disease (eg, pulmonary fibrosis)
* Any clinically significant radiological findings on screening chest x-ray
* Use of medications for asthma, COPD, or any other chronic respiratory conditions
* Evidence of serious complications of diabetes (eg, symptomatic autonomic neuropathy)
* Significant cardiovascular dysfunction or history within 3 months of Visit 1 (eg, congestive heart failure \[New York Heart Association {NYHA} Class III or IV\])
* Serious arrhythmia, myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks, or any cerebrovascular accident
* History of pulmonary embolism or deep venous thrombosis in the 12 months before Screening (Visit 1)

Primary outcomes:
measure: Change in HbA1c (%) From Baseline to Week 16
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: To Evaluate the Effect of Each Treatment on HbA1c
timeFrame: Change from baseline to 16 weeks
measure: Comparison of Fasting Plasma Glucose (FPG) Levels at Randomization and Throughout the Study
timeFrame: Change from baseline to 16 weeks
measure: Comparison of Post-prandial Glucose (PPG) Levels at Randomization and Throughout the Study
timeFrame: Change from baseline to 16 weeks
measure: Glycomark and Fructosamine Levels Measured Throughout the Study
timeFrame: Change from baseline to 16 weeks
measure: Seven-point Glucose at Randomization and Throughout the Study
timeFrame: Change from baseline to 16 weeks
measure: Glycemic Excursions and Variability as Assessed Through Continuous Glucose Monitoring (CGM)
timeFrame: Change from baseline to 16 weeks
measure: Changes in Body Weight at 16 Weeks
timeFrame: Change from baseline to 16 weeks
measure: Treatment Satisfaction as Assessed by Subject Treatment and Health Outcomes Questionnaires
timeFrame: Change from baseline to 16 weeks
measure: Total Number of Cough Episodes
timeFrame: Baseline to Week 16
measure: Severe Hypoglycemic Event Rate
timeFrame: Baseline to Week 16
measure: Mild or Moderate Hypoglycemic Event Rate
timeFrame: Baseline to Week 16
measure: Number of Subjects Reporting Cough Episodes
timeFrame: Baseline to Week 16
measure: Number of Subjects Reporting Intermittent Coughing Episodes
timeFrame: Baseline to Week 16
measure: Number of Single Coughing Episodes
timeFrame: Baseline to Week 16
measure: Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation
timeFrame: Baseline to Week 16
measure: Baseline Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline
measure: Week 16 Forced Expiratory Volume in 1 Second
timeFrame: Week 16
measure: Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second
timeFrame: Baseline to Week 16
measure: Week 20 (Follow-up) Forced Expiratory Volume in 1 Second
timeFrame: Week 20 (Follow-up)
measure: Week 20 (Follow-up) Change From Baseline in Forced Expiratory Volume in 1 Second
timeFrame: Baseline to Week 20
measure: Baseline Forced Vital Capacity (FVC)
timeFrame: Baseline
measure: Week 16 Forced Vital Capacity
timeFrame: Week 16
measure: Week 16 Change From Baseline Forced Vital Capacity
timeFrame: Baseline to Week 16
measure: Week 20 (Follow-up) Forced Vital Capacity
timeFrame: Week 20
measure: Week 20 (Follow-up) Change From Baseline in Forced Vital Capacity
timeFrame: Baseline to Week 20
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research Inc
state: Alabama
city: Fresno
country: United States
facility: Valley Research
state: California
city: Long Beach
country: United States
facility: Health Care Partners Medical Group
state: California
city: Tustin
country: United States
facility: Diabetes Research Center
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Atlanta
country: United States
facility: Laureate Clinical Research Group
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Dunwoody
country: United States
facility: Alta Pharmaceutical Research Center
state: Georgia
city: Chicago
country: United States
facility: John H Stoger Jr Hospital of Cook County
state: Illinois
city: Michigan City
country: United States
facility: LaPorte County Institute for Clinical Research Inc.
state: Indiana
city: Edina
country: United States
facility: Radiant Research Inc (Minneapolis)
state: Minnesota
city: St Peters
country: United States
facility: Amin Radparvar's Private Practice
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Research Center
state: Montana
city: Omaha
country: United States
facility: Creighton Diabetes Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico HCS
state: New Mexico
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: North Shore Diabetes and Endocrine Associates
state: New York
city: Greenville
country: United States
facility: Endocrine Research Physicians East PA
state: North Carolina
city: Mentor
country: United States
facility: Your Diabetes Endocrine Nutrition Group, Inc.
state: Ohio
city: Portland
country: United States
facility: Legacy Clinical Research
state: Oregon
city: Portland
country: United States
facility: OHSU Diabetes Center Research Oregon Health & Science University
state: Oregon
city: Memphis
country: United States
facility: The Endocrine Clinic
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
city: Dallas
country: United States
facility: Baylor Endocrine Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: SAM Clinical Research Center
state: Texas
city: Magna
country: United States
facility: Exodus Healthcare Network
state: Utah
city: South Burlington
country: United States
facility: Diabetes Research Center -Fletcher Allen Health Care
state: Vermont
Study officials:
References: