Clinical Trial Evaluating the Efficacy and Safety of Technosphere® Inhalation Insulin (TI) Inhalation Powder Using the Gen2 Inhaler

Phase 3

Terminated

Conditions: Type 2 Diabetes

Interventions: Drug: Technosphere® Insulin Inhalation Powder
Drug: Insulin Aspart
Drug: Insulin Glargine

Registration Number: NCT01196104

Lead Sponsor: Mannkind Corporation

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 39

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)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Technosphere® Insulin Inhalation Powder (TI)	Technosphere® Insulin Inhalation Powder	Insulin Glargine and Technosphere® Insulin Inhalation Powder
Comparator	Insulin Aspart	Insulin Glargine and Insulin Aspart
Technosphere® Insulin Inhalation Powder (TI)	Insulin Glargine	Insulin Glargine and Technosphere® Insulin Inhalation Powder
Comparator	Insulin Glargine	Insulin Glargine and Insulin Aspart

Primary Outcome Measures

Name	Time	Method
Change in HbA1c (%) From Baseline to Week 16	Baseline to Week 16	Change from Baseline in glycated hemoglobin at Week 16

Secondary Outcome Measures

Name	Time	Method
Glycomark and Fructosamine Levels Measured Throughout the Study	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Seven-point Glucose at Randomization and Throughout the Study	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Glycemic Excursions and Variability as Assessed Through Continuous Glucose Monitoring (CGM)	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Changes in Body Weight at 16 Weeks	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
To Evaluate the Effect of Each Treatment on HbA1c	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Comparison of Fasting Plasma Glucose (FPG) Levels at Randomization and Throughout the Study	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Comparison of Post-prandial Glucose (PPG) Levels at Randomization and Throughout the Study	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Total Number of Cough Episodes	Baseline to Week 16	Total number of times patients coughed once, intermittently or continuously (inclusive)
Severe Hypoglycemic Event Rate	Baseline to Week 16	Severe hypoglycemic event rate, ie, total number of events divided by subject-months of observation Severe hypoglycemia is defined as a subject who requires the assistance of another individual (not merely requested) and either: * SMBG levels ≤ 36 mg/dL OR * There is a prompt response to the administration of carbohydrate, glucagon, or other resuscitative measures
Treatment Satisfaction as Assessed by Subject Treatment and Health Outcomes Questionnaires	Change from baseline to 16 weeks	Not analyzed due to early termination of the trial.
Baseline Forced Expiratory Volume in 1 Second (FEV1)	Baseline	Baseline FEV1
Mild or Moderate Hypoglycemic Event Rate	Baseline to Week 16	Mild or moderate hypoglycemic event rate, ie, total number of events divided by subject-months of observation Nonsevere hypoglycemia is defined as a subject: * SMBG levels \< 70 mg/dL AND/OR * Symptoms that are relieved by the self-administration of carbohydrates
Week 16 Forced Expiratory Volume in 1 Second	Week 16	Week 16 FEV1
Week 16 Change From Baseline Forced Vital Capacity	Baseline to Week 16	Week 16 Change from Baseline FVC
Number of Subjects Reporting Cough Episodes	Baseline to Week 16	Number of Subjects Reporting Cough Episodes
Week 16 Forced Vital Capacity	Week 16	Week 16 FVC
Week 20 (Follow-up) Forced Vital Capacity	Week 20	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) FVC
Number of Subjects Reporting Intermittent Coughing Episodes	Baseline to Week 16	Number of subjects reporting Intermittent Coughing Episodes
Number of Single Coughing Episodes	Baseline to Week 16	Total number of times patients coughed only once
Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation	Baseline to Week 16
Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second	Baseline to Week 16	Week 16 Change from Baseline in FEV1
Week 20 (Follow-up) Forced Expiratory Volume in 1 Second	Week 20 (Follow-up)	Week 20 (Follow-up) FEV1, 4 weeks after discontinuation of study treatment
Week 20 (Follow-up) Change From Baseline in Forced Expiratory Volume in 1 Second	Baseline to Week 20	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FEV1
Baseline Forced Vital Capacity (FVC)	Baseline	Baseline FVC
Week 20 (Follow-up) Change From Baseline in Forced Vital Capacity	Baseline to Week 20	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FVC

Trial Locations

Locations (29): Billings Clinic Research Center
🇺🇸
Billings, Montana, United States
Diabetes Research Center -Fletcher Allen Health Care
🇺🇸
South Burlington, Vermont, United States
Coastal Clinical Research Inc
🇺🇸
Mobile, Alabama, United States
Laureate Clinical Research Group
🇺🇸
Atlanta, Georgia, United States
Diablo Clinical Research
🇺🇸
Walnut Creek, California, United States
Alta Pharmaceutical Research Center
🇺🇸
Dunwoody, Georgia, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Health Care Partners Medical Group
🇺🇸
Long Beach, California, United States
Your Diabetes Endocrine Nutrition Group, Inc.
🇺🇸
Mentor, Ohio, United States
North Shore Diabetes and Endocrine Associates
🇺🇸
New Hyde Park, New York, United States
Legacy Clinical Research
🇺🇸
Portland, Oregon, United States
OHSU Diabetes Center Research Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Exodus Healthcare Network
🇺🇸
Magna, Utah, United States
University of New Mexico HCS
🇺🇸
Albuquerque, New Mexico, United States
Winthrop University Hospital
🇺🇸
Mineola, New York, United States
Diabetes Research Center
🇺🇸
Tustin, California, United States
Atlanta Diabetes Associates
🇺🇸
Atlanta, Georgia, United States
Endocrine Research Physicians East PA
🇺🇸
Greenville, North Carolina, United States
Creighton Diabetes Center
🇺🇸
Omaha, Nebraska, United States
The Endocrine Clinic
🇺🇸
Memphis, Tennessee, United States
Baylor Endocrine Center
🇺🇸
Dallas, Texas, United States
SAM Clinical Research Center
🇺🇸
San Antonio, Texas, United States
Radiant Research Inc (Minneapolis)
🇺🇸
Edina, Minnesota, United States
Valley Research
🇺🇸
Fresno, California, United States
John H Stoger Jr Hospital of Cook County
🇺🇸
Chicago, Illinois, United States
Amin Radparvar's Private Practice
🇺🇸
St Peters, Missouri, United States
LaPorte County Institute for Clinical Research Inc.
🇺🇸
Michigan City, Indiana, United States
Dallas Diabetes & Endocrine Center
🇺🇸
Dallas, Texas, United States
Washington University School of Medicine
🇺🇸
St. Louis, Missouri, United States