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

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01196104
• Other study ID #: MKC-TI-162
• Status: Terminated
• Phase: Phase 3
• First received: August 30, 2010
• Last updated: October 21, 2014
• Start date: September 2010
• Est. completion date: March 2012

Study information

• Verified date: October 2014
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: March 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Technosphere® Insulin Inhalation Powder

• Insulin Aspart
Usual Care
• Insulin Glargine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (%) From Baseline to Week 16	Change from Baseline in glycated hemoglobin at Week 16	Baseline to Week 16	No
Secondary	To Evaluate the Effect of Each Treatment on HbA1c	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Comparison of Fasting Plasma Glucose (FPG) Levels at Randomization and Throughout the Study	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Comparison of Post-prandial Glucose (PPG) Levels at Randomization and Throughout the Study	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Glycomark and Fructosamine Levels Measured Throughout the Study	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Seven-point Glucose at Randomization and Throughout the Study	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Glycemic Excursions and Variability as Assessed Through Continuous Glucose Monitoring (CGM)	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Changes in Body Weight at 16 Weeks	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Treatment Satisfaction as Assessed by Subject Treatment and Health Outcomes Questionnaires	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks	No
Secondary	Total Number of Cough Episodes	Total number of times patients coughed once, intermittently or continuously (inclusive)	Baseline to Week 16	Yes
Secondary	Severe Hypoglycemic Event Rate	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	Baseline to Week 16	Yes
Secondary	Mild or Moderate Hypoglycemic Event Rate	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	Baseline to Week 16	Yes
Secondary	Number of Subjects Reporting Cough Episodes	Number of Subjects Reporting Cough Episodes	Baseline to Week 16	Yes
Secondary	Number of Subjects Reporting Intermittent Coughing Episodes	Number of subjects reporting Intermittent Coughing Episodes	Baseline to Week 16	Yes
Secondary	Number of Single Coughing Episodes	Total number of times patients coughed only once	Baseline to Week 16	Yes
Secondary	Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation		Baseline to Week 16	Yes
Secondary	Baseline Forced Expiratory Volume in 1 Second (FEV1)	Baseline FEV1	Baseline	Yes
Secondary	Week 16 Forced Expiratory Volume in 1 Second	Week 16 FEV1	Week 16	Yes
Secondary	Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second	Week 16 Change from Baseline in FEV1	Baseline to Week 16	Yes
Secondary	Week 20 (Follow-up) Forced Expiratory Volume in 1 Second	Week 20 (Follow-up) FEV1, 4 weeks after discontinuation of study treatment	Week 20 (Follow-up)	Yes
Secondary	Week 20 (Follow-up) Change From Baseline in Forced Expiratory Volume in 1 Second	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FEV1	Baseline to Week 20	Yes
Secondary	Baseline Forced Vital Capacity (FVC)	Baseline FVC	Baseline	Yes
Secondary	Week 16 Forced Vital Capacity	Week 16 FVC	Week 16	Yes
Secondary	Week 16 Change From Baseline Forced Vital Capacity	Week 16 Change from Baseline FVC	Baseline to Week 16	Yes
Secondary	Week 20 (Follow-up) Forced Vital Capacity	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) FVC	Week 20	Yes
Secondary	Week 20 (Follow-up) Change From Baseline in Forced Vital Capacity	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) Change from Baseline in FVC	Baseline to Week 20	Yes