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

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

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Insulin Glargine; Drug: Technosphere® Insulin Inhalation Powder; Drug: Insulin Aspart

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research Inc
  • California
    • Fresno, California, United States, 93720
      • Valley Research
    • Long Beach, California, United States, 90806
      • Health Care Partners Medical Group
    • Tustin, California, United States, 92780
      • Diabetes Research Center
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Laureate Clinical Research Group
    • Atlanta, Georgia, United States, 30309
      • Atlanta Diabetes Associates
    • Dunwoody, Georgia, United States, 30338
      • Alta Pharmaceutical Research Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H Stoger Jr Hospital of Cook County
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • LaPorte County Institute for Clinical Research Inc.
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Radiant Research Inc (Minneapolis)
  • Missouri
    • St Peters, Missouri, United States, 63376
      • Amin Radparvar's Private Practice
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Research Center
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton Diabetes Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico HCS
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New Hyde Park, New York, United States, 11042
      • North Shore Diabetes and Endocrine Associates
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Endocrine Research Physicians East PA
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Your Diabetes Endocrine Nutrition Group, Inc.
  • Oregon
    • Portland, Oregon, United States, 97232
      • Legacy Clinical Research
    • Portland, Oregon, United States, 97239
      • OHSU Diabetes Center Research Oregon Health & Science University
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • The Endocrine Clinic
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor Endocrine Center
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes & Endocrine Center
    • San Antonio, Texas, United States, 78229
      • Sam Clinical Research Center
  • Utah
    • Magna, Utah, United States, 84044
      • Exodus Healthcare Network
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Diabetes Research Center -Fletcher Allen Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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
Experimental: Technosphere® Insulin Inhalation Powder (TI); Insulin Glargine and Technosphere® Insulin Inhalation Powder	Drug: Insulin Glargine; Drug: Technosphere® Insulin Inhalation Powder
Active Comparator: Comparator; Insulin Glargine and Insulin Aspart	Drug: Insulin Glargine; Drug: Insulin Aspart; Usual Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c (%) From Baseline to Week 16	Change from Baseline in glycated hemoglobin at Week 16	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate the Effect of Each Treatment on HbA1c	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks
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
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
Glycomark and Fructosamine Levels Measured Throughout the Study	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks
Seven-point Glucose at Randomization and Throughout the Study	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks
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
Changes in Body Weight at 16 Weeks	Not analyzed due to early termination of the trial.	Change from baseline to 16 weeks
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
Total Number of Cough Episodes	Total number of times patients coughed once, intermittently or continuously (inclusive)	Baseline to Week 16
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
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
Number of Subjects Reporting Cough Episodes	Number of Subjects Reporting Cough Episodes	Baseline to Week 16
Number of Subjects Reporting Intermittent Coughing Episodes	Number of subjects reporting Intermittent Coughing Episodes	Baseline to Week 16
Number of Single Coughing Episodes	Total number of times patients coughed only once	Baseline to Week 16
Number of Cough Episodes Occuring Within 10 Minutes of Drug Inhalation		Baseline to Week 16
Baseline Forced Expiratory Volume in 1 Second (FEV1)	Baseline FEV1	Baseline
Week 16 Forced Expiratory Volume in 1 Second	Week 16 FEV1	Week 16
Week 16 Change From Baseline in Forced Expiratory Volume in 1 Second	Week 16 Change from Baseline in FEV1	Baseline to Week 16
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)
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
Baseline Forced Vital Capacity (FVC)	Baseline FVC	Baseline
Week 16 Forced Vital Capacity	Week 16 FVC	Week 16
Week 16 Change From Baseline Forced Vital Capacity	Week 16 Change from Baseline FVC	Baseline to Week 16
Week 20 (Follow-up) Forced Vital Capacity	Week 20 (Follow-up, 4 weeks after discontinuation of study treatment) FVC	Week 20
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

Collaborators and Investigators

• Sponsor: Mannkind Corporation

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: September 3, 2010
• First Posted (Estimate): September 8, 2010

Study Record Updates

• Last Update Posted (Estimate): October 30, 2014
• Last Update Submitted That Met QC Criteria: October 21, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• 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 Aspart; Insulin Glargine
• Other Study ID Numbers: MKC-TI-162