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Safety of Inhaled Insulin With Type 1 and Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT00308737
Recruitment Status : Completed
First Posted : March 30, 2006
Results First Posted : October 16, 2014
Last Update Posted : October 16, 2014
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diabetes, Type 1
Diabetes, Type 2
Interventions Drug: Technosphere® Insulin Inhalation Powder
Drug: Usual Care
Enrollment 2053

Recruitment Details First subject enrolled July 25, 2005 Multi-national trial conducted in Canada, Czech Republic, Poland, Russia, Spain, Ukraine, UK, and US
Pre-assignment Details

Subjects were required to meet all inclusion/exclusion criteria 3741 screened/2053 eligible of which all were randomized, including 164 non-diabetics - 1688 screen failures

17 diabetics randomized but not dosed

1 non-diabetic elected not to participate

Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description Technosphere Insulin with or without basal insulin, or oral anti-diabetic medications, or any combination of the previous. Usual care may consist of oral anti-diabetic medications, basal insulin, subcutaneous prandial insulin, or any combination of the previous. Subjects without abnormalities in glucose control
Period Title: Overall Study
Started 938 951 164
Completed 475 662 127
Not Completed 463 289 37
Reason Not Completed
Adverse Event             104             9             0
Death             4             3             0
Lost to Follow-up             56             80             5
Physician Decision             15             2             1
Protocol Violation             34             9             5
Withdrawal by Subject             218             166             18
Various             32             20             8
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes Total
Hide Arm/Group Description Technosphere Insulin Usual care Subjects without abnormalities in glucose control Total of all reporting groups
Overall Number of Baseline Participants 923 949 163 2035
Hide Baseline Analysis Population Description
Safety population, excluding subjects who were not dosed with study medication (17 diabetics randomized but not dosed, 1 non-diabetic elected not to participate)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 923 participants 949 participants 163 participants 2035 participants
50.8  (11.55) 50.4  (11.62) 38.2  (12.59) 49.6  (12.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 923 participants 949 participants 163 participants 2035 participants
Female
366
  39.7%
371
  39.1%
92
  56.4%
829
  40.7%
Male
557
  60.3%
578
  60.9%
71
  43.6%
1206
  59.3%
Body mass index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per meter squared
Number Analyzed 923 participants 949 participants 163 participants 2035 participants
29.87  (5.366) 29.76  (5.035) 25.27  (4.494) 29.5  (5.29)
[1]
Measure Description: Body mass index
HbA1c   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 923 participants 949 participants 163 participants 2035 participants
8.7  (1.39) 8.7  (1.38) 0  (0) 8.4  (1.61)
[1]
Measure Description: Glycated hemoglobin
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 923 participants 949 participants 163 participants 2035 participants
87.69  (18.628) 87.53  (17.638) 74.35  (16.204) 86.6  (18.33)
[1]
Measure Description: Weight in kilograms
1.Primary Outcome
Title Change From Baseline to Month 24 in Forced Expiratory Volume in 1 Second (FEV1) by MMRM for TI vs Usual Care
Hide Description Change from Baseline to End of Study in FEV1 by MMRM
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT)
Arm/Group Title Technosphere® Insulin Usual Care
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Overall Number of Participants Analyzed 730 824
Mean (Standard Deviation)
Unit of Measure: liters
-0.16  (0.208) -0.12  (0.211)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Mixed model repeated measures with fixed effects diabetes type, visit, pooled site and treatment and baseline FEV1 as a covariate
Type of Statistical Test Non-Inferiority or Equivalence
Comments Comparison of TI + Usual Care to Usual Care only
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Repeated measures
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.037
Confidence Interval (2-Sided) 95%
0.014 to 0.060
Estimation Comments [Not Specified]
2.Primary Outcome
Title FEV1 Decrease of ≥ 15% From Baseline Value at Last Measurement for TI vs Usual Care
Hide Description FEV1 decrease of ≥ 15% from Baseline value at last measurement
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT)
Arm/Group Title Technosphere® Insulin Usual Care
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Overall Number of Participants Analyzed 730 824
Measure Type: Number
Unit of Measure: Participants
42 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Logistic regression excluding non-diabetics
Type of Statistical Test Non-Inferiority or Equivalence
Comments The null hypothesis tested was that the difference in incidence of a decrease of ≥ 15% in FEV1 between the treatment groups not be greater than 5% for TI when compared with the usual care treatment group. Assuming an incidence rate of 15% for FEV1 and a noninferiority criterion of a 5% difference in incidence between the treatment groups, approximately 625 subjects per group were required for 80% power and an alpha of 5% (1 tailed).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value -2.4767
Confidence Interval (2-Sided) 95%
-4.5578 to -0.3956
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Last Measurement in FEV1 for TI vs Usual Care
Hide Description Change from Baseline to last measurement(Month 24) in FEV1
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT) with Last Observation Carried Forward (LOCF)
Arm/Group Title Technosphere® Insulin Usual Care
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Overall Number of Participants Analyzed 730 824
Least Squares Mean (95% Confidence Interval)
Unit of Measure: liters
-0.128
(-0.144 to -0.113)
-0.092
(-0.107 to -0.077)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments ANCOVA model with treatment site, diabetes type, and baseline FEV1
Type of Statistical Test Non-Inferiority or Equivalence
Comments The null hypothesis tested was that the FEV1 change from Baseline for the TI group is no greater than 50 mL/year above the change in the usual care treatment group. Assuming SD of 100 mL/y, 80% power, and 5% (1-tailed) significance level, it was determined that 50 subjects were required for each of the diabetes treatment groups. Final sample size was selected for the incidence of a >= 15% decrease in FEV1 end point.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.037
Confidence Interval (2-Sided) 95%
0.016 to 0.057
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Month 24 in Forced Vital Capacity (FVC) by MMRM
Hide Description Change from Baseline to Month 24 in FVC by MMRM
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat (ITT)
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 730 824 145
Mean (Standard Deviation)
Unit of Measure: liters
-0.14  (0.242) -0.11  (0.262) -0.09  (0.210)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Mixed model repeated measures with fixed effects diabetes type, visit, pooled site and treatment and baseline FVC as a covariate
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Repeated measures
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.034
Confidence Interval (2-Sided) 95%
0.008 to 0.061
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Month 24 in Total Lung Capacity (TLC) by MMRM
Hide Description Change from baseline to Month 24 in TLC by MMRM
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
participants in ITT population with available data
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 717 817 144
Mean (Standard Deviation)
Unit of Measure: liters
-0.05  (0.321) -0.07  (0.322) -0.02  (0.297)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Mixed model repeated measures with fixed effects diabetes type, visit, pooled site, and treatment and baseline TLC as a covariate
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Repeated measures
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.005
Confidence Interval (2-Sided) 95%
-0.042 to 0.031
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to Month 24 in Hemoglobin Corrected DLco by MMRM
Hide Description Change from baseline to Month 24 in hemoglobin-corrected DLco by MMRM
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
participants in ITT population with available data
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 723 818 144
Mean (Standard Deviation)
Unit of Measure: mL/min/mmHg
-1.60  (2.830) -1.36  (2.862) -1.33  (3.203)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Mixed model repeated measures with fixed effects diabetes type, visit, pooled site, and treatment and baseline TLC as a covariate
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments Repeated measures
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.269
Confidence Interval (2-Sided) 95%
-0.037 to 0.574
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Forced Vital Capacity (FVC) Decrease of ≥ 15% From Baseline Value at Last Measurement
Hide Description FVC Decrease of ≥15% from Baseline Value at Last Measurement
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
participants in ITT population with available data
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 730 824 145
Measure Type: Number
Unit of Measure: participants
23 17 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Logistic regression excluding non-diabetics
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6475
Confidence Interval (2-Sided) 95%
0.3432 to 1.2219
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Total Lung Capacity (TLC) Decrease of ≥ 15% From Baseline Value at Last Measurement
Hide Description TLC Decrease of ≥ 15% from Baseline Value at Last Measurement
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
participants in ITT population with available data
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 717 817 144
Measure Type: Number
Unit of Measure: Participants
7 6 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Logistic regression excluding non-diabetics
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.7504
Confidence Interval (2-Sided) 95%
0.2510 to 2.2431
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Hemoglobin-Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Decrease of ≥ 15% From Baseline Value at Last Measurement
Hide Description Hemoglobin-corrected DLco decrease of ≥ 15% from baseline value at last measurement
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
participants in ITT population with available data
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 723 818 144
Measure Type: Number
Unit of Measure: Participants
105 108 20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Logistic regression excluding non-diabetics
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8953
Confidence Interval (2-Sided) 95%
0.6703 to 1.1958
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Hemoglobin-Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Decrease of >3 ml/Min/mmHg From Baseline Value at Last Measurement
Hide Description Hemoglobin-corrected DLco decrease of >3 ml/min/mmHg from baseline value at last measurement
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
participants in ITT population with available data
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 723 818 144
Measure Type: Number
Unit of Measure: Participants
181 181 40
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Logistic regression excluding non-diabetics
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.8509
Confidence Interval (2-Sided) 95%
0.6722 to 1.0770
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Last Measurement for TI vs Usual Care
Hide Description Change from baseline in HbA1c at last measurement
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention to treat (ITT) with last observation carried forward (LOCF)
Arm/Group Title Technosphere® Insulin Usual Care
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Overall Number of Participants Analyzed 725 818
Mean (Standard Deviation)
Unit of Measure: percentage
-0.42  (1.410) -0.49  (1.37)
12.Secondary Outcome
Title Change in Weight From Baseline at Month 24
Hide Description Change from baseline in weight at Month 24
Time Frame Baseline to Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population at Month 24
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description:
Technosphere Insulin
Usual care
Subjects without abnormalities in glucose control
Overall Number of Participants Analyzed 185 664 126
Mean (Standard Deviation)
Unit of Measure: kilograms
1.0  (6.653) 1.64  (5.066) 1.19  (4.457)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere® Insulin, Usual Care
Comments Two sample t-test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.112
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 24 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Technosphere® Insulin Usual Care Non-diabetes
Hide Arm/Group Description Technosphere Insulin Usual care (taking insulin) Subjects without abnormalities in glucose control
All-Cause Mortality
Technosphere® Insulin Usual Care Non-diabetes
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Technosphere® Insulin Usual Care Non-diabetes
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   92/923 (9.97%)   91/949 (9.59%)   5/163 (3.07%) 
Blood and lymphatic system disorders       
Lymphadenopathy  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Thrombocythaemia  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pernicious anaemia  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Cardiac disorders       
Coronary artery disease  1  5/923 (0.54%)  3/949 (0.32%)  0/163 (0.00%) 
Myocardial infarction  1  2/923 (0.22%)  4/949 (0.42%)  0/163 (0.00%) 
Angina unstable  1  1/923 (0.11%)  2/949 (0.21%)  0/163 (0.00%) 
Atrial fibrillation  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Cardiac arrest  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Coronary artery atherosclerosis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Coronary artery occlusion  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Coronary artery stenosis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Myocardial ischaemia  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Acute myocardial infarction  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Aortic valve stenosis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Cardiac failure  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Cardiac failure chronic  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Cardiac failure congestive  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Acute coronary syndrome  1  0/923 (0.00%)  2/949 (0.21%)  0/163 (0.00%) 
Supraventricular tachycardia  1  0/923 (0.00%)  2/949 (0.21%)  0/163 (0.00%) 
Atrial flutter  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Bundle branch block left  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Ear and labyrinth disorders       
Meniere's disease  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Endocrine disorders       
Hypothyroidism  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Eye disorders       
Retinal detachment  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Retinal disorder  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Eye haemorrhage  1  0/923 (0.00%)  2/949 (0.21%)  0/163 (0.00%) 
Glaucoma  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Gastrointestinal disorders       
Pancreatitis acute  1  3/923 (0.33%)  0/949 (0.00%)  0/163 (0.00%) 
Gastritis  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Anal fistula  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Colitis ulcerative  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Duodenal ulcer  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Erosive oesophagitis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Gastric ulcer  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Gastritis erosive  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Gastrointestinal haemorrhage  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Large intestine perforation  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Oesophageal ulcer  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pancreatic cyst  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pancreatitis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Abdominal pain  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Benign colonic polyp  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Gastroduodenitis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Pancreatic necrosis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Pancreatitis chronic  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Peritonitis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Small intestinal obstruction  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
General disorders       
Chest pain  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Generalised oedema  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Non-cardiac chest pain  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  2/923 (0.22%)  1/949 (0.11%)  0/163 (0.00%) 
Cholelithiasis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Cholecystitis acute  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Hepatitis toxic  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Hepatotoxicity  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Cholecystitis chronic  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Gallbladder disorder  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Infections and infestations       
Pneumonia  1  2/923 (0.22%)  4/949 (0.42%)  0/163 (0.00%) 
Diabetic gangrene  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Appendicitis  1  1/923 (0.11%)  1/949 (0.11%)  1/163 (0.61%) 
Pulmonary tuberculosis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Urinary tract infection  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Carbuncle  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Cellulitis streptococcal  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Diverticulitis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Furuncle  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Injection site cellulitis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Otitis media acute  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Parotitis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Perirectal abscess  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pyelonephritis chronic  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Rectal abscess  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Upper respiratory tract infection  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Wound infection  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pyelonephritis  1  0/923 (0.00%)  2/949 (0.21%)  0/163 (0.00%) 
Cellulitis  1  0/923 (0.00%)  1/949 (0.11%)  1/163 (0.61%) 
Arthritis bacterial  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Bacterial sepsis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Bronchitis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Gangrene  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Osteomyelitis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Postoperative infection  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Sepsis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Staphylococcal scalded skin syndrome  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Tonsillitis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Chronic tonsillitis  1  0/923 (0.00%)  0/949 (0.00%)  1/163 (0.61%) 
Injury, poisoning and procedural complications       
Fall  1  1/923 (0.11%)  3/949 (0.32%)  0/163 (0.00%) 
Accidental overdose  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Facial bones fracture  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Hand fracture  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Jaw fracture  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Meniscus lesion  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Overdose  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Rib fracture  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Upper limb fracture  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Road traffic accident  1  0/923 (0.00%)  2/949 (0.21%)  0/163 (0.00%) 
Ankle fracture  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Brain contusion  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Cerebral haemorrhage traumatic  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Head injury  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Hip fracture  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Humerus fracture  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Multiple fractures  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Spinal fracture  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Investigations       
Blood potassium increased  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  9/923 (0.98%)  10/949 (1.05%)  0/163 (0.00%) 
Diabetic ketoacidosis  1  5/923 (0.54%)  4/949 (0.42%)  0/163 (0.00%) 
Hyperglycaemia  1  2/923 (0.22%)  1/949 (0.11%)  0/163 (0.00%) 
Dehydration  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Diabetes mellitus inadequate control  1  1/923 (0.11%)  6/949 (0.63%)  0/163 (0.00%) 
Ketoacidosis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Hypoglycaemic seizure  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Ketosis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Diabetic complication  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc degeneration  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Localised osteoarthritis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Osteoarthritis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Spinal osteoarthritis  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Rheumatoid arthritis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Rotator cuff syndrome  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Intervertebral disc protrusion  1  0/923 (0.00%)  3/949 (0.32%)  0/163 (0.00%) 
Arthritis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Osteochondrosis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Spondylosis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Tenosynovitis  1  0/923 (0.00%)  0/949 (0.00%)  1/163 (0.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Prostate cancer  1  2/923 (0.22%)  1/949 (0.11%)  0/163 (0.00%) 
Breast cancer  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Uterine leiomyoma  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Basal cell carcinoma  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Benign salivary gland neoplasm  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Bile duct cancer  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Ovarian epithelial cancer  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pituitary tumour benign  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Cervix carcinoma  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Benign ovarian tumour  1  0/923 (0.00%)  0/949 (0.00%)  1/163 (0.61%) 
Nervous system disorders       
Loss of consciousness  1  5/923 (0.54%)  1/949 (0.11%)  0/163 (0.00%) 
Cerebrovascular accident  1  1/923 (0.11%)  4/949 (0.42%)  1/163 (0.61%) 
Ischaemic stroke  1  1/923 (0.11%)  1/949 (0.11%)  0/163 (0.00%) 
Carotid artery stenosis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Convulsion  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Epilepsy  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Multiple sclerosis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Transient ischaemic attack  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Hypoglycaemic coma  1  0/923 (0.00%)  2/949 (0.21%)  0/163 (0.00%) 
Radiculitis lumbosacral  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Sciatica  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Psychiatric disorders       
Depression  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Suicide attempt  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Renal and urinary disorders       
Hydronephrosis  1  2/923 (0.22%)  1/949 (0.11%)  0/163 (0.00%) 
Nephrolithiasis  1  1/923 (0.11%)  3/949 (0.32%)  0/163 (0.00%) 
Renal failure acute  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Calculus ureteric  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Renal colic  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Renal failure  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  2/923 (0.22%)  0/949 (0.00%)  0/163 (0.00%) 
Adenomyosis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Atelectasis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Orthopnoea  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Respiratory failure  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Vocal cord polyp  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Pulmonary oedema  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Skin and subcutaneous tissue disorders       
Skin ulcer  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Urticaria  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Vascular disorders       
Aortic stenosis  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Circulatory collapse  1  1/923 (0.11%)  0/949 (0.00%)  0/163 (0.00%) 
Atherosclerosis obliterans  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Extremity necrosis  1  0/923 (0.00%)  1/949 (0.11%)  0/163 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 7.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Technosphere® Insulin Usual Care Non-diabetes
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   559/923 (60.56%)   472/949 (49.74%)   47/163 (28.83%) 
Infections and infestations       
Upper respiratory tract infection  1  119/923 (12.89%)  143/949 (15.07%)  35/163 (21.47%) 
Nasopharyngitis  1  67/923 (7.26%)  69/949 (7.27%)  14/163 (8.59%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  365/923 (39.54%)  370/949 (38.99%)  0/163 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  257/923 (27.84%)  42/949 (4.43%)  5/163 (3.07%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 7.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
MannKind has right to 1st joint multicenter publication. After 1st publication PI may publish data only if PI submits proposed publication to MNKD for review 60 days prior to publication date. MNKD may remove any confidential information. If a multicenter publication is not submitted 12 months after conclusion, abandonment, or termination of the Study at all sites, or if MNKD confirms there will be no multicenter Study publication, PI may publish the Study results subject to MNKD rights herein.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: MannKind Corporation
Phone: 201-983-5000
Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT00308737     History of Changes
Other Study ID Numbers: MKC-TI-030
First Submitted: March 28, 2006
First Posted: March 30, 2006
Results First Submitted: July 22, 2014
Results First Posted: October 16, 2014
Last Update Posted: October 16, 2014