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Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period

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ClinicalTrials.gov Identifier: NCT01445951
Recruitment Status : Completed
First Posted : October 4, 2011
Results First Posted : October 22, 2014
Last Update Posted : October 22, 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
Condition Type 1 Diabetes Mellitus
Interventions Drug: Technosphere® Insulin with MedTone C Inhaler
Drug: Technosphere ®Insulin with Gen2 Inhaler
Drug: Insulin Aspart in combination with a basal insulin
Enrollment 518
Recruitment Details First Patient enrolled Sept 2011. Multi-national trial conducted in US, Russia, Ukraine and Brazil.
Pre-assignment Details 3 week Screening Period prior to run-in (basal insulin optimization period). 1401 Screened / 621 Eligible of which 614 entered the run-in period. 538 met randomization criteria at end of run-in of which 518 were randomized.
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Period Title: Overall Study
Started 174 174 170
Completed 130 138 151
Not Completed 44 36 19
Reason Not Completed
Adverse Event             16             9             0
Protocol Violation             2             2             2
Withdrawal by Subject             21             16             8
Physician Decision             3             1             0
Lost to Follow-up             1             2             4
Pregnancy             0             1             4
Death             0             0             1
Non-compliance with study drug             1             2             0
Non-compliance with protocol             0             1             0
Sponsor decision - subject travel             0             1             0
Cough             0             1             0
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin Total
Hide Arm/Group Description Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient Total of all reporting groups
Overall Number of Baseline Participants 174 174 170 518
Hide Baseline Analysis Population Description
Full analysis set
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 170 participants 518 participants
18-30 years 56 48 46 150
31-49 years 93 84 88 265
50-64 years 18 33 28 79
>= 65 years 7 9 8 24
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 170 participants 518 participants
Female
97
  55.7%
94
  54.0%
96
  56.5%
287
  55.4%
Male
77
  44.3%
80
  46.0%
74
  43.5%
231
  44.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 170 participants 518 participants
Hispanic or Latino
17
   9.8%
22
  12.6%
18
  10.6%
57
  11.0%
Not Hispanic or Latino
157
  90.2%
152
  87.4%
152
  89.4%
461
  89.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 170 participants 518 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.6%
1
   0.6%
0
   0.0%
2
   0.4%
Native Hawaiian or Other Pacific Islander
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Black or African American
8
   4.6%
5
   2.9%
3
   1.8%
16
   3.1%
White
164
  94.3%
167
  96.0%
166
  97.6%
497
  95.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.6%
1
   0.6%
2
   0.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 174 participants 174 participants 170 participants 518 participants
United States 71 69 67 207
Brazil 14 15 13 42
Ukraine 44 38 38 120
Russian Federation 45 52 52 149
Duration of Diabetes  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 174 participants 174 participants 170 participants 518 participants
16.0
(1.1 to 57.3)
17.7
(1.1 to 49.5)
16.7
(1.0 to 42.2)
16.8
(1.0 to 57.3)
Weight  
Mean (Full Range)
Unit of measure:  Kg
Number Analyzed 174 participants 174 participants 170 participants 518 participants
75.7
(41.7 to 129.4)
76.8
(47.6 to 124.0)
72.6
(46.6 to 120.2)
75.1
(41.7 to 129.4)
BMI  
Mean (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 174 participants 174 participants 170 participants 518 participants
26.0
(16.6 to 38.6)
26.2
(18.1 to 36.4)
25.4
(17.4 to 37.2)
25.9
(16.6 to 38.6)
Fasting Plasma Glucose  
Mean (Full Range)
Unit of measure:  mg/dL
Number Analyzed 174 participants 174 participants 170 participants 518 participants
155.0
(21.0 to 403.0)
144.3
(43.0 to 358.0)
151.2
(23.0 to 375.0)
150.2
(21.0 to 403.0)
HbA1c  
Mean (Full Range)
Unit of measure:  Percent of hemoglobin
Number Analyzed 174 participants 174 participants 170 participants 518 participants
7.98
(6.20 to 10.60)
8.00
(6.10 to 10.20)
7.88
(5.80 to 10.10)
7.95
(5.80 to 10.60)
1.Primary Outcome
Title Change From Baseline to Week 24 in HbA1c
Hide Description Effect of treatment as measured by change from baseline in glycated hemoglobin (HbA1c). Primary treatment difference is TI-Gen2 vs. Insulin Aspart at Week 24
Time Frame Baseline to Week 24
Hide Outcome Measure Data
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Full analysis set
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 174 170
Least Squares Mean (Standard Error)
Unit of Measure: Percent of hemoglobin
-0.21  (0.062) -0.29  (0.061) -0.40  (0.060)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments MMRM (mixed model repeated measures) model with auto-regression (1): HbA1c = Baseline HbA1c + region + basal insulin stratum + visit + treatment + (visit*treatment)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority with 0.4 margin
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.02 to 0.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.086
Estimation Comments [Not Specified]
2.Secondary Outcome
Title FEV1 Change From Baseline to Week 24
Hide Description Forced Expiratory Volume in 1 second - change from baseline to week 24
Time Frame Baseline to Week 24
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Safety population
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 173 171
Least Squares Mean (Standard Error)
Unit of Measure: Liters
-0.07  (0.012) -0.08  (0.012) -0.04  (0.011)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Technosphere Insulin-MedTone + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.016
Estimation Comments Mixed Model Repeated Measure (MMRM): FEV1 = Baseline FEV1 + Age + Gender + Race + Baseline Height + Visit + Treatment + (Visit*Treatment)
3.Secondary Outcome
Title FPG Change From Baseline to Week 24
Hide Description Comparison of mean change from Baseline to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results)
Time Frame Baseline to Week 24
Hide Outcome Measure Data
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Full analysis set
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 174 170
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-25.27  (7.62) 7.15  (7.53) 10.15  (7.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -35.42
Confidence Interval (2-Sided) 95%
-56.25 to -14.59
Parameter Dispersion
Type: Standard Error of the mean
Value: 10.622
Estimation Comments MMRM: FPG = Baseline FPG + Region + Basal insulin stratum + Visit + Treatment + (Visit*Treatment)
4.Secondary Outcome
Title Mean 7-point Glucose Baseline Values
Hide Description Mean 7-point glucose at baseline
Time Frame Baseline
Hide Outcome Measure Data
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Full analysis set
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 174 170
Mean (Standard Deviation)
Unit of Measure: mg/dL
Before breakfast 154.1  (38.85) 151.8  (40.32) 147.0  (39.09)
After breakfast 173.3  (48.77) 173.5  (48.36) 162.6  (49.50)
Before lunch 158.0  (47.39) 156.6  (42.91) 142.3  (37.86)
After lunch 169.5  (52.25) 169.7  (49.23) 157.6  (48.08)
Before dinner 169.9  (47.12) 168.1  (45.24) 154.0  (46.53)
After dinner 176.2  (51.55) 177.0  (53.17) 158.5  (47.64)
Bedtime 178.3  (51.38) 175.1  (43.99) 164.4  (49.97)
5.Secondary Outcome
Title Mean 7-point Glucose Week 24 Values
Hide Description [Not Specified]
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 174 170
Mean (Standard Deviation)
Unit of Measure: mg/dL
Before breakfast 148.2  (40.64) 147.9  (43.17) 155.3  (48.44)
After breakfast 169.7  (67.53) 164.1  (60.97) 163.0  (58.00)
Before lunch 168.2  (56.93) 165.9  (59.95) 149.1  (50.58)
After lunch 173.7  (57.09) 163.1  (50.92) 158.2  (50.04)
Before dinner 177.8  (59.96) 177.3  (56.71) 156.8  (48.30)
After dinner 180.8  (63.50) 168.2  (60.77) 157.8  (52.62)
Bedtime 185.2  (62.36) 185.6  (54.96) 175.4  (57.37)
6.Secondary Outcome
Title Change in Body Weight From Baseline to Week 24
Hide Description Change in body weight from Baseline to Week 24
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (subjects with data available at Baseline and at Week 24)
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 132 140 153
Least Squares Mean (Standard Error)
Unit of Measure: kg
-0.39  (0.438) -0.19  (0.428) 0.93  (0.441)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0102
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA: Weight change from baseline = Baseline weight + Change from baseline in HbA1c + Region + Basal insulin stratum + Treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.32
Confidence Interval (2-Sided) 95%
-2.33 to -0.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.512
Estimation Comments ANCOVA: Weight change from baseline = Baseline weight + Change from baseline in HbA1c + Region + Basal insulin stratum + Treatment
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin
Comments Within treatment analysis of change from Baseline comparing if change was different from zero
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4955
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-MedTone + Basal Insulin
Comments Within treatment analysis of change from Baseline comparing if change was different from zero
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6807
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Insulin Aspart + Basal Insulin
Comments Within treatment analysis of change from Baseline comparing if change was different from zero
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0079
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Proportion of Responders Achieving HbA1c <= 7.0%
Hide Description Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%
Time Frame Week 24
Hide Outcome Measure Data
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Full analysis set
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 131 138 150
Measure Type: Number
Unit of Measure: percentage of participants
18.3 21.7 30.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0158
Comments [Not Specified]
Method Regression, Logistic
Comments Model: Treatment + Basal insulin stratum + Region + Baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.449
Confidence Interval (2-Sided) 95%
0.23 to 0.86
Estimation Comments Gen2 in the numerator, Aspart in the denominator
8.Other Pre-specified Outcome
Title Incidence of Total Hypoglycemia
Hide Description Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 173 171
Measure Type: Number
Unit of Measure: percentage of participants
96.0 96.0 99.4
9.Other Pre-specified Outcome
Title Incidence of Severe Hypoglycemia
Hide Description Severe Hypoglycemia defined as: Requiring 3rd party assistance.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 173 171
Measure Type: Number
Unit of Measure: percentage of participants
18.4 21.4 29.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0156
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic model with affects for Region, Basal insulin stratum, and Treatment
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.5328
Confidence Interval (2-Sided) 95%
0.3198 to 0.8877
Estimation Comments [Not Specified]
10.Other Pre-specified Outcome
Title Total Hypoglycemia Event Rate
Hide Description Number of Hypoglycemic Events/Total Subject Exposure Time (in months)
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 173 171
Measure Type: Number
Unit of Measure: Events/Subject-Month
9.80 10.30 13.97
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative Binomial Regression
Comments Model: Region + Basal Insulin Stratum + Treatment + Exposure Time
11.Other Pre-specified Outcome
Title Severe Hypoglycemia Event Rate
Hide Description Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin-MedTone + Basal Insulin Insulin Aspart + Basal Insulin
Hide Arm/Group Description:
Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient
Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Number of Participants Analyzed 174 173 171
Measure Type: Number
Unit of Measure: Events/Subject-Month
8.05 9.99 14.45
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Technosphere Insulin-Gen2 + Basal Insulin, Insulin Aspart + Basal Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1022
Comments [Not Specified]
Method Negative Binomial Regression
Comments Model: Region + Basal Insulin Stratum + Treatment + Exposure Time
Time Frame Baseline to Week 24
Adverse Event Reporting Description Adverse Events (AE) are summarized according to how subjects were treated, not randomized. One subject that was randomized to the Technosphere Insulin-MedTone + Basal Insulin arm was treated with Insulin aspart + Basal Insulin throughout the trial.
 
Arm/Group Title Technosphere ® Insulin-Gen2 Group Technosphere® Insulin With MedTone C Inhaler Aspart Group
Hide Arm/Group Description

Subject will receive Technosphere Insulin with Gen2 Inhaler and remain on the basal insulin they were taking prior to study entry

Technosphere ®Insulin with Gen2 Inhaler: Inhalation Powder and injectable insulin

Subjects will receive TI with the MedToneC inhaler and remain on the basal insulin they were taking prior to study entry

Technosphere® Insulin with MedTone C Inhaler: Inhalation Powder and injectable insulin

Subjects will receive insulin aspart and remain on the basal insulin they were taking prior to study entry

Insulin Aspart in combination with a basal insulin: Injectable insulin

All-Cause Mortality
Technosphere ® Insulin-Gen2 Group Technosphere® Insulin With MedTone C Inhaler Aspart Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Technosphere ® Insulin-Gen2 Group Technosphere® Insulin With MedTone C Inhaler Aspart Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/174 (2.87%)   9/173 (5.20%)   7/171 (4.09%) 
General disorders       
Chest Discomfort  1  0/174 (0.00%)  1/173 (0.58%)  0/171 (0.00%) 
Drowning  1  0/174 (0.00%)  0/173 (0.00%)  1/171 (0.58%) 
Infections and infestations       
Cytomegalovirus Infection  1  1/174 (0.57%)  0/173 (0.00%)  0/171 (0.00%) 
Appendicitis  1  0/174 (0.00%)  0/173 (0.00%)  1/171 (0.58%) 
Injury, poisoning and procedural complications       
Joint Dislocation  1  1/174 (0.57%)  0/173 (0.00%)  0/171 (0.00%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  1/174 (0.57%)  2/173 (1.16%)  1/171 (0.58%) 
Musculoskeletal and connective tissue disorders       
Spinal Osteoarthritis  1  0/174 (0.00%)  0/173 (0.00%)  1/171 (0.58%) 
Nervous system disorders       
Hypoglycaemic Unconsciousness  1  1/174 (0.57%)  4/173 (2.31%)  2/171 (1.17%) 
Hypoglycaemic Seizure  1  1/174 (0.57%)  1/173 (0.58%)  1/171 (0.58%) 
Psychiatric disorders       
Mental Status Changes  1  0/174 (0.00%)  0/173 (0.00%)  1/171 (0.58%) 
Reproductive system and breast disorders       
Cervical Polyp  1  0/174 (0.00%)  1/173 (0.58%)  0/171 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Bronchial Hyperreactivity  1  1/174 (0.57%)  0/173 (0.00%)  0/171 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Technosphere ® Insulin-Gen2 Group Technosphere® Insulin With MedTone C Inhaler Aspart Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   81/174 (46.55%)   74/173 (42.77%)   50/171 (29.24%) 
Gastrointestinal disorders       
Diarrhoea  1  4/174 (2.30%)  2/173 (1.16%)  5/171 (2.92%) 
Vomiting  1  2/174 (1.15%)  3/173 (1.73%)  5/171 (2.92%) 
Nausea  1  1/174 (0.57%)  5/173 (2.89%)  6/171 (3.51%) 
Infections and infestations       
Upper Respiratory Tract Infection  1  14/174 (8.05%)  16/173 (9.25%)  12/171 (7.02%) 
Bronchitis  1  6/174 (3.45%)  1/173 (0.58%)  4/171 (2.34%) 
Nasopharyngitis  1  5/174 (2.87%)  13/173 (7.51%)  12/171 (7.02%) 
Influenza  1  2/174 (1.15%)  9/173 (5.20%)  3/171 (1.75%) 
Urinary Tract Infection  1  1/174 (0.57%)  6/173 (3.47%)  3/171 (1.75%) 
Investigations       
Blood Creatine Phosphokinase Increase  1  0/174 (0.00%)  2/173 (1.16%)  4/171 (2.34%) 
Nervous system disorders       
Headache  1  7/174 (4.02%)  5/173 (2.89%)  4/171 (2.34%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  55/174 (31.61%)  39/173 (22.54%)  4/171 (2.34%) 
Dyspnoea  1  7/174 (4.02%)  0/173 (0.00%)  0/171 (0.00%) 
Throat Irritation  1  5/174 (2.87%)  3/173 (1.73%)  1/171 (0.58%) 
Oropharyngeal Pain  1  3/174 (1.72%)  6/173 (3.47%)  3/171 (1.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
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
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: MannKind Corporation
Phone: 201-983-5000
EMail: aboss@mannkindcorp.com
Layout table for additonal information
Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT01445951     History of Changes
Other Study ID Numbers: MKC-TI-171
First Submitted: September 30, 2011
First Posted: October 4, 2011
Results First Submitted: July 22, 2014
Results First Posted: October 22, 2014
Last Update Posted: October 22, 2014