Trial Outcomes & Findings for Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period (NCT NCT01445951)

NCT ID: NCT01445951

Last Updated: 2014-10-22

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 518 participants
• Primary outcome timeframe: Baseline to Week 24
• Results posted on: 2014-10-22

Participant Flow

First Patient enrolled Sept 2011. Multi-national trial conducted in US, Russia, Ukraine and Brazil.

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.

Participant milestones

Measure	Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Study STARTED	174	174	170
Overall Study COMPLETED	130	138	151
Overall Study NOT COMPLETED	44	36	19

Reasons for withdrawal

Measure	Technosphere Insulin-Gen2 + Basal Insulin Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Overall Study Adverse Event	16	9	0
Overall Study Protocol Violation	2	2	2
Overall Study Withdrawal by Subject	21	16	8
Overall Study Physician Decision	3	1	0
Overall Study Lost to Follow-up	1	2	4
Overall Study Pregnancy	0	1	4
Overall Study Death	0	0	1
Overall Study Non-compliance with study drug	1	2	0
Overall Study Non-compliance with protocol	0	1	0
Overall Study Sponsor decision - subject travel	0	1	0
Overall Study Cough	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=174 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=170 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient	Total n=518 Participants Total of all reporting groups
Age, Customized 18-30 years	56 participants n=93 Participants	48 participants n=4 Participants	46 participants n=27 Participants	150 participants n=483 Participants
Age, Customized 31-49 years	93 participants n=93 Participants	84 participants n=4 Participants	88 participants n=27 Participants	265 participants n=483 Participants
Age, Customized 50-64 years	18 participants n=93 Participants	33 participants n=4 Participants	28 participants n=27 Participants	79 participants n=483 Participants
Age, Customized >= 65 years	7 participants n=93 Participants	9 participants n=4 Participants	8 participants n=27 Participants	24 participants n=483 Participants
Sex: Female, Male Female	97 Participants n=93 Participants	94 Participants n=4 Participants	96 Participants n=27 Participants	287 Participants n=483 Participants
Sex: Female, Male Male	77 Participants n=93 Participants	80 Participants n=4 Participants	74 Participants n=27 Participants	231 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=93 Participants	22 Participants n=4 Participants	18 Participants n=27 Participants	57 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	157 Participants n=93 Participants	152 Participants n=4 Participants	152 Participants n=27 Participants	461 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Black or African American	8 Participants n=93 Participants	5 Participants n=4 Participants	3 Participants n=27 Participants	16 Participants n=483 Participants
Race (NIH/OMB) White	164 Participants n=93 Participants	167 Participants n=4 Participants	166 Participants n=27 Participants	497 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Region of Enrollment United States	71 participants n=93 Participants	69 participants n=4 Participants	67 participants n=27 Participants	207 participants n=483 Participants
Region of Enrollment Brazil	14 participants n=93 Participants	15 participants n=4 Participants	13 participants n=27 Participants	42 participants n=483 Participants
Region of Enrollment Ukraine	44 participants n=93 Participants	38 participants n=4 Participants	38 participants n=27 Participants	120 participants n=483 Participants
Region of Enrollment Russian Federation	45 participants n=93 Participants	52 participants n=4 Participants	52 participants n=27 Participants	149 participants n=483 Participants
Duration of Diabetes	16.0 years n=93 Participants	17.7 years n=4 Participants	16.7 years n=27 Participants	16.8 years n=483 Participants
Weight	75.7 kg n=93 Participants	76.8 kg n=4 Participants	72.6 kg n=27 Participants	75.1 kg n=483 Participants
BMI	26.0 kg/m^2 n=93 Participants	26.2 kg/m^2 n=4 Participants	25.4 kg/m^2 n=27 Participants	25.9 kg/m^2 n=483 Participants
Fasting Plasma Glucose	155.0 mg/dL n=93 Participants	144.3 mg/dL n=4 Participants	151.2 mg/dL n=27 Participants	150.2 mg/dL n=483 Participants
HbA1c	7.98 Percent of hemoglobin n=93 Participants	8.00 Percent of hemoglobin n=4 Participants	7.88 Percent of hemoglobin n=27 Participants	7.95 Percent of hemoglobin n=483 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: Full analysis set

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

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=174 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=170 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Change From Baseline to Week 24 in HbA1c	-0.21 Percent of hemoglobin Standard Error 0.062	-0.29 Percent of hemoglobin Standard Error 0.061	-0.40 Percent of hemoglobin Standard Error 0.060

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Safety population

Forced Expiratory Volume in 1 second - change from baseline to week 24

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=173 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=171 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
FEV1 Change From Baseline to Week 24	-0.07 Liters Standard Error 0.012	-0.08 Liters Standard Error 0.012	-0.04 Liters Standard Error 0.011

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Full analysis set

Comparison of mean change from Baseline to Week 24 visit in fasting plasma glucose (FPG) levels (central laboratory results)

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=174 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=170 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
FPG Change From Baseline to Week 24	-25.27 mg/dL Standard Error 7.62	7.15 mg/dL Standard Error 7.53	10.15 mg/dL Standard Error 7.40

SECONDARY outcome

Timeframe: Baseline

Population: Full analysis set

Mean 7-point glucose at baseline

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=174 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=170 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Mean 7-point Glucose Baseline Values Before breakfast	154.1 mg/dL Standard Deviation 38.85	151.8 mg/dL Standard Deviation 40.32	147.0 mg/dL Standard Deviation 39.09
Mean 7-point Glucose Baseline Values After breakfast	173.3 mg/dL Standard Deviation 48.77	173.5 mg/dL Standard Deviation 48.36	162.6 mg/dL Standard Deviation 49.50
Mean 7-point Glucose Baseline Values Before lunch	158.0 mg/dL Standard Deviation 47.39	156.6 mg/dL Standard Deviation 42.91	142.3 mg/dL Standard Deviation 37.86
Mean 7-point Glucose Baseline Values After lunch	169.5 mg/dL Standard Deviation 52.25	169.7 mg/dL Standard Deviation 49.23	157.6 mg/dL Standard Deviation 48.08
Mean 7-point Glucose Baseline Values Before dinner	169.9 mg/dL Standard Deviation 47.12	168.1 mg/dL Standard Deviation 45.24	154.0 mg/dL Standard Deviation 46.53
Mean 7-point Glucose Baseline Values After dinner	176.2 mg/dL Standard Deviation 51.55	177.0 mg/dL Standard Deviation 53.17	158.5 mg/dL Standard Deviation 47.64
Mean 7-point Glucose Baseline Values Bedtime	178.3 mg/dL Standard Deviation 51.38	175.1 mg/dL Standard Deviation 43.99	164.4 mg/dL Standard Deviation 49.97

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=174 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=170 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Mean 7-point Glucose Week 24 Values Before breakfast	148.2 mg/dL Standard Deviation 40.64	147.9 mg/dL Standard Deviation 43.17	155.3 mg/dL Standard Deviation 48.44
Mean 7-point Glucose Week 24 Values After breakfast	169.7 mg/dL Standard Deviation 67.53	164.1 mg/dL Standard Deviation 60.97	163.0 mg/dL Standard Deviation 58.00
Mean 7-point Glucose Week 24 Values Before lunch	168.2 mg/dL Standard Deviation 56.93	165.9 mg/dL Standard Deviation 59.95	149.1 mg/dL Standard Deviation 50.58
Mean 7-point Glucose Week 24 Values After lunch	173.7 mg/dL Standard Deviation 57.09	163.1 mg/dL Standard Deviation 50.92	158.2 mg/dL Standard Deviation 50.04
Mean 7-point Glucose Week 24 Values Before dinner	177.8 mg/dL Standard Deviation 59.96	177.3 mg/dL Standard Deviation 56.71	156.8 mg/dL Standard Deviation 48.30
Mean 7-point Glucose Week 24 Values After dinner	180.8 mg/dL Standard Deviation 63.50	168.2 mg/dL Standard Deviation 60.77	157.8 mg/dL Standard Deviation 52.62
Mean 7-point Glucose Week 24 Values Bedtime	185.2 mg/dL Standard Deviation 62.36	185.6 mg/dL Standard Deviation 54.96	175.4 mg/dL Standard Deviation 57.37

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Full analysis set (subjects with data available at Baseline and at Week 24)

Change in body weight from Baseline to Week 24

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=132 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=140 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=153 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Change in Body Weight From Baseline to Week 24	-0.39 kg Standard Error 0.438	-0.19 kg Standard Error 0.428	0.93 kg Standard Error 0.441

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set

Efficacy as measured in proportion of subjects achieving HbA1c < or = to 7.0%

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=131 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=138 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=150 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Proportion of Responders Achieving HbA1c <= 7.0%	18.3 percentage of participants	21.7 percentage of participants	30.7 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 24

Population: Safety population

Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=173 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=171 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Incidence of Total Hypoglycemia	96.0 percentage of participants	96.0 percentage of participants	99.4 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 24

Population: Safety population

Severe Hypoglycemia defined as: Requiring 3rd party assistance.

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=173 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=171 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Incidence of Severe Hypoglycemia	18.4 percentage of participants	21.4 percentage of participants	29.2 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 24

Population: Safety population

Number of Hypoglycemic Events/Total Subject Exposure Time (in months)

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=173 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=171 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Total Hypoglycemia Event Rate	9.80 Events/Subject-Month	10.30 Events/Subject-Month	13.97 Events/Subject-Month

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 24

Population: Safety population

Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)

Outcome measures

Measure	Technosphere Insulin-Gen2 + Basal Insulin n=174 Participants Technosphere Insulin delivered via the Gen2 Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Technosphere Insulin-MedTone + Basal Insulin n=173 Participants Technosphere Insulin delivered via the MedTone C Inhaler plus subcutaneous basal insulin, doses individualized for each patient	Insulin Aspart + Basal Insulin n=171 Participants Subcutaneous insulin aspart plus subcutaneous basal insulin, doses individualized for each patient
Severe Hypoglycemia Event Rate	8.05 Events/Subject-Month	9.99 Events/Subject-Month	14.45 Events/Subject-Month

Adverse Events

Technosphere ® Insulin-Gen2 Group

Serious events: 5 serious events

Other events: 81 other events

Deaths: 0 deaths

Technosphere® Insulin With MedTone C Inhaler

Serious events: 9 serious events

Other events: 74 other events

Deaths: 0 deaths

Aspart Group

Serious events: 7 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Measure	Technosphere ® Insulin-Gen2 Group n=174 participants at risk 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	Technosphere® Insulin With MedTone C Inhaler n=173 participants at risk 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	Aspart Group n=171 participants at risk 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
General disorders Chest Discomfort	0.00% 0/174 • Baseline to Week 24 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.	0.58% 1/173 • Baseline to Week 24 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.	0.00% 0/171 • Baseline to Week 24 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.
General disorders Drowning	0.00% 0/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Infections and infestations Cytomegalovirus Infection	0.57% 1/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.00% 0/171 • Baseline to Week 24 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.
Infections and infestations Appendicitis	0.00% 0/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Injury, poisoning and procedural complications Joint Dislocation	0.57% 1/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.00% 0/171 • Baseline to Week 24 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.
Metabolism and nutrition disorders Hypoglycaemia	0.57% 1/174 • Baseline to Week 24 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.	1.2% 2/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	0.00% 0/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Nervous system disorders Hypoglycaemic Unconsciousness	0.57% 1/174 • Baseline to Week 24 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.	2.3% 4/173 • Baseline to Week 24 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.	1.2% 2/171 • Baseline to Week 24 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.
Nervous system disorders Hypoglycaemic Seizure	0.57% 1/174 • Baseline to Week 24 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.	0.58% 1/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Psychiatric disorders Mental Status Changes	0.00% 0/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Reproductive system and breast disorders Cervical Polyp	0.00% 0/174 • Baseline to Week 24 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.	0.58% 1/173 • Baseline to Week 24 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.	0.00% 0/171 • Baseline to Week 24 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.
Respiratory, thoracic and mediastinal disorders Bronchial Hyperreactivity	0.57% 1/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.00% 0/171 • Baseline to Week 24 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.

Other adverse events

Measure	Technosphere ® Insulin-Gen2 Group n=174 participants at risk 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	Technosphere® Insulin With MedTone C Inhaler n=173 participants at risk 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	Aspart Group n=171 participants at risk 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
Respiratory, thoracic and mediastinal disorders Cough	31.6% 55/174 • Baseline to Week 24 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.	22.5% 39/173 • Baseline to Week 24 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.	2.3% 4/171 • Baseline to Week 24 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.
Infections and infestations Upper Respiratory Tract Infection	8.0% 14/174 • Baseline to Week 24 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.	9.2% 16/173 • Baseline to Week 24 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.	7.0% 12/171 • Baseline to Week 24 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.
Nervous system disorders Headache	4.0% 7/174 • Baseline to Week 24 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.	2.9% 5/173 • Baseline to Week 24 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.	2.3% 4/171 • Baseline to Week 24 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.0% 7/174 • Baseline to Week 24 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.	0.00% 0/173 • Baseline to Week 24 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.	0.00% 0/171 • Baseline to Week 24 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.
Infections and infestations Bronchitis	3.4% 6/174 • Baseline to Week 24 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.	0.58% 1/173 • Baseline to Week 24 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.	2.3% 4/171 • Baseline to Week 24 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.
Infections and infestations Nasopharyngitis	2.9% 5/174 • Baseline to Week 24 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.	7.5% 13/173 • Baseline to Week 24 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.	7.0% 12/171 • Baseline to Week 24 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.
Respiratory, thoracic and mediastinal disorders Throat Irritation	2.9% 5/174 • Baseline to Week 24 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.	1.7% 3/173 • Baseline to Week 24 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.	0.58% 1/171 • Baseline to Week 24 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.
Gastrointestinal disorders Diarrhoea	2.3% 4/174 • Baseline to Week 24 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.	1.2% 2/173 • Baseline to Week 24 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.	2.9% 5/171 • Baseline to Week 24 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	1.7% 3/174 • Baseline to Week 24 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.	3.5% 6/173 • Baseline to Week 24 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.	1.8% 3/171 • Baseline to Week 24 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.
Infections and infestations Influenza	1.1% 2/174 • Baseline to Week 24 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.	5.2% 9/173 • Baseline to Week 24 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.	1.8% 3/171 • Baseline to Week 24 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.
Gastrointestinal disorders Vomiting	1.1% 2/174 • Baseline to Week 24 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.	1.7% 3/173 • Baseline to Week 24 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.	2.9% 5/171 • Baseline to Week 24 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.
Infections and infestations Urinary Tract Infection	0.57% 1/174 • Baseline to Week 24 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.	3.5% 6/173 • Baseline to Week 24 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.	1.8% 3/171 • Baseline to Week 24 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.
Gastrointestinal disorders Nausea	0.57% 1/174 • Baseline to Week 24 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.	2.9% 5/173 • Baseline to Week 24 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.	3.5% 6/171 • Baseline to Week 24 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.
Investigations Blood Creatine Phosphokinase Increase	0.00% 0/174 • Baseline to Week 24 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.	1.2% 2/173 • Baseline to Week 24 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.	2.3% 4/171 • Baseline to Week 24 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.

Additional Information

Chief Medical Officer

MannKind Corporation

Phone: 201-983-5000

Email: aboss@mannkindcorp.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER