Trial Outcomes & Findings for Safety of Inhaled Insulin With Type 1 and Type 2 Diabetes (NCT NCT00308737)
NCT ID: NCT00308737
Last Updated: 2014-10-16
Results Overview
Change from Baseline to End of Study in FEV1 by MMRM
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
2053 participants
Primary outcome timeframe
Baseline to Month 24
Results posted on
2014-10-16
Participant Flow
First subject enrolled July 25, 2005 Multi-national trial conducted in Canada, Czech Republic, Poland, Russia, Spain, Ukraine, UK, and US
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
Participant milestones
| Measure |
Technosphere® Insulin
Technosphere Insulin with or without basal insulin, or oral anti-diabetic medications, or any combination of the previous.
|
Usual Care
Usual care may consist of oral anti-diabetic medications, basal insulin, subcutaneous prandial insulin, or any combination of the previous.
|
Non-diabetes
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Overall Study
STARTED
|
938
|
951
|
164
|
|
Overall Study
COMPLETED
|
475
|
662
|
127
|
|
Overall Study
NOT COMPLETED
|
463
|
289
|
37
|
Reasons for withdrawal
| Measure |
Technosphere® Insulin
Technosphere Insulin with or without basal insulin, or oral anti-diabetic medications, or any combination of the previous.
|
Usual Care
Usual care may consist of oral anti-diabetic medications, basal insulin, subcutaneous prandial insulin, or any combination of the previous.
|
Non-diabetes
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Overall Study
Various
|
32
|
20
|
8
|
|
Overall Study
Adverse Event
|
104
|
9
|
0
|
|
Overall Study
Death
|
4
|
3
|
0
|
|
Overall Study
Lost to Follow-up
|
56
|
80
|
5
|
|
Overall Study
Physician Decision
|
15
|
2
|
1
|
|
Overall Study
Protocol Violation
|
34
|
9
|
5
|
|
Overall Study
Withdrawal by Subject
|
218
|
166
|
18
|
Baseline Characteristics
Safety of Inhaled Insulin With Type 1 and Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Technosphere® Insulin
n=923 Participants
Technosphere Insulin
|
Usual Care
n=949 Participants
Usual care
|
Non-diabetes
n=163 Participants
Subjects without abnormalities in glucose control
|
Total
n=2035 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
50.8 years
STANDARD_DEVIATION 11.55 • n=5 Participants
|
50.4 years
STANDARD_DEVIATION 11.62 • n=7 Participants
|
38.2 years
STANDARD_DEVIATION 12.59 • n=5 Participants
|
49.6 years
STANDARD_DEVIATION 12.15 • n=4 Participants
|
|
Sex: Female, Male
Female
|
366 Participants
n=5 Participants
|
371 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
829 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
557 Participants
n=5 Participants
|
578 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
1206 Participants
n=4 Participants
|
|
Body mass index
|
29.87 kilograms per meter squared
STANDARD_DEVIATION 5.366 • n=5 Participants
|
29.76 kilograms per meter squared
STANDARD_DEVIATION 5.035 • n=7 Participants
|
25.27 kilograms per meter squared
STANDARD_DEVIATION 4.494 • n=5 Participants
|
29.5 kilograms per meter squared
STANDARD_DEVIATION 5.29 • n=4 Participants
|
|
HbA1c
|
8.7 percentage
STANDARD_DEVIATION 1.39 • n=5 Participants
|
8.7 percentage
STANDARD_DEVIATION 1.38 • n=7 Participants
|
0 percentage
STANDARD_DEVIATION 0 • n=5 Participants
|
8.4 percentage
STANDARD_DEVIATION 1.61 • n=4 Participants
|
|
Weight
|
87.69 kilograms
STANDARD_DEVIATION 18.628 • n=5 Participants
|
87.53 kilograms
STANDARD_DEVIATION 17.638 • n=7 Participants
|
74.35 kilograms
STANDARD_DEVIATION 16.204 • n=5 Participants
|
86.6 kilograms
STANDARD_DEVIATION 18.33 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Month 24Population: Intention to Treat (ITT)
Change from Baseline to End of Study in FEV1 by MMRM
Outcome measures
| Measure |
Technosphere® Insulin
n=730 Participants
Technosphere Insulin
|
Usual Care
n=824 Participants
Usual care
|
Non-diabetes
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change From Baseline to Month 24 in Forced Expiratory Volume in 1 Second (FEV1) by MMRM for TI vs Usual Care
|
-0.16 liters
Standard Deviation 0.208
|
-0.12 liters
Standard Deviation 0.211
|
—
|
PRIMARY outcome
Timeframe: Baseline to Month 24Population: Intention to Treat (ITT)
FEV1 decrease of ≥ 15% from Baseline value at last measurement
Outcome measures
| Measure |
Technosphere® Insulin
n=730 Participants
Technosphere Insulin
|
Usual Care
n=824 Participants
Usual care
|
Non-diabetes
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
FEV1 Decrease of ≥ 15% From Baseline Value at Last Measurement for TI vs Usual Care
|
42 Participants
|
27 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: Intention to Treat (ITT) with Last Observation Carried Forward (LOCF)
Change from Baseline to last measurement(Month 24) in FEV1
Outcome measures
| Measure |
Technosphere® Insulin
n=730 Participants
Technosphere Insulin
|
Usual Care
n=824 Participants
Usual care
|
Non-diabetes
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change From Baseline to Last Measurement in FEV1 for TI vs Usual Care
|
-0.128 liters
Interval -0.144 to -0.113
|
-0.092 liters
Interval -0.107 to -0.077
|
—
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: Intention to Treat (ITT)
Change from Baseline to Month 24 in FVC by MMRM
Outcome measures
| Measure |
Technosphere® Insulin
n=730 Participants
Technosphere Insulin
|
Usual Care
n=824 Participants
Usual care
|
Non-diabetes
n=145 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change From Baseline to Month 24 in Forced Vital Capacity (FVC) by MMRM
|
-0.14 liters
Standard Deviation 0.242
|
-0.11 liters
Standard Deviation 0.262
|
-0.09 liters
Standard Deviation 0.210
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: participants in ITT population with available data
Change from baseline to Month 24 in TLC by MMRM
Outcome measures
| Measure |
Technosphere® Insulin
n=717 Participants
Technosphere Insulin
|
Usual Care
n=817 Participants
Usual care
|
Non-diabetes
n=144 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change From Baseline to Month 24 in Total Lung Capacity (TLC) by MMRM
|
-0.05 liters
Standard Deviation 0.321
|
-0.07 liters
Standard Deviation 0.322
|
-0.02 liters
Standard Deviation 0.297
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: participants in ITT population with available data
Change from baseline to Month 24 in hemoglobin-corrected DLco by MMRM
Outcome measures
| Measure |
Technosphere® Insulin
n=723 Participants
Technosphere Insulin
|
Usual Care
n=818 Participants
Usual care
|
Non-diabetes
n=144 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change From Baseline to Month 24 in Hemoglobin Corrected DLco by MMRM
|
-1.60 mL/min/mmHg
Standard Deviation 2.830
|
-1.36 mL/min/mmHg
Standard Deviation 2.862
|
-1.33 mL/min/mmHg
Standard Deviation 3.203
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: participants in ITT population with available data
FVC Decrease of ≥15% from Baseline Value at Last Measurement
Outcome measures
| Measure |
Technosphere® Insulin
n=730 Participants
Technosphere Insulin
|
Usual Care
n=824 Participants
Usual care
|
Non-diabetes
n=145 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Forced Vital Capacity (FVC) Decrease of ≥ 15% From Baseline Value at Last Measurement
|
23 participants
|
17 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: participants in ITT population with available data
TLC Decrease of ≥ 15% from Baseline Value at Last Measurement
Outcome measures
| Measure |
Technosphere® Insulin
n=717 Participants
Technosphere Insulin
|
Usual Care
n=817 Participants
Usual care
|
Non-diabetes
n=144 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Total Lung Capacity (TLC) Decrease of ≥ 15% From Baseline Value at Last Measurement
|
7 Participants
|
6 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: participants in ITT population with available data
Hemoglobin-corrected DLco decrease of ≥ 15% from baseline value at last measurement
Outcome measures
| Measure |
Technosphere® Insulin
n=723 Participants
Technosphere Insulin
|
Usual Care
n=818 Participants
Usual care
|
Non-diabetes
n=144 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Hemoglobin-Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Decrease of ≥ 15% From Baseline Value at Last Measurement
|
105 Participants
|
108 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: participants in ITT population with available data
Hemoglobin-corrected DLco decrease of \>3 ml/min/mmHg from baseline value at last measurement
Outcome measures
| Measure |
Technosphere® Insulin
n=723 Participants
Technosphere Insulin
|
Usual Care
n=818 Participants
Usual care
|
Non-diabetes
n=144 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Hemoglobin-Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLco) Decrease of >3 ml/Min/mmHg From Baseline Value at Last Measurement
|
181 Participants
|
181 Participants
|
40 Participants
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: Intention to treat (ITT) with last observation carried forward (LOCF)
Change from baseline in HbA1c at last measurement
Outcome measures
| Measure |
Technosphere® Insulin
n=725 Participants
Technosphere Insulin
|
Usual Care
n=818 Participants
Usual care
|
Non-diabetes
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Last Measurement for TI vs Usual Care
|
-0.42 percentage
Standard Deviation 1.410
|
-0.49 percentage
Standard Deviation 1.37
|
—
|
SECONDARY outcome
Timeframe: Baseline to Month 24Population: Safety population at Month 24
Change from baseline in weight at Month 24
Outcome measures
| Measure |
Technosphere® Insulin
n=185 Participants
Technosphere Insulin
|
Usual Care
n=664 Participants
Usual care
|
Non-diabetes
n=126 Participants
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Change in Weight From Baseline at Month 24
|
1.0 kilograms
Standard Deviation 6.653
|
1.64 kilograms
Standard Deviation 5.066
|
1.19 kilograms
Standard Deviation 4.457
|
Adverse Events
Technosphere® Insulin
Serious events: 92 serious events
Other events: 559 other events
Deaths: 0 deaths
Usual Care
Serious events: 91 serious events
Other events: 472 other events
Deaths: 0 deaths
Non-diabetes
Serious events: 5 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Technosphere® Insulin
n=923 participants at risk
Technosphere Insulin
|
Usual Care
n=949 participants at risk
Usual care (taking insulin)
|
Non-diabetes
n=163 participants at risk
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Localised osteoarthritis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Blood and lymphatic system disorders
Thrombocythaemia
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Blood and lymphatic system disorders
Pernicious anaemia
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Coronary artery disease
|
0.54%
5/923 • 24 months
|
0.32%
3/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Myocardial infarction
|
0.22%
2/923 • 24 months
|
0.42%
4/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Angina unstable
|
0.11%
1/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Cardiac arrest
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Coronary artery atherosclerosis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Coronary artery occlusion
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Coronary artery stenosis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Myocardial ischaemia
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Acute myocardial infarction
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Aortic valve stenosis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Cardiac failure
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Cardiac failure chronic
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Cardiac failure congestive
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Ear and labyrinth disorders
Meniere's disease
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Eye disorders
Retinal detachment
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Eye disorders
Retinal disorder
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Eye disorders
Eye haemorrhage
|
0.00%
0/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Eye disorders
Glaucoma
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.33%
3/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Gastritis
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Anal fistula
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Erosive oesophagitis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Pancreatic cyst
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Benign colonic polyp
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Gastroduodenitis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Pancreatic necrosis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Pancreatitis chronic
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Peritonitis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
General disorders
Chest pain
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
General disorders
Generalised oedema
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.22%
2/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Hepatitis toxic
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Hepatobiliary disorders
Gallbladder disorder
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Pneumonia
|
0.22%
2/923 • 24 months
|
0.42%
4/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Diabetic gangrene
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Appendicitis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.61%
1/163 • 24 months
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Urinary tract infection
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Carbuncle
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Cellulitis streptococcal
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Diverticulitis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Furuncle
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Injection site cellulitis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Otitis media acute
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Parotitis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Perirectal abscess
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Pyelonephritis chronic
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Rectal abscess
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Wound infection
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Cellulitis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.61%
1/163 • 24 months
|
|
Infections and infestations
Arthritis bacterial
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Gangrene
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Postoperative infection
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Staphylococcal scalded skin syndrome
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Infections and infestations
Chronic tonsillitis
|
0.00%
0/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.61%
1/163 • 24 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.11%
1/923 • 24 months
|
0.32%
3/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Overdose
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Cerebral haemorrhage traumatic
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Investigations
Blood potassium increased
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.98%
9/923 • 24 months
|
1.1%
10/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.54%
5/923 • 24 months
|
0.42%
4/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.22%
2/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.11%
1/923 • 24 months
|
0.63%
6/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Hypoglycaemic seizure
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Ketosis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Metabolism and nutrition disorders
Diabetic complication
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/923 • 24 months
|
0.32%
3/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Spondylosis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis
|
0.00%
0/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.61%
1/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.22%
2/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign salivary gland neoplasm
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian epithelial cancer
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour
|
0.00%
0/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.61%
1/163 • 24 months
|
|
Nervous system disorders
Loss of consciousness
|
0.54%
5/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.11%
1/923 • 24 months
|
0.42%
4/949 • 24 months
|
0.61%
1/163 • 24 months
|
|
Nervous system disorders
Ischaemic stroke
|
0.11%
1/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Carotid artery stenosis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Convulsion
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Epilepsy
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Multiple sclerosis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Transient ischaemic attack
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Hypoglycaemic coma
|
0.00%
0/923 • 24 months
|
0.21%
2/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Radiculitis lumbosacral
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Nervous system disorders
Sciatica
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Psychiatric disorders
Depression
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Renal and urinary disorders
Hydronephrosis
|
0.22%
2/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.11%
1/923 • 24 months
|
0.32%
3/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Renal and urinary disorders
Renal failure acute
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.22%
2/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Reproductive system and breast disorders
Adenomyosis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnoea
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Vocal cord polyp
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Vascular disorders
Aortic stenosis
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Vascular disorders
Circulatory collapse
|
0.11%
1/923 • 24 months
|
0.00%
0/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Vascular disorders
Atherosclerosis obliterans
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Vascular disorders
Extremity necrosis
|
0.00%
0/923 • 24 months
|
0.11%
1/949 • 24 months
|
0.00%
0/163 • 24 months
|
Other adverse events
| Measure |
Technosphere® Insulin
n=923 participants at risk
Technosphere Insulin
|
Usual Care
n=949 participants at risk
Usual care (taking insulin)
|
Non-diabetes
n=163 participants at risk
Subjects without abnormalities in glucose control
|
|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
12.9%
119/923 • 24 months
|
15.1%
143/949 • 24 months
|
21.5%
35/163 • 24 months
|
|
Infections and infestations
Nasopharyngitis
|
7.3%
67/923 • 24 months
|
7.3%
69/949 • 24 months
|
8.6%
14/163 • 24 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
39.5%
365/923 • 24 months
|
39.0%
370/949 • 24 months
|
0.00%
0/163 • 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.8%
257/923 • 24 months
|
4.4%
42/949 • 24 months
|
3.1%
5/163 • 24 months
|
Additional Information
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