Trial Outcomes & Findings for Efficacy & Safety of Inhaled Insulin in Type 1 Diabetes (NCT NCT00308308)
NCT ID: NCT00308308
Last Updated: 2014-10-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
589 participants
Primary outcome timeframe
Baseline to Week 52
Results posted on
2014-10-16
Participant Flow
First Patient enrolled Feb, 2006 Multi-national trial conducted in US, Canada, Mexico, Brazil, Argentina, Chile, Spain, UK, Poland, Russia
3 week Screening Period prior to randomization - 1420 Screened / 598 Eligible of which 589 were randomized - 822 screen failures 24 Subjects randomized but never dosed
Participant milestones
| Measure |
TI + Insulin Glargine
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
Comparator
|
|---|---|---|
|
Overall Study
STARTED
|
301
|
288
|
|
Overall Study
COMPLETED
|
198
|
220
|
|
Overall Study
NOT COMPLETED
|
103
|
68
|
Reasons for withdrawal
| Measure |
TI + Insulin Glargine
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
Comparator
|
|---|---|---|
|
Overall Study
Adverse Event
|
17
|
2
|
|
Overall Study
Lost to Follow-up
|
5
|
5
|
|
Overall Study
Physician Decision
|
15
|
7
|
|
Overall Study
Protocol Violation
|
3
|
14
|
|
Overall Study
Withdrawal by Subject
|
47
|
19
|
|
Overall Study
Various
|
7
|
5
|
|
Overall Study
Randomized but not dosed
|
8
|
16
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
Efficacy & Safety of Inhaled Insulin in Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
TI + Insulin Glargine
n=293 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 Participants
Comparator
|
Total
n=565 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.9 years
STANDARD_DEVIATION 13.06 • n=5 Participants
|
38.1 years
STANDARD_DEVIATION 13.18 • n=7 Participants
|
38 years
STANDARD_DEVIATION 13.11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
271 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
154 Participants
n=5 Participants
|
140 Participants
n=7 Participants
|
294 Participants
n=5 Participants
|
|
HbA1c
|
8.4 percent
STANDARD_DEVIATION 0.95 • n=5 Participants
|
8.5 percent
STANDARD_DEVIATION 0.97 • n=7 Participants
|
8.5 percent
STANDARD_DEVIATION 0.96 • n=5 Participants
|
|
Weight
|
76.7 kilogram
STANDARD_DEVIATION 15.64 • n=5 Participants
|
76.8 kilogram
STANDARD_DEVIATION 14.95 • n=7 Participants
|
76.7 kilogram
STANDARD_DEVIATION 15.3 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 52Population: Intention to treat (ITT) with Last Observation Carried Forward (LOCF)
Outcome measures
| Measure |
TI + Insulin Glargine
n=277 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=262 Participants
Comparator
|
|---|---|---|
|
Compare the Mean Change From Baseline to Week 52 in HbA1c
|
-0.13 Percentage
Standard Error 0.058
|
-0.37 Percentage
Standard Error 0.059
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: participants in ITT population with available data
Change from baseline in weight at Week 52
Outcome measures
| Measure |
TI + Insulin Glargine
n=186 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=206 Participants
Comparator
|
|---|---|---|
|
Change From Baseline in Weight to Week 52
|
-0.5 kilogram
Standard Error 0.32
|
1.4 kilogram
Standard Error 0.30
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: participants in ITT population with available data
Change from baseline in fasting plasma glucose at Week 52
Outcome measures
| Measure |
TI + Insulin Glargine
n=178 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=195 Participants
Comparator
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose to Week 52
|
-46.5 mg/dl
Standard Error 5.61
|
-25.7 mg/dl
Standard Error 5.23
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: participants in ITT population with available data
Number of subjects achieving week 52 HbA1c levels less than or equal to 7.0%
Outcome measures
| Measure |
TI + Insulin Glargine
n=202 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=219 Participants
Comparator
|
|---|---|---|
|
Number of Subjects Achieving Week 52 HbA1c Levels Less Than or Equal to 7.0%
|
33 Participants
|
35 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Safety population
Defined as hypoglycemic symptoms that are relieved with carbohydrate intake or blood glucose measurement \<= 63 mg/dL, regardless of symptoms.
Outcome measures
| Measure |
TI + Insulin Glargine
n=293 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 Participants
Comparator
|
|---|---|---|
|
Incidence of Total Hypoglycemia
|
85.67 percentage of participants
|
92.28 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Safety Population
Severe hypoglycemia occurs when all 3 of the following occur simultaneously: * Subject requires the assistance of another person; * Subject exhibits at least 1 cognitive neurological symptom (memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, seizure, loss of consciousness); * Measured BG is ≤ 49 mg/dL (2.7 mmol/L), or, in the absence of a BG measurement, clinical symptoms are reversed by oral carbohydrates, sc glucagon or intravenous glucose administration; OR, * Measured BG is ≤ 36 mg/dL (2.0 mmol/L) with or without symptoms.
Outcome measures
| Measure |
TI + Insulin Glargine
n=293 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 Participants
Comparator
|
|---|---|---|
|
Incidence of Severe Hypoglycemia
|
32.08 percentage of participants
|
36.40 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Safety Population
Number of Hypoglycemic Events/Total Subject Exposure Time (in months)
Outcome measures
| Measure |
TI + Insulin Glargine
n=293 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 Participants
Comparator
|
|---|---|---|
|
Total Hypoglycemia Event Rate
|
1.81 Number of events/subject-month
|
1.86 Number of events/subject-month
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Safety Population
Number of Severe Hypoglycemic Events/Total Subject Exposure Time (in months)
Outcome measures
| Measure |
TI + Insulin Glargine
n=293 Participants
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 Participants
Comparator
|
|---|---|---|
|
Severe Hypoglycemia Event Rate
|
0.08 Number of events/subject-month
|
0.10 Number of events/subject-month
|
Adverse Events
TI + Insulin Glargine
Serious events: 52 serious events
Other events: 265 other events
Deaths: 0 deaths
Insulin Aspart + Insulin Glargine
Serious events: 47 serious events
Other events: 257 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TI + Insulin Glargine
n=293 participants at risk
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 participants at risk
Comparator
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Cardiac disorders
Angina unstable
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.74%
2/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Cellulitis
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Concussion
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
1.7%
5/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.74%
2/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Hepatobiliary disorders
Hepatocellular damage
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
10.2%
30/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
12.5%
34/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Hypoglycaemic seizure
|
0.68%
2/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
1.5%
4/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
1.0%
3/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Localised infection
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Nervous system disorders
Loss of consciousness
|
2.7%
8/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
2.6%
7/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Metabolic syndrome
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Cardiac disorders
Myocardial infarction
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Pelvic abscess
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Pilonidal cyst
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Rectal abscess
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.74%
2/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Staphylococcal infection
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.37%
1/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Gastrointestinal disorders
Vomiting
|
0.34%
1/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
0.00%
0/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
Other adverse events
| Measure |
TI + Insulin Glargine
n=293 participants at risk
TI + Insulin glargine
|
Insulin Aspart + Insulin Glargine
n=272 participants at risk
Comparator
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.4%
98/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
7.7%
21/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Nervous system disorders
Headache
|
5.5%
16/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
5.5%
15/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
86.0%
252/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
92.6%
252/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Influenza
|
7.8%
23/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
7.0%
19/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Nasopharyngitis
|
12.6%
37/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
14.0%
38/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
5.5%
16/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
2.2%
6/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Investigations
Pulmonary function test decreased
|
5.5%
16/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
1.5%
4/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
|
Infections and infestations
Upper respiratory tract infection
|
15.7%
46/293 • From first dose to 30 days after last dose
Safety population is the at risk population
|
15.1%
41/272 • From first dose to 30 days after last dose
Safety population is the at risk population
|
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