Trial Outcomes & Findings for An Open-label, Multi-center, International, Three-year, Safety and Tolerability 'Follow on' Trial (NCT NCT00754624)
NCT ID: NCT00754624
Last Updated: 2014-10-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
229 participants
Primary outcome timeframe
Baseline to 48 months
Results posted on
2014-10-16
Participant Flow
First patient enrolled May 31, 2004 Multi-center international trial conducted in USA, Bulgaria, Czech Republic, and Germany. Conducted in medical offices, hospital clinics, and universities.
This was a follow-on trial for subjects who completed one of the two parent trials (PDC-IND-0008 or MKC-TI-005). Inclusion/Exclusion was participation in these parent trials.
Participant milestones
| Measure |
TI Inhalation Powder
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Overall Study
STARTED
|
229
|
|
Overall Study
COMPLETED
|
160
|
|
Overall Study
NOT COMPLETED
|
69
|
Reasons for withdrawal
| Measure |
TI Inhalation Powder
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Overall Study
Adverse Event
|
16
|
|
Overall Study
Death
|
1
|
|
Overall Study
Physician Decision
|
8
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Withdrawal by Subject
|
28
|
|
Overall Study
Various
|
12
|
|
Overall Study
Lost to Follow-up
|
3
|
Baseline Characteristics
An Open-label, Multi-center, International, Three-year, Safety and Tolerability 'Follow on' Trial
Baseline characteristics by cohort
| Measure |
TI Inhalation Powder
n=229 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Age, Continuous
|
56.4 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
93 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
136 Participants
n=5 Participants
|
|
DLCo
|
26.16 mL/min/mmHg
STANDARD_DEVIATION 6.21 • n=5 Participants
|
|
FEV1
|
2.99 Liters
STANDARD_DEVIATION 0.70 • n=5 Participants
|
|
FPG
|
167.7 mg/dL
STANDARD_DEVIATION 42.1 • n=5 Participants
|
|
FVC
|
3.85 Liters
STANDARD_DEVIATION 0.89 • n=5 Participants
|
|
HbA1c
|
7.97 %
STANDARD_DEVIATION 1.20 • n=5 Participants
|
|
Weight
|
87.2 kg
STANDARD_DEVIATION 15.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 48 monthsPopulation: Safety Population defined as all subjects who received at least one dose of study drug
Outcome measures
| Measure |
TI Inhalation Powder
n=229 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Annual Rate of Change in FEV1 From Baseline to End of Study
|
-0.048 Liters per year
Standard Error 0.006
|
SECONDARY outcome
Timeframe: Baseline to 48 monthsPopulation: Safety
Outcome measures
| Measure |
TI Inhalation Powder
n=229 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Annual Rate of Change in FVC From Baseline to End of Study
|
-0.058 Liters per year
Standard Error 0.007
|
SECONDARY outcome
Timeframe: Baseline to 48 monthsPopulation: Safety
Outcome measures
| Measure |
TI Inhalation Powder
n=229 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Annual Rate of Change in DLCo From Baseline to End of Study
|
-0.311 mL/min/mmHg per year
Standard Error 0.073
|
SECONDARY outcome
Timeframe: Baseline to last measurement on study drug (maximum of 48 monthsPopulation: Safety
Change in HbA1c from Baseline to last measurement on study drug (maximum of 48 months)
Outcome measures
| Measure |
TI Inhalation Powder
n=225 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Change in HbA1c From Baseline to Last Measurement on Study Drug (Maximum of 48 Months)
|
0.20 percentage
Standard Deviation 1.20
|
SECONDARY outcome
Timeframe: Baseline to last study measurement on treatment (maximum of 48 months)Change from Baseline to last study measurement on treatment (maximum of 48 months)
Outcome measures
| Measure |
TI Inhalation Powder
n=225 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Change in FPG From Baseline to Last Study Measurement on Treatment (Maximum of 48 Months)
|
-5.34 milligrams per deciliter
Standard Deviation 51.43
|
SECONDARY outcome
Timeframe: Baseline to last measurement on study drug (maximum of 48 months)Population: Safety
Baseline to last measurement on study drug (maximum of 48 months)
Outcome measures
| Measure |
TI Inhalation Powder
n=229 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Change in Weight in kg From Baseline to End of Study
|
1.42 kilograms
Standard Deviation 4.41
|
SECONDARY outcome
Timeframe: End of studyPopulation: participants in Safety population with available post-baseline data
Outcome measures
| Measure |
TI Inhalation Powder
n=206 Participants
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
High Resolution Computerized Tomography Scans of the Chest
"Normal" HRCT subjects
|
47 participants
|
|
High Resolution Computerized Tomography Scans of the Chest
"Abnormal, clinically not significant" subjects
|
147 participants
|
|
High Resolution Computerized Tomography Scans of the Chest
"Abnormal, Clinically Significant" HRCT subjects
|
12 participants
|
Adverse Events
TI Inhalation Powder
Serious events: 30 serious events
Other events: 156 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TI Inhalation Powder
n=229 participants at risk
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Coronary artery disease
|
1.3%
3/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Myocardial ischaemia
|
0.87%
2/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Acute myocardial infarction
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Angina pectoris
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Atrioventricular block complete
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Cardiac failure
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Cardiovascular disorder
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Cardiac disorders
Myocardial infarction
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Eye disorders
Cataract
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Appendicitis
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Gastroenteritis
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Sinusitis
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Injury, poisoning and procedural complications
Device failure
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Metabolism and nutrition disorders
Hypoglycaemic seizure
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Musculoskeletal and connective tissue disorders
Localised osteoarthritis
|
0.87%
2/229 • May 31, 2004 to June 5, 2008
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma stage unspecified
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Nervous system disorders
Ataxia
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Nervous system disorders
Diabetic neuropathy
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Nervous system disorders
Dizziness
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Nervous system disorders
Syncope
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Nervous system disorders
Vertebrobasilar insufficiency
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Renal and urinary disorders
Calculus ureteric
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Renal and urinary disorders
Renal failure acute
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Vascular disorders
Aortic aneurysm
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Vascular disorders
Arterial stenosis
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Vascular disorders
Deep vein thrombosis
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
|
Vascular disorders
Hypertension
|
0.44%
1/229 • May 31, 2004 to June 5, 2008
|
Other adverse events
| Measure |
TI Inhalation Powder
n=229 participants at risk
Technosphere® Insulin Inhalation Powder
|
|---|---|
|
Eye disorders
Cataract
|
5.2%
12/229 • May 31, 2004 to June 5, 2008
|
|
Eye disorders
Diabetic retinopathy
|
5.7%
13/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Upper respiratory tract infection
|
17.5%
40/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Nasopharyngitis
|
14.0%
32/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Sinusitis
|
5.7%
13/229 • May 31, 2004 to June 5, 2008
|
|
Infections and infestations
Bronchitis
|
5.2%
12/229 • May 31, 2004 to June 5, 2008
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
41.0%
94/229 • May 31, 2004 to June 5, 2008
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
7.4%
17/229 • May 31, 2004 to June 5, 2008
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
5.7%
13/229 • May 31, 2004 to June 5, 2008
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.3%
19/229 • May 31, 2004 to June 5, 2008
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.9%
18/229 • May 31, 2004 to June 5, 2008
|
|
Nervous system disorders
Headache
|
6.1%
14/229 • May 31, 2004 to June 5, 2008
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.5%
40/229 • May 31, 2004 to June 5, 2008
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
10.9%
25/229 • May 31, 2004 to June 5, 2008
|
|
Vascular disorders
Hypertension
|
6.6%
15/229 • May 31, 2004 to June 5, 2008
|
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