Trial Outcomes & Findings for A Study Designed to Compare 2 Dose Strengths of TI Inhalation Powder in Adults With Type 1 Diabetes Mellitus and to Compare One of Those Formulations (30Units) With an Injection of Insulin Lispro (NCT NCT00662857)
NCT ID: NCT00662857
Last Updated: 2014-10-16
Results Overview
Dose-normalized baseline-corrected area under the serum insulin vs. time curve
COMPLETED
PHASE2
29 participants
0 to 360 minutes post-dose
2014-10-16
Participant Flow
This was a single site with first subject screened 24 Apr 2008
Subjects assigned at Visit 2 to either: 2 15 U cartridges (TI Inhalation Powder A) or 1 30 U cartridge (TI Inhalation Powder B). At Visit 3 each subject was crossed over to the other treatment group. At Visit 4 subjects received a single sc injection of 10 IU of insulin lispro to 1 of 3 possible injection sites: arm, leg, or abdomen.
Participant milestones
| Measure |
TI - A (2x15 U)/TI - B (1x30 U)/10 U sc Insulin Lispro
Treatment sequence: 30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose, followed by 30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose, and then 10 U of insulin lispro administered subcutaneously (sc) during a glucose clamp procedure
|
TI - B (1x30 U)/TI - A (2x15 U)/10 U sc Insulin Lispro
Treatment sequence: 30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose, followed by 30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose, and then 10 U of insulin lispro administered subcutaneously (sc) during a glucose clamp procedure
|
|---|---|---|
|
TI Dosing Period 1 (1 Day)
STARTED
|
13
|
16
|
|
TI Dosing Period 1 (1 Day)
COMPLETED
|
13
|
16
|
|
TI Dosing Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
|
Washout 1 (3 - 14 Days)
STARTED
|
13
|
16
|
|
Washout 1 (3 - 14 Days)
COMPLETED
|
13
|
14
|
|
Washout 1 (3 - 14 Days)
NOT COMPLETED
|
0
|
2
|
|
TI Dosing Period 2 (1 Day)
STARTED
|
13
|
14
|
|
TI Dosing Period 2 (1 Day)
COMPLETED
|
13
|
14
|
|
TI Dosing Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
|
Washout 2 (3 - 14 Days)
STARTED
|
13
|
14
|
|
Washout 2 (3 - 14 Days)
COMPLETED
|
12
|
14
|
|
Washout 2 (3 - 14 Days)
NOT COMPLETED
|
1
|
0
|
|
Lispro Dosing Period (1 Day)
STARTED
|
12
|
14
|
|
Lispro Dosing Period (1 Day)
COMPLETED
|
12
|
14
|
|
Lispro Dosing Period (1 Day)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
TI - A (2x15 U)/TI - B (1x30 U)/10 U sc Insulin Lispro
Treatment sequence: 30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose, followed by 30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose, and then 10 U of insulin lispro administered subcutaneously (sc) during a glucose clamp procedure
|
TI - B (1x30 U)/TI - A (2x15 U)/10 U sc Insulin Lispro
Treatment sequence: 30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose, followed by 30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose, and then 10 U of insulin lispro administered subcutaneously (sc) during a glucose clamp procedure
|
|---|---|---|
|
Washout 1 (3 - 14 Days)
Physician Decision
|
0
|
1
|
|
Washout 1 (3 - 14 Days)
Withdrawal by Subject
|
0
|
1
|
|
Washout 2 (3 - 14 Days)
Cannot Use Clamp Data
|
1
|
0
|
Baseline Characteristics
A Study Designed to Compare 2 Dose Strengths of TI Inhalation Powder in Adults With Type 1 Diabetes Mellitus and to Compare One of Those Formulations (30Units) With an Injection of Insulin Lispro
Baseline characteristics by cohort
| Measure |
Safety Population
n=29 Participants
Any subject that received at least one treatment with TI inhalation powder
|
|---|---|
|
Age, Continuous
|
37.4 years
STANDARD_DEVIATION 12.71 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Body mass index (BMI)
|
26.61 kg/m squared
STANDARD_DEVIATION 2.772 • n=5 Participants
|
PRIMARY outcome
Timeframe: 0 to 360 minutes post-dosePopulation: Per Protocol Population - All subjects who completed the crossover portion of the trial (through Visit 3), had serum insulin concentration data for both TI Inhalation Powder A and TI Inhalation Powder B and were deemed to be protocol compliant (no major protocol violations during the clinical trial).
Dose-normalized baseline-corrected area under the serum insulin vs. time curve
Outcome measures
| Measure |
Techosphere Insulin - A (2 x 15 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose during a glucose clamp procedure
|
Techosphere Insulin - B (1 x 30 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose during a glucose clamp procedure
|
|---|---|---|
|
Bioequivalence of Two 15 U Cartridges (TI Inhalation Powder A) and One 30 U Cartridge (TI Inhalation Powder B) Based on Baseline Corrected Insulin AUC0-360
|
3337.2 (micro U)*min/mL
Standard Error 1.096
|
3396.6 (micro U)*min/mL
Standard Error 1.096
|
PRIMARY outcome
Timeframe: 0 to 360 minutes post-dosePopulation: Per Protocol Population - All subjects who completed the crossover portion of the trial (through Visit 3), had serum insulin concentration data for both TI Inhalation Powder A and TI Inhalation Powder B and were deemed to be protocol compliant (no major protocol violations during the clinical trial).
Maximum observed baseline-corrected serum insulin concentration
Outcome measures
| Measure |
Techosphere Insulin - A (2 x 15 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose during a glucose clamp procedure
|
Techosphere Insulin - B (1 x 30 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose during a glucose clamp procedure
|
|---|---|---|
|
Bioequivalence of Two 15 U Cartridges (TI Inhalation Powder A) and One 30 U Cartridge (TI Inhalation Powder B) Based on Baseline Corrected Insulin Cmax.
|
65.72 (micro U)/mL
Standard Error 1.098 • Interval 0.823 to 1.099
|
69.08 (micro U)/mL
Standard Error 1.098
|
PRIMARY outcome
Timeframe: 0 to 360 minutes post-dosePopulation: Per Protocol Population - All subjects who completed the crossover portion of the trial (through Visit 3), had serum insulin concentration data for both TI Inhalation Powder A and TI Inhalation Powder B and were deemed to be protocol compliant (no major protocol violations during the clinical trial).
Outcome measures
| Measure |
Techosphere Insulin - A (2 x 15 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose during a glucose clamp procedure
|
Techosphere Insulin - B (1 x 30 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose during a glucose clamp procedure
|
|---|---|---|
|
Bioequivalence of Two 15 U Cartridges (TI Inhalation Powder A) and One 30 U Cartridge (TI Inhalation Powder B) Based on Baseline Corrected Insulin Tmax
|
10 min
Interval 5.0 to 24.0
|
10 min
Interval 5.0 to 20.0
|
PRIMARY outcome
Timeframe: 0 to 360 minutes post-dosePopulation: Rapid-acting insulin Analogue (RAA) Population All subjects who had serum insulin concentration data for both TI Inhalation Powder B and insulin lispro and were deemed to be protocol compliant (no major protocol violations during the clinical trial).
Dose-normalized baseline-corrected area under the serum insulin vs. time curve (time 0 to 360 minutes post-dose)
Outcome measures
| Measure |
Techosphere Insulin - A (2 x 15 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose during a glucose clamp procedure
|
Techosphere Insulin - B (1 x 30 U)
n=25 Participants
30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose during a glucose clamp procedure
|
|---|---|---|
|
Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro
|
3406.8 (micro U)*min/mL
Standard Error 1.095
|
7404.0 (micro U)*min/mL
Standard Error 1.102
|
Adverse Events
Techosphere Insulin - A (2 x 15 U)
Techosphere Insulin - B (1 x 30 U)
10 U Subcutaneous (sc) Insulin Lispro
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Techosphere Insulin - A (2 x 15 U)
n=27 participants at risk
30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose during a glucose clamp procedure
|
Techosphere Insulin - B (1 x 30 U)
n=29 participants at risk
30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose during a glucose clamp procedure
|
10 U Subcutaneous (sc) Insulin Lispro
n=26 participants at risk
10 U of insulin lispro administered subcutaneously during a glucose clamp procedure
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.8%
4/27 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
24.1%
7/29 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
0.00%
0/26 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
|
Nervous system disorders
Headache
|
7.4%
2/27 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
17.2%
5/29 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
3.8%
1/26 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
|
Gastrointestinal disorders
Nausea
|
7.4%
2/27 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
3.4%
1/29 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
3.8%
1/26 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
3.7%
1/27 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
13.8%
4/29 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
3.8%
1/26 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/27 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
0.00%
0/29 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
7.7%
2/26 • From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
|
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