Diabetes Mellitus: Type 1
Conditions
Keywords
Diabetic adult male, diabetic adult female
Brief summary
28 subjects to be enrolled for a screening period, 3 dosing visits & a follow-up visit. Visits 2 and 3 dosing of TI Inhalation Powder, cross over between two 15 U cartridges and one 30 U cartridge. Visit 4 dosing will be a sc injection of 10 IU of RAA (rapid-acting insulin analogue).
Detailed description
28 eligible subjects were planned to be enrolled to determine bioequivalence and safety parameters of two 15 U TI Inhalation Powder cartridges versus one 30 U TI Inhalation Powder cartridge, according to a randomized, 2-way crossover design. Additionally, bioavailability of one 30 U TI Inhalation Powder cartridge to a single subcutaneous injection of 10 IU of RAA will be compared.
Interventions
TI Inhalation Powder, two 15 U cartridges
DRUGTechnosphere Insulin® Inhalation Powder
TI Inhalation Powder, one 30 U cartridge
DRUGRAA Population
RAA Population: All subjects received a single 10 IU sc injection of insulin lispro.
Sponsors
Mannkind Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Males and Females \> 18 and \< 60 years of age Clinical diagnosis of type 1 diabetes mellitus with stable anti-diabetic regimen for at least 90 days prior to Screening BMI of \< 30 kg/m2 Non-smokers (never smoked or former smokers (\> 6 months since cessation) Pulmonary Function Testing (FEV1 \> 70%, FEV1/FVC \> 70%, TLC \> 80% DLco \[unc\] \> 70% of Predicted Written Informed consent
Exclusion criteria
Two or more severe hypoglycemic episodes within 6 months of Screening/Visit 1 Severe complications of diabetes Previous exposure to any inhaled insulin product other than TI inhalation Powder or similar formulation Inability to perform PFT maneuvers meeting recommended American Thoracic Society (ATS) standards of acceptability and repeatability criteria Respiratory tract infection within 8 weeks prior to Screening/Visit 1 History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease (eg. Obstructive sleep apnea), confirmed by pulmonary function testing, and/or radiologic findings Major organ system diseases including seizures, heart failure, uncontrolled hypertension, cancer within the past 5 years, liver disease, anemia or autoimmune disorder Clinically significant abnormalities on screening laboratory evaluation Female subjects who are pregnant, lactating, or planning to become pregnant during the clinical trial period or not practicing adequate birth control Unable and/or unlikely to comprehend how to use the investigational device in this study or to follow study instructions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 0 to 360 minutes post-dose | Dose-normalized baseline-corrected area under the serum insulin vs. time curve |
| 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. | 0 to 360 minutes post-dose | Maximum observed baseline-corrected serum insulin concentration |
| 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 | 0 to 360 minutes post-dose | — |
| Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro | 0 to 360 minutes post-dose | Dose-normalized baseline-corrected area under the serum insulin vs. time curve (time 0 to 360 minutes post-dose) |
Countries
United States
Participant flow
Recruitment details
This was a single site with first subject screened 24 Apr 2008
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population Any subject that received at least one treatment with TI inhalation powder | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 12.71 |
| Body mass index (BMI) | 26.61 kg/m squared STANDARD_DEVIATION 2.772 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 27 | 14 / 29 | 5 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 29 | 0 / 26 |
Outcome results
Primary
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
Dose-normalized baseline-corrected area under the serum insulin vs. time curve
Time frame: 0 to 360 minutes post-dose
Population: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Techosphere Insulin - A (2 x 15 U) | 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 |
| Techosphere Insulin - B (1 x 30 U) | 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 | 3396.6 (micro U)*min/mL | Standard Error 1.096 |
90% CI: [0.846, 1.141]
Primary
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.
Maximum observed baseline-corrected serum insulin concentration
Time frame: 0 to 360 minutes post-dose
Population: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Techosphere Insulin - A (2 x 15 U) | 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 |
| Techosphere Insulin - B (1 x 30 U) | 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. | 69.08 (micro U)/mL | Standard Error 1.098 |
90% CI: [0.823, 1.099]
Primary
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
Time frame: 0 to 360 minutes post-dose
Population: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Techosphere Insulin - A (2 x 15 U) | 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 |
| Techosphere Insulin - B (1 x 30 U) | 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 |
p-value: 0.3531Signed Rank Test
Primary
Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro
Dose-normalized baseline-corrected area under the serum insulin vs. time curve (time 0 to 360 minutes post-dose)
Time frame: 0 to 360 minutes post-dose
Population: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Techosphere Insulin - A (2 x 15 U) | 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 |
| Techosphere Insulin - B (1 x 30 U) | Relative Bioavailability of 30 U of TI (TI Inhalation Powder B) Versus 10 U of sc Insulin Lispro | 7404.0 (micro U)*min/mL | Standard Error 1.102 |
90% CI: [0.366, 0.578]