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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1: TI Inhalation Powder A | Experimental | Technosphere® Insulin Inhalation Powder, two 15 U cartridges |
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| 2: TI Inhalation Powder B | Experimental | Technosphere® Insulin Inhalation Powder, one 30 U cartridge |
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| 3: RAA Population | Experimental | Rapid Acting Analogue subjects received 10 IU sc Insulin Lispro |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Technosphere® Insulin Inhalation Powder | Drug | TI Inhalation Powder, two 15 U cartridges |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | 0 to 360 minutes post-dose |
| 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 | 0 to 360 minutes post-dose |
| 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 | Dose-normalized baseline-corrected area under the serum insulin vs. time curve (time 0 to 360 minutes post-dose) | 0 to 360 minutes post-dose |
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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
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institute for Clinical Research Inc. | Chula Vista | California | 91911 | United States | ||
| Diabetes & Glandular Disease Research Assoc PA |
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.
This was a single site with first subject screened 24 Apr 2008
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| TI Dosing Period 1 (1 Day) |
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| Technosphere Insulin® Inhalation Powder | Drug | TI Inhalation Powder, one 30 U cartridge |
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| RAA Population | Drug | RAA Population: All subjects received a single 10 IU sc injection of insulin lispro. |
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| San Antonio |
| Texas |
| 78229 |
| United States |
| FG001 |
| 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 |
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| NOT COMPLETED |
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| Washout 1 (3 - 14 Days) |
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| TI Dosing Period 2 (1 Day) |
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| Washout 2 (3 - 14 Days) |
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| Lispro Dosing Period (1 Day) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Safety Population | Any subject that received at least one treatment with TI inhalation powder |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Body mass index (BMI) | Mean | Standard Deviation | kg/m squared |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 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). | Posted | Least Squares Mean | Standard Error | (micro U)*min/mL | 0 to 360 minutes post-dose |
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| 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 | 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). | Posted | Least Squares Mean | Standard Error | (micro U)/mL | 0 to 360 minutes post-dose |
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| 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 | 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). | Posted | Median | Full Range | min | 0 to 360 minutes post-dose |
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| 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) | 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). | Posted | Least Squares Mean | Standard Error | (micro U)*min/mL | 0 to 360 minutes post-dose |
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From time of first dose to 30d after last dose; Serious adverse event (SAE) = until resolution
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Techosphere Insulin - A (2 x 15 U) | 30 U of Technosphere Insulin (TI) administered as 2 x 15 U cartridges as a single-dose during a glucose clamp procedure | 0 | 27 | 9 | 27 | ||
| EG001 | Techosphere Insulin - B (1 x 30 U) | 30 U of Technosphere Insulin (TI) administered as 1 x 30 U cartridges as a single-dose during a glucose clamp procedure | 0 | 29 | 14 | 29 | ||
| EG002 | 10 U Subcutaneous (sc) Insulin Lispro | 10 U of insulin lispro administered subcutaneously during a glucose clamp procedure | 0 | 26 | 5 | 26 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 7.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 7.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 7.1 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 7.1 | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA 7.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | MannKind Corporation | 201-983-5000 | aboss@mannkindcorp.com |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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