A Phase 1, Single-center, Open-label, Randomized, Crossover Design Clinical Study in Subjects With Type 1 Diabetes Comparing Insulin Exposure & Response Following Inhalation of Technosphere Insulin Inhalation Powder Using the Gen2C Inhaler Vs Subcutaneous Rapid-Acting Analog
Overview
- Phase
- Phase 1
- Intervention
- Technosphere Insulin Inhalation Powder
- Conditions
- Type 1 Diabetes Mellitus
- Sponsor
- Mannkind Corporation
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- PK measures for TI Inhalation Powder (20U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This is an Open-label, randomized study in Type 1 diabetics looking at exposure and response (PK/PD) of TI using GEN2C Inhaler versus rapid acting analog.
Detailed Description
Subjects with Type 1 diabetes will be randomized to either one dose of TI inhaled using the Gen2C device, or one dose of subcutaneously injected Rapid Acting Analog (RAA) and crossed over. Crossover Sequences: Sequence #1: Period 1 - one 20 U cartridge of TI; Period 2 - 8 U of RAA Sequence #2: Period 1 - 8 U RAA; Period 2 - one 20 U cartridge of TI An euglycemic clamp procedure will be performed at each dosing visit. The purpose of this study is to characterize the pharmacokinetics (PK) of the one dose of TI Inhalation Powder using the Gen2C inhaler as compared to one dose of subcutaneous RAA.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women aged 18 to 60 years
- •One of more daily sc insulin injections of any insulin type or insulin pump use
- •Body mass index (BMI) = 30 kg/m2
- •Pulmonary function tests (PFTs) conducted at Visit 1:
- •FEV1 ≥ 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted
- •FVC ≥ 80% of the Third National Health and Nutrition Examination Survey (NHANES III) predicted
- •Diagnosis of type 1 diabetes for at least 12 months
- •Good venous access for blood draws
- •Written informed consent provided
- •No smoking in the previous 6 months (including cigarette, cigars, pipes) and negative urine cotinine testing (\<100 ng/mL)
Exclusion Criteria
- •Total daily insulin requirement of = 1.4 U/kg body weight
- •Serum creatinine = 2.0 mg/dL in men and \> 1.8 mg/dL in women
- •Blood donation of 500 mL within the previous 56 days
- •Current treatment with pramlintide acetate or exenatide
- •Unstable diabetes control and evidence of severe complications of diabetes (ie, autonomic neuropathy)
- •History of chronic obstructive pulmonary disease (COPD) or asthma, or any other clinically important pulmonary disease confirmed by pulmonary function testing or radiologic findings
- •Upper respiratory tract infection within 8 weeks before screening
- •History of coronary artery disease, peripheral vascular disease, or congestive heart failure
- •Allergy to study drug, food, or other study material (eg, peanuts, soy products)
- •Clinically significant active or chronic illness
Arms & Interventions
TI Inhalation Powder
Technosphere Insulin Inhalation Powder using the Gen2C inhaler
Intervention: Technosphere Insulin Inhalation Powder
RAA
Rapid Acting Analog
Intervention: Rapid Acting Analog
Outcomes
Primary Outcomes
PK measures for TI Inhalation Powder (20U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing
Time Frame: Crossover 1 time within 3 - 10 days
PK measures for RAA (8U) as measured by area under the concentration-time curve (AUC 0-360) - timepoints 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing
Time Frame: Crossover 1 time within 3 - 10 days
Secondary Outcomes
- Area under serum glucose infusion rate (GIR AUC 0-360) for TI Inhalation Powder (20U) as measured by: GIR AUC 0-360 timepoints: 0, 3, 6, 9, 12, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 240, 300 and 360 minutes post-TI dosing(Crossover 1 time within 3 - 10 days)
- Area under serum glucose infusion rate (GIR AUC 0-360) for RAA (8U) as measured by: GIR AUC 0-360 timepoints: 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 and 360 minutes post-RAA dosing(Crossover 1 time within 3 - 10 days)
- Safety variables including adverse events (AEs), clinical laboratory tests, vital signs and physical examinations(Crossover 1 time within 3 - 10 days)