Type 2 Diabetes Mellitus
Conditions
Brief summary
Pharmacokinetic (PK) and Pharmacodynamic (PD) dose-response investigation of Dance-501 inhaled human insulin
Detailed description
This study investigated the pharmacokinetic (PK) and pharmacodynamic (PD) properties of Dance-501, a novel inhaled human insulin liquid formulation (INH) and device. Twenty-four subjects with type 2 diabetes (T2DM) received 3 INH doses: low (69 units), medium (139 units) and high (208 units) and 1 equivalent medium dose (18 units) of subcutaneous insulin lispro (LIS). The medium dose was repeated to determine within subject variability. PD was investigated during a 12 hour euglycemic clamp.
Interventions
DRUGINH 69 U (low)
inhaled human insulin
DRUGINH 69 U (high)
inhaled human insulin
DRUGINH 139 U
inhaled human insulin
DRUGINH 208 U
inhaled human insulin
DRUGLIS 18 U
subcutaneous insulin lispro
Sponsors
Dance Biopharm Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus treated with insulin injections at a total daily dose less than 1.2 U/kg/day. * Body mass index 25-40 kg/m2 * Hemoglobin A1c 6.5-9.5% * Forced vital capacity and forced expiratory volume in 1 second at least 75% of predicted normal values. * Fasting c-peptide less than 1 nmol/L
Exclusion criteria
* Any condition possibly affecting drug absorption from the lung, in particular subjects with decreased lung function or subjects taking bronchodilators or subjects who smoke. * Active or chronic pulmonary disease. * Any major disorder other than type 2 diabetes. * Decompensated heart failure or myocardial infarction at any time or angina pectoris within the last 12 months. * Proliferative retinopathy or maculopathy or severe neuropathy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum glucose infusion rate (GIRmax) | up to 12 hours following each dose | Assessment of the linearity of the dose-response curves |
| Area under the curve for insulin from 0-8 hours (AUCins0-8h) | 0 to 8 hours following each dose | Assessment of the linearity of the dose-response curves |
| Maximum concentration of insulin (CMaxIns) | up to 12 hours following each dose | Assessment of the linearity of the dose-response curves |
| Area under the curve for glucose infusion rate from 0-12 hours (AUGgir0-12h) | 0 to 8 hours following each dose | Assessment of the linearity of the dose-response curves |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bioavailability | 0 to 8 hours following each dose | Relative delivery efficiency (FREL) of inhaled human insulin (INH) compared to subcutaneous injected insulin lispro (LIS) |
Outcome results
None listed