Pharmacokinetic (PK) and Pharmacodynamic (PD) dose-response investigation of Dance-501 inhaled human insulin

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.

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.