Pharmacologic Response and Safety of Inhaled Insulin in Type 1 Diabetes (Samba-01)

Dance Biopharm

Status and phase: Completed; Phase 2; Phase 1

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: sc insulin lispro (LIS); Drug: inhaled human insulin (INH)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02713841

Samba-01

Details and patient eligibility

About

The purpose of this study was to compare the pharmacokinetic (PK) response after inhaled insulin administration with 3 different inhalation regimens and with subcutaneous insulin administration.

Full description

This first-in-human trial investigated the optimal particle size for absorption of Dance-501, an aerosolized liquid human insulin for inhalation (INH).

Twelve subjects with type 1 diabetes received an INH dose (50 IU) using an inhaler on 4 visits and 6 U insulin lispro (LIS) sc on a separate visit to assess relative bioavailability (FREL) of INH. The inhaler was configured to generate insulin aerosol particles sized 3.5-4.0 μm (low output mesh; LOM), 4.3-4.8 μm (medium output mesh; MOM) or 5.0-5.5 μm (high output mesh; HOM) during low inspiratory flow. To assess within subject variability, MOM was used twice. Pharmacokinetics (PK) were measured up to 8 hours after dosing.

Enrollment: 12 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 1 diabetes mellitus treated with multiple daily insulin injections or continuous subcutaneous insulin infusion and total daily insulin dose less than 1.2 units/kg/day.
• Body mass index 18.0 - 28.0 kg/m2.
• Hemoglobin A1c less than or equal to 9%.
• Forced vital capacity and forced expiratory volume in one second at least 75% of predicted normal values for race, age, gender and height.
• Fasting C-peptide less than 0.3 nmol/L.

Exclusion criteria

• Subjects with 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 clinically significant major disorders other than diabetes mellitus.
• Decompensated heart failure at any time or angina pectoris within the last 12 months or acute myocardial infarction at any time.
• Proliferative retinopathy or severe neuropathy.

Trial design

12 participants in 5 patient groups

Inhaled insulin (LOM)

Experimental group

Description:

single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a low output mesh (aerosol particles sized 3.5-4.0 μm)

Treatment:

Drug: inhaled human insulin (INH)

Inhaled insulin (MOM1)

Experimental group

Description:

single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a medium output mesh (aerosol particles sized 4.3-4.8 μm)

Treatment:

Drug: inhaled human insulin (INH)

Inhaled insulin (MOM2)

Experimental group

Description:

repeat of single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a medium output mesh (aerosol particles sized 4.3-4.8 μm)

Treatment:

Drug: inhaled human insulin (INH)

Inhaled insulin (HOM)

Experimental group

Description:

single 50 unit dose of Dance inhaled insulin administered using the Adagio-01 inhaler device with a high output mesh (aerosol particles sized 5.0-5.5 μm)

Treatment:

Drug: inhaled human insulin (INH)

subcutaneous insulin lispro (LIS)

Active Comparator group

Description:

single 6 unit dose of insulin lispro administered subcutaneously

Treatment:

Drug: sc insulin lispro (LIS)