Pharmacologic Response and Safety of Inhaled Insulin in Type 1 Diabetes

NCT ID: NCT02713841

Last Updated: 2016-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2013-07-31

Brief Summary

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.

Detailed 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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Inhaled insulin (LOM)

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)

Group Type: EXPERIMENTAL

inhaled human insulin (INH)

Intervention Type: DRUG

recombinant human insulin administered with Adagio-01 inhaler device

Inhaled insulin (MOM1)

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)

Group Type: EXPERIMENTAL

inhaled human insulin (INH)

Intervention Type: DRUG

recombinant human insulin administered with Adagio-01 inhaler device

Inhaled insulin (MOM2)

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)

Group Type: EXPERIMENTAL

inhaled human insulin (INH)

Intervention Type: DRUG

recombinant human insulin administered with Adagio-01 inhaler device

Inhaled insulin (HOM)

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)

Group Type: EXPERIMENTAL

inhaled human insulin (INH)

Intervention Type: DRUG

recombinant human insulin administered with Adagio-01 inhaler device

subcutaneous insulin lispro (LIS)

single 6 unit dose of insulin lispro administered subcutaneously

Group Type: ACTIVE_COMPARATOR

sc insulin lispro (LIS)

Intervention Type: DRUG

insulin lispro administered subcutaneously

Interventions

inhaled human insulin (INH)

recombinant human insulin administered with Adagio-01 inhaler device

Intervention Type: DRUG

sc insulin lispro (LIS)

insulin lispro administered subcutaneously

Intervention Type: DRUG

Other Intervention Names

Dance-501

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dance Biopharm Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Heise, MD

Role: PRINCIPAL_INVESTIGATOR

Profil Institut für Stoffwechselforschung GmbH

Other Identifiers

Samba-01

Identifier Type: -

Identifier Source: org_study_id