Pharmacologic Response and Safety of Inhaled Insulin in Type 1 Diabetes

Phase 1

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: inhaled human insulin (INH); Drug: sc insulin lispro (LIS)

• Registration Number: NCT02713841
• Lead Sponsor: Dance Biopharm Inc.

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.

Study Timeline

• Study Start: 2013-05
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2016-03
• Study First Submitted: 2016-03-02
• Study First Submitted QC: 2016-03-15
• Last Update Submitted: 2016-03-15
• Study First Posted: 2016-03-21
• Last Update Posted: 2016-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Inhaled insulin (LOM)	inhaled human insulin (INH)	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)
Inhaled insulin (MOM1)	inhaled human insulin (INH)	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)
Inhaled insulin (MOM2)	inhaled human insulin (INH)	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)
Inhaled insulin (HOM)	inhaled human insulin (INH)	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)
subcutaneous insulin lispro (LIS)	sc insulin lispro (LIS)	single 6 unit dose of insulin lispro administered subcutaneously

Primary Outcome Measures

Name	Time	Method
Area under the insulin human / insulin lispro concentration-time curve from 0 to 8 hours (AUCINS,0-8h)	0 to 8 hours
Bioavailability	0 to 8 hours	Relative delivery efficiency (FREL) of inhaled human insulin (INH) compared to s.c. injected insulin lispro (LIS)