Pharmacologic Response and Safety of Inhaled Insulin in Type 1 Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Samba-01: A Phase 1/2 Trial Investigating the Pharmacokinetics, Pharmacodynamics and Safety of Inhaled Insulin in Subjects With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: inhaled human insulin (INH)
* Drug: sc insulin lispro (LIS)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled insulin (LOM)<br>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) | Drug: inhaled human insulin (INH)<br>* recombinant human insulin administered with Adagio-01 inhaler device<br>* Other names: Dance-501;|
| Experimental: Inhaled insulin (MOM1)<br>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) | Drug: inhaled human insulin (INH)<br>* recombinant human insulin administered with Adagio-01 inhaler device<br>* Other names: Dance-501;|
| Experimental: Inhaled insulin (MOM2)<br>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) | Drug: inhaled human insulin (INH)<br>* recombinant human insulin administered with Adagio-01 inhaler device<br>* Other names: Dance-501;|
| Experimental: Inhaled insulin (HOM)<br>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) | Drug: inhaled human insulin (INH)<br>* recombinant human insulin administered with Adagio-01 inhaler device<br>* Other names: Dance-501;|
| Active Comparator: subcutaneous insulin lispro (LIS)<br>single 6 unit dose of insulin lispro administered subcutaneously | Drug: sc insulin lispro (LIS)<br>* insulin lispro administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

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