Dose-Response and Variability of Inhaled Insulin in Type 2 Diabetes

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

Detailed Description
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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.

Official Title
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Samba-02: An Investigation of the Dose-Response and Subject Variability of Inhaled Insulin in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: INH 69 U (low)
* Drug: INH 69 U (high)
* Drug: INH 139 U
* Drug: INH 208 U
* Drug: LIS 18 U


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: INH 69 U (low)<br>single 69 U dose administration of Dance inhaled human insulin using a low-concentration formulation (300 U/mL) | Drug: INH 69 U (low)<br>* inhaled human insulin<br>* Other names: Dance-501;|
| Experimental: INH 69 U (high)<br>single 69 U dose administration of Dance inhaled human insulin using a high-concentration formulation (900 U/mL) | Drug: INH 69 U (high)<br>* inhaled human insulin<br>* Other names: Dance-501;|
| Experimental: INH 139 U<br>single 139 U dose administration of Dance inhaled human insulin using a high-concentration formulation (900 U/mL) This arm was repeated in order to evaluate intra-subject variability. | Drug: INH 139 U<br>* inhaled human insulin<br>* Other names: Dance-501;|
| Experimental: INH 208 U<br>single 208 U dose administration of Dance inhaled human insulin using a high-concentration formulation (900 U/mL) | Drug: INH 208 U<br>* inhaled human insulin<br>* Other names: Dance-501;|
| Active Comparator: LIS 18 U<br>single 18 U dose administration of subcutaneous insulin lispro using a 100 U/mL formulation This arm was repeated in order to evaluate intra-subject variability. | Drug: LIS 18 U<br>* subcutaneous insulin lispro<br>* Other names: subcutaneous insulin lispro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve for insulin from 0-8 hours (AUCins0-8h) | Assessment of the linearity of the dose-response curves | 0 to 8 hours following each dose | 
| Maximum concentration of insulin (CMaxIns) | Assessment of the linearity of the dose-response curves | up to 12 hours following each dose | 
| Area under the curve for glucose infusion rate from 0-12 hours (AUGgir0-12h) | Assessment of the linearity of the dose-response curves | 0 to 8 hours following each dose | 
| Maximum glucose infusion rate (GIRmax) | Assessment of the linearity of the dose-response curves | up to 12 hours following each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability | Relative delivery efficiency (FREL) of inhaled human insulin (INH) compared to subcutaneous injected insulin lispro (LIS) | 0 to 8 hours following each dose |