Dose Response of Dance 501 in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This will be a randomized, open-label, active-controlled, 6-period crossover study. Target population will be subjects with Type 2 Diabetes Mellitus (T2DM)

Detailed Description
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To assess the dose-response and dose-exposure of Dance 501 (Human Insulin Inhalation Solution) administered with the Dance 501 Inhaler.

Official Title
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A Randomized, Open-Label, 6-Period Cross-Over Study to Investigate the Dose Response of Dance 501 (Human Insulin Inhalation Solution and Inhaler) in Subjects With Type 2 Diabetes Mellitus (T2DM)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Inhaled Human Insulin
* Drug: Insulin Lispro (Humalog U-100)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with T2DM. BMI between 25.0 and 40.0 kg/m2. Treated with metformin and/or at least 1 daily injection of insulin for at least 6 months. Non-smoker for at least 5 years. Forced vital capacity and forced expiratory volume in one second is at least 75% normal. Exclusion Criteria: Any condition affecting pulmonary drug absorption. History or presence of cancer except basal cell skin cancer or squamous cell skin cancer. Serious systemic infectious disease during four weeks prior to dosing. Clinically significant abnormal lab values. Proliferative retinopathy and/or severe neuropathy. Recurrent severe hypoglycemia. Current treatment with oral anti-diabetic drugs except metformin, glucagon-like peptide receptor agonists. Current treatment with MAO inhibitors. Unstable Thyroid hormones for at least 3 months. Insufficient glycemic control with significant fluctuations of blood glucose.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, Open-Label, Cross-Over design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dance 501<br>Dance 501(Human Insulin Inhalation Solution and Inhaler) will be administered using the Dance 501 Inhaler. | Drug: Inhaled Human Insulin<br>* Dance 501 administered using the Dance 501 Inhaler<br>* Other names: Dance 501;|
| Active Comparator: Insulin Lispro<br>Insulin Lispro (Humalog®) will be administered by subcutaneous injection. | Drug: Insulin Lispro (Humalog U-100)<br>* Lispro<br>* Other names: Insulin Lispro (Humalog U-100) will be administered by subcutaneous injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Pharmacokinetic Endpoint - PK 1 | Area under the human insulin and insulin lispro concentrations time curves | 0 - 10 hours | 
| Primary Pharmacokinetic Endpoint - PK 2 | Maximum observed concentration of human insulin and insulin lispro | 0 - 10 hours | 
| Primary Pharmacodynamic Endpoint - PD 1 | Area under the glucose infusion rate time curve | 0 - 10 hours | 
| Primary Pharmacodynamic Endpoint - PD 2 | Maximum observed glucose infusion rate | 0 - 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Pharmacokinetic Endpoint - PK 1 | Area under the insulin time curves at different intervals | 0 - 1 hour, 0 - 2 hours, 0 - 8 hours | 
| Secondary Pharmacokinetic Endpoint - PK 2 | Time to maximum insulin concentrations | 0 - 10 hours | 
| Secondary Pharmacokinetic Endpoint - PK 3 | Relative Efficiency of dose corrected ratio of AUC ins for INH and s.c. lispro | 0 - 10 hours | 
| Secondary Pharmacokinetic Endpoint - PK 4 | Onset of appearance (time from trial product administration until the serum insulin concentrations are > LLOQ. | 0 - 10 hours | 
| Secondary Pharmacokinetic Endpoint - PK 5 | Mean residence time of insulin | 0 - 10 hours | 
| Secondary Pharmacodynamic Endpoint - PD 1 | AUC for GIR at different time intervals | 0 - 1 hour, 0 - 2 hours, 0 - 8 hours | 
| Secondary Pharmacodynamic Endpoint - PD2 | Time to maximum glucose infusion rate | 0 - 10 hours | 
| Secondary Pharmacodynamic Endpoint - PD3 | Relative biopotency of dose corrected ratio of AUC GIR for INH and s.c. lispro | 0 - 10 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhaled Insulin