18-Week, Randomized, Double-blind, Placebo Controlled, Forced Titration Study of Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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Designed to evaluate dose response of force-titrated prandial administration of TI as compared to placebo (TP) in subjects with Type 2 diabetes who were suboptimally controlled

Official Title
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A Randomized, Double-blind, Controlled, Stepwise Titration Study to Evaluate Dose Response to Prandial Administration of Inhaled Technosphere/Insulin or Technosphere in Patients With Type 2 Diabetes Mellitus Who Are Sub-optimally Treated

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Technosphere Insulin
* Drug: Technosphere Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and females patients from 18 to <80 years of age Clinical diagnosis of type 2 diabetes mellitus Duration of diabetes of >3 years and <20 years Glycemic control at upper end of acceptable level or sub-optimal in control (HbA1c between 7.0% and 12?0%) Confirmation of diagnosis of diabetes such as a history of 2 hour postprandial blood glucose >11.1 mmol/L (200 mg/dL) or following a glucose tolerance test A minimum of 2 months of treatment with a stable dose of one or more of the following anti-hyperglycemic agents: sulphonylureas, alpha glucosidase inhibitors, metformin, meglitinides, thiazolidinediones and/or Lantus basal insulin therapy FBG:>6 mmol/L (108 mg/dL) C-peptide: >0.5 nmol/L BMI <38 kg/m2 Baseline DLco, FVC, FEV1 >75% of predicted normal Subjects who, in the opinion of the Investigator, will be able to complete this study Written informed consent Exclusion Criteria: Severe complications of diabetes including history of: blindness from or grade III or IV diabetic retinopathy, renal failure requiring dialysis or transplantation, amputation of limbs or digits related to diabetic vasculopathy or foot ulcers Treatment with another investigational drug within 3 months prior to study entry and for the duration of the study History of drug or alcohol dependency Significant hepatic disease (as evidenced by ALT or AST >3 times the normal upper reference range or bilirubin >1.5 times the normal upper reference range) Significant renal disease (as evidenced by creatinine >1.5 mg/dL for males or >1.3 mg/dL for females) or proteinuria >1,000 mg/24 hours History of chronic obstructive pulmonary disease, or history of other known chronic pulmonary diseases, such as reactive airway disease, chronic bronchitis, emphysema, or asthma Heart disease graded as class III or class IV according to New York Heart Association criteria Prior treatment with , or participation in a clinical study involving an inhaled insulin product Smokers Current use of preprandial or prandially administered fast-acting or rapid acting insulin or insulin analogs Previous participation in a TI or TP clinical trial Allergy to insulin or to any drugs to be used as part of the clinical trial History of malignancy within 5 years of study entry (other than basal cell carcinoma) Anemia (hemoglobin level less than 11 g/dL for females or 12 g/dL for males at study entry) Diagnosis of Acquired Immunodeficiency Syndrome (AIDS) and Aids Related Complex A major psychiatric disorder that will preclude satisfactory participation in this study Subjects who have had a myocardial infarction or stroke within the preceding 6 months Prior diagnosis of systemic autoimmune or collagen vascular disease requiring previous or current treatment with systemic corticosteroids, cytotoxic drugs, or penicillamine History of severe or multiple allergies Progressive fatal disease Recent loss (within the past 2 months) of >5% of body weight Evidence of moderate or greater ketones in urine or history of ketoacidosis Use of medications known to modify glucose metabolism or the ability to recover from hypoglycemia such as oral, parenteral and inhaled steroids, or greater than 25 mg hydrochlorothiazide daily Women who are pregnant or lactating Women of childbearing potential practicing inadequate birth control (adequate birth control is defined as using oral contraceptives, condoms or diaphragms with spermicide, intrauterine devices, or surgical sterilization).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Technosphere Insulin<br> | Drug: Technosphere Insulin<br>* Technosphere Insulin Inhalation Powder<br>|
| Placebo Comparator: Technosphere Inhalation Powder<br> | Drug: Technosphere Placebo<br>* Technosphere Inhalation Powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c change from baseline (week 6) to end of treatment (week 17) |  | measured from week 6 (baseline) to week 17 | 
| Area under the plasma glucose concentration versus time (AUCglucose) compared to week 6 (baseline. | Timepoints: 0 minutes (before meal) and at 15, 30, 60, 90, 120, 180, 240, and 300 minutes after TI administration | at weeks 4, 6, 11 and 17 | 
| Area under the plasma glucose concentration versus time (AUCglucose) compared to week 6 (baseline) | Timepoints: 0 minutes (before meal) and at 15, 30, 60, 90, 120, 180, 240, and 300 minutes after Technosphere Placebo administration | at weeks 4, 6, 11 and 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting blood glucose concentration compared to week 6 (baseline) |  | at weeks 4, 6, 11 and 17 | 
| Safety variables included adverse events (AEs), clinical laboratory tests, vital signs and physical examinations |  | 18 weeks |