18-Week, Randomized, Double-blind, Placebo Controlled, Forced Titration Study of Patients With Type 2 Diabetes
Phase 2
Completed
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Drug: Technosphere InsulinDrug: Technosphere Placebo
- Registration Number
- NCT00511732
- Lead Sponsor
- Mannkind Corporation
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 227
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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Technosphere Insulin Technosphere Insulin - Technosphere Inhalation Powder Technosphere Placebo -
- Primary Outcome Measures
Name Time Method 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. at weeks 4, 6, 11 and 17 Timepoints: 0 minutes (before meal) and at 15, 30, 60, 90, 120, 180, 240, and 300 minutes after TI administration
Area under the plasma glucose concentration versus time (AUCglucose) compared to week 6 (baseline) at weeks 4, 6, 11 and 17 Timepoints: 0 minutes (before meal) and at 15, 30, 60, 90, 120, 180, 240, and 300 minutes after Technosphere Placebo administration
- Secondary Outcome Measures
Name Time Method 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