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

MannKind

Status and phase

Completed

Phase 2

Conditions

Type 2 Diabetes Mellitus

Treatments

Drug: Technosphere Insulin

Drug: Technosphere Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT00511732

MKC-TI-005

Details and patient eligibility

About

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

Enrollment

227 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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).