Type 2 diabetes mellitus. MedDRA version: 9.1 Level: PT Classification code 10012601 Term: Diabetes mellitus
Conditions
Interventions
Product Name: Technosphere®/Insulin
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Insulin Human rDNA
CAS Number: 11061-68-0
Other descriptive name: Insulin Human, USP
Conc
Sponsors
MannKind Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible subjects must meet all of the following inclusion criteria: 1. Males and females = 18 and = 70 years of age; 2. Clinical diagnosis of type 2 diabetes mellitus for = 12 months; 3. Receiving diabetes treatment with insulin for a minimum of 3 months; 4. Body Mass Index (BMI) of = 34 kg/m2 and = 25 kg/m2; 5. HbA1c = of 8.5% based upon results from a central laboratory; 6. PFTs: • An FEV1 to FVC ratio = 70% and an FVC = 80%; • Amendment 1: FEV1 = 70% predicted; FEV1/FVC ratio = 70% • Single-breath carbon monoxide diffusing capacity (DLco uncorrected) = 70% of Predicted (Miller) 7. Urine cotinine of = 100ng/dL 8. Be willing to sign a written Informed Consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Total daily insulin requirement of = 1.2 U/kg body weight; 2. Use of Symlin® (pramlintide acetate) and/or Byetta® (exenatide) within the preceding 8 weeks; 3. Two or more severe hypoglycemic episodes within 6 months of screening; 4. Any hospitalization or emergency room visit due to poor diabetic control within 6 months of Screening; 5. Severe complications of diabetes 6. Previous exposure to any inhaled insulin product; 7. Currently using an insulin delivery pump; 8. Allergy or known hypersensitivity to insulin or to any of the drugs to be used in the trial or a history of hypersensitivity to Technosphere®/Placebo, T/I or to drugs with a similar chemical structure; 9. Any clinically important pulmonary disease, confirmed by documented history, pulmonary function testing, or radiologic findings; 10. Chronic use of systemic steroids; 11. Inability to perform PFT maneuvers to meet the recommended ATS standards of acceptability and repeatability; 12. Significant improvement in spirometry following bronchodilation defined as at least 12% and a 200 mL increase in either the FVC or the FEV1; 13. Active respiratory infection; however, the subject may return for Screening, Visit 1, after 30 days from resolution of the respiratory condition. 14. Clinically significant major organ system disease such as: - Seizure disorder; - Significant cardiovascular dysfunction and/or history within 3 months of Screening, such as congestive heart failure (NYHA Class III or IV; Appendix B) or serious arrhythmia (Amiodarone is an exclusionary medication), myocardial infarction, cardiac surgery, recurrent syncope, transient ischemic attacks or cerebrovascular accident; - Uncontrolled hypertension with a systolic blood pressure of >160 mm Hg and/or diastolic blood pressure > 95 mm Hg at screening, despite pharmacologic treatment; - Clinical nephrotic syndrome or renal dysfunction or disease, serum creatinine > 2.0 mg/dL in males and > 1.8 mg/dL in females and/or Blood Urea Nitrogen (BUN) > 50 mg/dL; - Cancer (other than an excised cutaneous basal cell carcinoma) within the past 5 years or any history of lung neoplasms; - History of active viral and/or cirrhotic hepatic disease and/or abnormal liver enzymes, as evidenced by serum aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] and/or gamma glutamyl-transferase [GGT] = 3x Upper Limit of Normal (ULN); - Active infection eg, Human Immunodeficiency Virus (HIV), Hepatitis, or history of severe infection within 30 days of Visit 1 (Screening); - Anemia (hemoglobin value below lower limit of normal); - A previous diagnosis of systemic autoimmune or collagen vascular disease requiring prior or current treatment with systemic corticosteroids, cytotoxic drugs or penicillamine; - Any concurrent illness, other than diabetes mellitus and mild COPD, not controlled by a stable therapeutic regime as judged by the investigator; 15. Current or previous chemotherapy or radiation therapy that may result in pulmonary toxicity; 16. Clinically significant abnormalities on screening laboratory evaluation (unless discussed with and approved by the Medical Monitor); 17. Female subjects who are pregnant, lactating or planning to become pregnant during the clinical trial period; 18. Female subjects of childbearing potential (defined as pre-menopausal and not surgically sterilized or post-menopausal for less than 2 years) not practicing adequate birth control. 19. Current drug or alcohol abuse, or a history of drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to assess EGP after dosing with TI Inhalation Powder and compare it to EGP after sc administration of insulin lispro or inhalation of Exubera insulin during a meal challenge with 12 fluid ounces of Boost plus®.;Secondary Objective: The secondary objectives of this trial are to: • Assess EGP after dosing with TI Inhalation Powder in comparison to EGP after sc administration of Insulin Lispro and inhalation of Exubera insulin during a euglycemic glucose clamp procedure. • Characterize the pharmacokinetic and pharmacodynamic properties of TI Inhalation Powder, Insulin Lispro or Exubera insulin. • Assess the effect of TI Inhalation Powder, Insulin Lispro or Exubera insulin on endogenous insulin secretion. • Assess the effect of the 3 treatments on C-peptide, glucagon and free fatty acids (FFA) concentrations.;Primary end point(s): EGP, area over the concentration-time curve (AOC) for EGP (AOCEGP), minimum (EGPmin), and time to (tEGPmin) after a meal challenge with Boost Plus®. | — |
Countries
Germany
Outcome results
None listed