Male or non pregnant female nonsmoking patients, 18 years of age or older: have had type 2 diabetes mellitus for at least 6 months, and have been treated with one or more oral antihyperglycemic medications for at least 6 weeks (12 weeks for thiazolidinediones [TZDs]), and are insulin-naïve as defined in the protocol, have HbA1c >7.0% and =10.5%, and FEV1 and DLCO >70% of predicted value MedDRA version: 8.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Sponsors
Eli Lilly and Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria at screening or otherwise, as indicated below: [1] male or female patients who are 18 years of age or older, [2] patients who have had type 2 diabetes mellitus, based on the disease diagnosis criteria (Section 4.1.1), for at least 6 months’ duration at study entry, [3] patients who have been treated with the following regimen: • one or more oral antihyperglycemic medications on a stable dose for at least 6 weeks (12 weeks for thiazolidinediones [TZDs]), AND • have been on insulin for 14 days or less throughout life and have not taken insulin within 6 months, AND • are candidates for insulin therapy, in the opinion of the investigator. [4] patients who have HbA1c >7.0% and =10.5% at screening: [5] female patients who are not breastfeeding and if female patients are of childbearing potential they must • test negative for pregnancy at the time of screening • intend not to become pregnant during the study, and • agree to use a reliable method of birth control during the study. [6] patients who are nonsmokers, have not smoked for >6 months prior to entering the study, and agree not to smoke (cigars, cigarettes, or pipes) or use smokeless tobacco for the duration of the study. [7] patients who are able to perform pulmonary function testing, according to guidelines from the American Thoracic Society (ATS) (1995), [8] patients who have PFTs graded as “A,” “B,” or “C” in quality and satisfy all of the following criteria for pulmonary function tests (PFT): • DLCO >70% of predicted • FEV1/FVC > lower limit of normal and FEV1 >70% predicted • Patients should be able to perform at least three acceptable FEV1, FVC, and DLCO maneuvers [9] patients who have a chest x-ray (posteroanterior and lateral views) without evidence of clinically significant pulmonary abnormalities, in the opinion of the investigator [10]patients who have signed and dated the informed consent document. 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: Patients will be excluded from the study if they meet any of the following criteria: [11] are investigative site personnel directly affiliated with the study, and/or their immediate families. [12] patients are Lilly employees or are employed by Alkermes. Immediate family of Lilly or Alkermes employees may participate in Lilly-sponsored clinical trials, but are not permitted to participate at a Lilly facility. [13] patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry, [14] patients who have previously received any form of inhaled insulin, or have completed or discontinued from this study, [15] patients who are taking a TZD dose greater than what is indicated in combination with insulin according to the TZD label in the respective country. In countries where the combination of the TZD and insulin is not approved, patients taking any TZD at study entry will be excluded. [16] patients who have had more than two episodes of severe hypoglycemia during the 6 months prior to study entry [17] patients who have had more than one hospitalization or emergency room visit due to poor diabetic control during the 6 months prior to study entry, [18] patients who have had pneumonia in the 3 months prior to screening, on clinical or radiologic grounds, [19] patients who have received systemic glucocorticoid therapy within the 3 months prior to study entry (topical preparations, nasal preparations, intra-articular administration, as well as physiologic replacement for Addison’s Disease and hypopituitarism are permitted), [20] patients who have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransaminase/serum glutamic pyruvic transaminase (ALT/SGPT) greater than three times the upper limit of the reference range, [21] patients who have a history of renal transplantation, are currently receiving renal dialysis, or have a serum creatinine >2.0 mg/dL (177 µmol/L) if not on metformin; or if on metformin at study entry, have a serum creatinine above what is contraindicated in the metformin label in the respective country (for example, in the United States, =1.5 mg/dL [132 µmol/L] for males or =1.4 mg/dL [123 µmol/L] for females), [22] patients who have a history of angina, myocardial infarction (MI), or Functional Capacity Class III/IV cardiac disease (as defined by the New York Heart Association within the 6 months prior to study entry, [23] patients who have an active or untreated malignancy, or have been in remission from a clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) for less than 5 years, [24] patients who have a current or past history of lung cancer, [25] patients who have a history of lung transplantation, [26] patients who have a current or past history of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, alpha-1 antitrypsin deficiency, or other clinically relevant pulmonary disease that, in the opinion of the investigator, would preclude participation in the study due to safety concerns, or confound data interpretation, [27] patients who are taking or have taken exenatide (Byetta™) or other incretin mimetics that are not approved for use with insulin during the prior 8 weeks, [28] patients who have any other condition (including reported drug abuse, alcoho
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study, in suboptimally-controlled insulin-naïve individuals with type 2 diabetes, is to demonstrate that a simple approach for adding HIIP to oral antihyperglycemic medication can achieve, within 6 months, glycemic control similar to a more aggressive approach. The two treatment regimens algorithms (Algorithm A versus Algorithm B) will be compared with respect to mean change in HbA1c from baseline to endpoint (6 months). Noninferiority with respect to HbA1c will be concluded if the upper limit of the 95% confidence interval for the treatment difference (Algorithm A – Algorithm B) is less than 0.4%. ;Secondary Objective: The secondary objectives of the study are: 1) To compare the two dose titration algorithm groups with respect to the following: • mean change in HbA1c from baseline to 2 months, and 3 months • daily insulin dose requirements • time to maximum dose; time to 90% maximum dose; and time to achievement of 75% of SBGM targets • the proportion of patients achieving HbA1c <7% and, in a separate analysis, achieving HbA1c =6.5% • 8-point SBGM profile, 4-point SBGM profile, and total number of blood glucose measurements per week • hypoglycemia • patient-reported energy; fatigue and cognitive distress symptoms; diabetes treatment satisfaction; and evaluation of the insulin delivery system • treatment-emergent adverse events • safety as assessed by insulin antibody levels; pulmonary function testing (PFT) and diffusing capacity of the lung for carbon monoxide (DLCO); Pulmonary Symptoms Questionnaire (PSQ); body weight. 2) To assess inhaler reliability. ;Primary end point(s): Efficacy: The primary efficacy outcome is the mean change in HbA1c from baseline to endpoint. An analysis of covariance (ANCOVA) model will be used to establish the noninferiority of Algorithm A to Algorithm B. In addition to the primary efficacy analysis of HbA1c for noninferiority, the following outcomes will be analyzed for efficacy with a | — |
Countries
Austria, Belgium, Spain
Outcome results
None listed