Type II diabetes MedDRA version: 14.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Insulina Humana en Polvo para Inhalación
Product Code: LY041001
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Insulana Humana
Current Sponsor code: LY041001
Sponsors
Lilly S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] male or female patients who are 18 years of age or older, [2] patients who have had type 2 diabetes mellitus for at least 6 months? duration at study entry, [3] patients who have been treated with one or more OAMs on a stable dose for at least 6 weeks (12 weeks for thiazolidinediones [TZDs]), AND ? have been on insulin for 30 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 ?8.0 and ?10.5% at screening, ? If the HbA1c criterion is not met at the first screening visit, the patient may undergo retest of HbA1c once within a 3-month period. If less than 1 month has passed since the initial screening, only the HbA1c test will be repeated. If more than 1 month, but less than 3 months have passed, the entire screening panel will be repeated except cotinine. ? Retesting may occur as long as the screening period for the study is still ongoing at the time of the retest. [5] if female, patients must not be breastfeeding, and if female patients are of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopausal), they must ? test negative for pregnancy at the time of screening based on a urine or serum test, ? intend not to become pregnant during the study, and ? agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant®; a reliable barrier method of birth control [diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices]; partner with vasectomy) during the study. [6] patients who are nonsmokers, have not smoked for at least 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. Serum cotinine level must be 70% of predicted, ? FEV1/FVC > lower limit of normal and FEV1 >70% predicted, ? patients should be able to perform at least 3 acceptable FEV1 and FVC maneuvers, and 2 acceptable DLCO maneuvers. For each test, 2 of the maneuvers must be reproducible (within 0.20 L for FEV1 and FVC; and within 2.5 standard DLCO units for DLCO). ? If the patients are not able to meet the reproducibility criteria for FEV1, FVC, or DLCO maneuvers, they may return for retest within a 4-week period. ? If the grade for FEV1, FVC, or DLCO is ?D? or ?F,? patients may return for retest within a 4-week period. ? Retesting may occur as long as the screening period is still ongoing at the time of the retest. [9] patients who have a chest x-ray (posteroanterior and lateral views) without evidence of clinically significant pulmonary abnormalities (including severe bullous disease), in the opinion of the investigator. (Scarring due to inactive tuberculosis is not exclusionary. If an x-ray (posteroanterior and lateral view
Exclusion criteria
Exclusion criteria: [11] are investigative site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted, [12] are Lilly or Alkermes employees, [13] 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 1 or more doses of any form of inhaled insulin, or have previously 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 (for example, in the United States, rosiglitazone greater than 4 mg daily or pioglitazone greater than 45 mg daily is not currently indicated). 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 2 episodes of severe hypoglycemia during the 6 months prior to study entry (see Section 5.9 for information about severe hypoglycemia), [17] patients who have had more than 1 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 3 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 ?mol/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 ?mol/L] for males or ?1.4 mg/dL [123 ?mol/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 [Protocol Attachment IDAZ.5]) 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 diagnosis 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 during the prior 6 weeks exenatide (Byetta?) or other incretin mimetics that are not approved for use with i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this randomized, crossover study is to compare, in approximately 132 insulin-naïve patients with type 2 diabetes who have inadequate glycemic control on one or more oral antihyperglycemic medications (OAM), a regimen adding mealtime HIIP (?HIIP+orals?) versus a regimen adding insulin glargine (?glargine+orals?) with respect to change in HbA1c from baseline (Visit 3) to endpoint. Superiority with respect to HbA1c will be concluded if the upper limit of the 95% confidence interval for the treatment difference (?HIIP+orals? inus ?glargine+orals?) is less than zero. Noninferiority will be concluded if this upper limit is less than 0.4%, but greater than or equal to 0.0%.;Secondary Objective: 1) To compare the ?HIIP+orals? treatment versus ?glargine+orals? treatment, with respect to the following: ? Mean change in HbA1c from baseline, ? % of patients who achieve or maintain HbA1c <7% and, in a separate analysis, ?6.5%, ? 8-point self-monitored blood glucose profiles obtained at baseline and at the end of each study period, ? Total insulin dose requirements, ? Patient-reported preference, evaluation of insulin delivery system satisfaction, lifestyle impact of insulin delivery system, diabetes treatment satisfaction, energy, fatigue, cognitive distress symptoms, hyperglycemia symptoms, ease of dosing, positive well-being, negative well-being, and hypoglycemia symptoms, ? Hypoglycemia ? Changes in body weight, ? Adverse events, ? Safety as assessed by total pulmonary function testing; diffusing capacity of the lung for carbon monoxide; and Pulmonary Symptoms Questionnaire, ? Standard fasting lipid profile. 2) To assess inhaler reliability.;Primary end point(s): The primary efficacy measure is change in HbA1c from baseline (measured at Visit 3) to the endpoint of each crossover period.;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary measures of the study are to compare ?HIIP+orals? versus ?glargine+orals? with respect to the following parameters: ? change in HbA1c from baseline to 12 and 24 weeks, ? the proportion of patients who achieve or maintain an HbA1c <7% and, in a separate analysis, ?6.5% at 12 weeks and endpoint, ? 8-point SMBG profiles at endpoint, o preprandial blood glucose measures before morning, midday, and evening meals, and overall preprandial blood glucose o postprandial blood glucose measures 2 hours after morning, midday, and evening meals, and overall postprandial blood glucose o bedtime blood glucose measure, o 3 a.m. blood glucose measure. o daily average blood glucose measure. o 2-hour blood glucose excursions at endpoint (the difference between the preprandial and the 2-hour postprandial blood glucose values) for the morning, midday, evening meals, and overall 2-hour excursions (based on 8-point SMBG data). o M-value (measure of intra-day blood glucose variability). o MODD (measure of inter-day blood glucose variability). ? Total insulin dose requirements, ? fasting lipid profile at endpoint (high-density lipoprotein cholesterol [HDL-C], total cholesterol, triglycerides, and low-density lipoprotein cholesterol [LDL-C]), Human Insulin Inhalation Powder (HIIP) ? Inhaler reliability in patients using HIIP defined by number of inhalers returned for patient complaint divided by the number of inhalers dispensed.;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Countries
Brazil, Indonesia, Spain, United States
Contacts
Public ContactClinical Operations
Lilly S.A.
Outcome results
None listed