| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Male or female nonsmoking patients 18 years of age or older; have had type 2 diabetes mellitus for at least 6 months at study entry and have been treated with one or more oral antihyperglycemic medications on a stable dose for at least 6 weeks (3 months for thiazolidinediones [TZDs]) and once-daily insulin glargine for at least 4 months, have FEV1 and DLCO >70% predicted, and have an HbA1c between 7.5% and 9.5% at screening. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10012641 |
| E.1.2 | Term | Diabetic |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is to compare, in patients who at study entry have type 2 diabetes not optimally controlled by one or more oral antihyperglycemic medications plus once-daily insulin glargine, a regimen including mealtime HIIP without insulin glargine (“HIIP only” group) versus a regimen including intensified insulin glargine without mealtime HIIP (“intensified glargine” group), with respect to mean change in HbA1c from baseline to endpoint (6 months). Superiority with respect to HbA1c will be concluded if the upper limit of the 95% confidence interval for the treatment difference (“HIIP only” minus “intensified glargine”) 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%.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To compare the “HIIP only” group versus the “intensified glargine” group, “HIIP + intensified glargine” group versus the “intensified glargine” group, and the “HIIP + intensified glargine” group versus the “HIIP only” group, with respect to the following after 24 weeks and 52 weeks (if applicalbe) of treatment: mean change in HbA1c from baseline to various timepoints, the proportion of patients achieving HbA1c <7%, achieving HbA1c less or equal 6.5%, insulin dose requirements, hypoglycemia, and treatment-emergent adverse events.
• To compare the “intensified glargine” group (no HIIP exposure) versus the “HIIP
exposure” group (“HIIP only” and “HIIP + intensified glargine” groups combined)
with respect to the following after 24 weeks and 52 weeks (if applicable) of treatment: safety as assessed by insulin antibody levels; pulmonary function testing (PFT)
• To assess inhaler reliability in patients randomized to treatment with HIIP. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal 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 described below:
[1] Are male or female who are 18 years of age or older,
[2] Have had type 2 diabetes mellitus for at least 6 months’ duration at study entry,
[3] Have been treated with the following regimen: one or more oral anti-hyperglycemic medications on a stable dose for at least 6 weeks (3 months for thiazolidinediones [TZDs]) AND once-daily insulin glargine for at least 4 months
[4] Have HbA1c ≥7.5 and ≤10.5% at screening
[5] If female, are not breastfeeding
AND
If female and of childbearing potential must
• test negative for pregnancy at the time of screening
• intend not to become pregnant during the study,
• agree to use a reliable method of birth control
[6] Are nonsmokers, have not smoked for at least 6 months prior to entering the study, and agree not to smoke. Serum cotinine
level must be <20 ng/mL at screening.
[7] Are able to perform pulmonary function testing,
[8] Have PFTs graded as “A,” “B,” or “C” in quality
[9] Have a chest x-ray without evidence of clinically significant pulmonary abnormalities
[10] Have signed and dated the informed consent document. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[1] Are investigative site personnel directly affiliated with the study, and/or their immediate families.
[2] Are Lilly or Alkermes employees
[3] 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
[4] Patients who have previously completed or withdrawn from this study or any study investigating any form of inhaled insulin and took one or more doses of inhaled insulin, or have previously taken any form of inhaled insulin
[5] 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.
[6] Have had more than two episodes of severe hypoglycemia during the 6 months prior to study entry
[7] Have had more than one hospitalization or emergency room visit due to poor diabetic control during the 6 months prior to study entry,
[8] Have had a lower respiratory infection in the 3 months prior to screening, evidenced by diagnosed pneumonia
[9] 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),
[10] 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,
[11] 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
[12] Have a history of angina, myocardial infarction, or Functional Capacity Class III/IV cardiac disease within the 6 months prior to study entry,
[13] Have an active or untreated malignancy, or have been in remission from a clinically significant malignancy for less than 5 years
[14] Have a current or past history of lung cancer
[15] Have a history of lung transplantation
[16] 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,
[17] Are taking or have taken exenatide (Byetta™) within 6 weeks,
[18] Require more than 150 U/day of insulin glargine,
[19] Have any other condition (including reported drug abuse, alcohol abuse, or psychiatric disorder) that, in the opinion of the investigator, precludes the patient from following and completing the protocol,
[20] Fail to satisfy the investigator of suitability to participate for any other reason. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy: The primary efficacy measure is the HbA1c change from baseline to 6 months between the “HIIP only” and “intensified glargine” groups. The secondary measures of the study are to compare “HIIP only” versus “intensified glargine,” “HIIP + intensified glargine” versus “intensified glargine” versus “HIIP only” in patients who have been treated for 6 months with respect to the following parameters: mean change in HbA1c from baseline to timepoints (including comparison for change in HbA1c from baseline to endpoint for “HIIP + intensified glargine” versus “intensified glargine” and “HIIP + intensified glargine” versus “HIIP only”), 8-point SBGM profiles (blood glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, blood glucose measurements at bedtime and 3 a.m.); 2-hour blood glucose excursions for the morning, midday, and evening meals; proportion of patients who achieve or maintain an HbA1c ≤6.5% and <7.0%; daily insulin dose requirements (total, preprandial, and basal insulin); standard fasting lipid profile, patient-reported outcomes questionnaires to assess psychological well-being, diabetes-related symptoms, treatment satisfaction, and insulin delivery system satisfaction; and insulin inhaler reliability as assessed by laboratory assessment of inhalers returned for patient complaint.
Safety Measures: Insulin antibody levels (total insulin antibodies only); mean change from baseline in pulmonary function tests (FEV1, FVC, FEV1/FVC, TLC, DLCO); difference from baseline in cough and other pulmonary symptoms using the PSQ; rate per 30 days and incidence of hypoglycemic episodes (total, severe and nocturnal); treatment-emergent adverse events; vital signs (body temperature, systolic blood pressure, diastolic blood pressure, pulse rate, and respiratory rate); and changes from baseline in body weight.
Health Outcomes: Patient-reported general well-being, diabetes-associated symptoms, diabetes treatment satisfaction, and evaluation of insulin delivery systems using the 12-item Well-Being Questionnaire
(W-BQ12); the Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia Subscales of the Diabetes Symptom Checklist-Revised (DSC-R); the Diabetes Treatment Satisfaction Questionnaire Status Version (DTSQs); and the Insulin Delivery System Questionnaire (IDSQ), respectively.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Diabetes oral treatment combinations and Lantus (insulin glargine) |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the trial is the last visit of the last subject undergoing the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 21 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 21 |
Print
