| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Male or female non smoking adults (18-100 years old), diagnosed type 2 Diabetes Mellitus for at least 6 months duration at study entry. Taking at least one or more oral anti-hyperglycemic medication and are insulin-naïve. They should have HbA1c between 7.5 and 11.0. |
|
| MedDRA Classification |
| 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 objectives are to test the hypothesis that:
For insulin-naïve patients whose type 2 diabetes is not optimally controlled by 2 or more oral antihyperglycemic medications (including patients who are taking only one oral agent but are considered to be appropriate candidates for insulin therapy), patients whose diabetes care options include Human Insulin Inhalation Powder (HIIP) (“standard options + HIIP”), as compared with patients whose options do not include HIIP (“standard options”), will achieve:
• Superior acceptance of insulin therapy, as measured by the proportion of patients
in each group who are using insulin at study endpoint.
• Noninferior glycemic control, as measured by mean change in HbA1c from baseline
to study endpoint, with noninferiority margin of 0.3%.
• Superior glycemic control, as measured by mean change in HbA1c from baseline to
study endpoint. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows:
1) To compare the following in patients who have been in the “standard options” group or “standard options + HIIP” group for different time(s) throughout the 9-month study period:
proportion of patients using insulin at intermediate time points during the study, mean change in HbA1c from baseline to intermediate time points during the study, safety as assessed by adverse events,
patient-reported outcomes measurements to assess general well-being
2) For patients who started any form of insulin, to assess the following:
type(s) of insulin therapy used and insulin dose requirements, insulin antibody levels, and patient evaluation of insulin delivery system.
3) For patients choosing HIIP, to assess the following:
forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and total lung capacity (TLC), and diffusing capacity of the lung for carbon monoxide (DLCO) |
|
| 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:
[1] Male or female patients who are between 18 and 100 years of age.
[2] Patients who have had type 2 diabetes mellitus for at least 6 months’ duration at study entry.
[3] Patients who are taking at least 2 oral antihyperglycemic medications for at least 3 months, are on a stable dose of oral antihyperglycemic medication for at least 6 weeks, and are insulin-naïve. Additionally, patients who are taking only one oral agent but are considered to be appropriate candidates for insulin therapy may be entered into the study.
[4] Patients who have an HbA1c ≥7.5% and ≤11.0% at screening.
[5] Female patients who are not breastfeeding.
• If female patients are of childbearing potential they must:
o test negative for pregnancy at the time of screening based on a blood serum or urine test,
o intend not to become pregnant during the study,
o agree to use a reliable method of birth control 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 <20 ng/mL at screening.
• If the patient is a nonsmoker for a period of ≥6 months, and the serum cotinine level is ≥20 and ≤100 ng/mL, the patient may undergo retesting of serum cotinine once within 4 weeks, prior to randomization.
[7] Patients who are able to perform pulmonary function testing, according to guidelines from the American Thoracic Society (ATS 1995).
[8] Patients who have signed and dated the screening informed consent document. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[1] Patients who are investigative site personnel directly affiliated with the study, or are immediate family of investigative site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[2] Patients who are employed by Lilly or Alkermes, Inc. (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly employees may participate in Lilly-sponsored clinical trials, but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[3] 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.
[4] Patients who are taking or have taken exenatide (Byetta™) within 6 weeks.
[5] Patients who have previously received any form of inhaled insulin, or have completed or discontinued from this study.
[6] Patients who are taking a thiazolidinedione (TZD) dose greater than what is indicated in combination with insulin according to the TZD label in the respective country (e.g., in the United States, rosiglitazone greater than 4 mg daily or pioglitazone greater than 45 mg daily is not currently within product labeling indications). In countries where the combination of the TZD and insulin is not approved, patients taking any TZD at study entry will be excluded.
[7] Patients who have had a lower respiratory infection in the 3 months prior to screening, evidenced by diagnosed pneumonia (on clinical or radiologic grounds).
[8] 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).
[9] Patients who have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) greater than 3 times the upper limit of the reference range.
[10] 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 of the geography.
[11] Patients who have a history of angina, myocardial infarction, or Functional Capacity Class III/IV cardiac disease (as defined by the New York Heart Association [Protocol Attachment IDAW.5]) within the 6 months prior to study entry.
[12] Patients who have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
[13] Patients who have a current or past history of lung cancer.
[14] Patients who have a history of lung transplantation.
[15] 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.
[16] Patients who 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.
[17] Patients who fail to satisfy the investigator of suitability to participate for any other reason.
[18] Patients who have previously completed or withdrawn from this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Acceptance of insulin therapy will be measured by the proportion of patients in each
group who are using insulin at study endpoint.
Glycemic control will be assessed by measuring change in HbA1c from baseline to study endpoint. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Diabetes treatment combinations available, excluding any formulation of inhalative insulin |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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