E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 1 diabetes mellitus and many patients with type 2 diabetes mellitus require daily use of insulin for the maintenance of normal glucose homeostasis. At present, insulin can be delivered only by injection. The availability of noninjectable routes of insulin administration may eliminate a barrier to effective therapy and improve the quality of life for many patients with diabetes. |
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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 objective of this study is to test the hypothesis that preprandial HIIP is noninferior to preprandial injectable insulin (regular human insulin or insulin lispro) with respect to mean change from baseline to endpoint in HbA1c in patients with type 1 diabetes treated for approximately 24 months. A noninferiority margin of 0.4% for HbA1c will be used. |
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E.2.2 | Secondary objectives of the trial |
1) To compare preprandial HIIP with preprandial injectable insulin in patients with type 1 diabetes with respect to: - FEV1, FVC and total lung capacity - DLCO - Safety assessed by insulin antibody titers, AEs, episodes of hypoglycemia - Safety using qualitative visual reading of serial HRCT scans of chest - Safety assessed by Six-Minute Walk Test with Borg CR10 scale to assess perceived exertion - Glycemic control assessed by the 8-point self blood glucose monitoring profiles - Proportion of patients who achieve or maintain an HbA1c <7.0% - Insulin dose requirements - Patient-reported outcomes questionnaires to assess psychological well being, health status, and insulin delivery system satisfaction - Resource utilization 2) To assess inhaler reliability in patients randomized to treatment with HIIP 3) To explore differences in cough and other pulmonary symptoms in patients treated with HIIP or preprandial injectable insulin using the PSQ
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Male and female patients who are 18 years of age or older. - Patients who have type 1 diabetes for at least 24 months’ duration at study entry and meet the disease diagnostic criteria as defined by the World Health Organization (WHO) and as confirmed by a C-peptide value <0.5 ng/mL (165 pmol/L) at screening (Visit 1). - Patients who have an HbA1c ≤11% 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. - Patients who are on an insulin regimen involving 2 or 3 preprandial injections per day for at least 2 months. (Patients who are on a regimen that includes pre-mix insulin are appropriate candidates. Patients on insulin pump therapy within the previous 2 months are not appropriate candidates.) - Patients who are a nonsmoker for at least 1 year prior to the study and intend to continue nonsmoking 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 >1 year, and the serum cotinine level is >20 and <100 ng/mL, the patient may undergo retesting of serum cotinine once within a 2-week period. - Female patients who are not breastfeeding, and If female patients are of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal), they: test negative for pregnancy at the time of screening based on a blood serum test intend not to become pregnant during the study 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. - Patients who have signed and dated the informed consent document. - Patients who have PFTs graded as “A,” “B,” or “C” in quality and satisfy all of the following criteria for locally read PFTs: DLCO >70% of predicted. FEV1/FVC > lower limit of normal and FEV1 >70% predicted. Patients should be able to perform at least 3 acceptable FVC and DLCO maneuvers, 2 of which are reproducible - Patients who have a chest x-ray with no evidence of clinically significant pulmonary abnormalities in the opinion of the investigator. (Scarring due to inactive tuberculosis is not exclusionary.) - Patients who are able to perform pulmonary function testing, according to guidelines from the American Thoracic Society (ATS 1995). - Patients who are able to perform the 6MWT. |
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E.4 | Principal exclusion criteria |
- Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. - Are employed by Lilly or Alkermes (that is, employees, temporary contract workers, or designees responsible for conducting the study). Immediate family of Lilly employees may participate in Lilly-sponsored clinical trials, but are not permitted to participate at a Lilly facility. - 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. - Patients who have previously completed or withdrawn from this study or any study investigating any form of inhaled insulin. - Patients who require a daily total insulin dosage greater than 150 U at screening. - Patients who have a current or past history of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, 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. - Patients diagnosed with pneumonia (on clinical or radiological grounds) in the 3 months prior to screening. - 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. - Patients with a history of renal transplantation, are currently receiving renal dialysis, or have a serum creatinine >2.0 mg/dL (177 μmol/L). - Patients who have a body mass index (BMI) >35 kg/m2. - Patients with a history of angina, myocardial infarction (MI), or Functional Capacity Class III/IV cardiac disease within the 6 months prior to study entry. - Patients who have had more than 2 episodes of severe hypoglycemia during the 6 months prior to study entry. - Patients who have had more than 1 episode of diabetic ketoacidosis during the 6 months prior to study entry. - Patients with a history of lung cancer. - Patients with active malignancy, other than basal cell or squamous cell skin cancer. - 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). - Patients who have any other condition (including known drug abuse, alcohol abuse, or psychiatric disorder) that, in the opinion of the investigator, precludes the patient from following and completing the protocol. - Patients who fail to satisfy the investigator of suitability to participate for any other reason.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcomes of this study will be the efficacy measure HbA1c change from baseline to endpoint and the assessment of HIIP effects on important safety parameters. |
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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 | No |
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 | 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) | Yes |
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 | No |
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 |
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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
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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 | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |