E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
|
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 |
To compare the effect of pre-prandial inhaled human insulin administered with AERx to subcutaneous injections of pre-prandial insulin aspart both in combination with insulin detemir on glycaemic control as measured by change in HbA1c from baseline in subjects with type 2 diabetes after 52 weeks treatment |
|
E.2.2 | Secondary objectives of the trial |
To compare the effect of pre-prandial inhaled human insulin administered with AERx to subcutaneous injections of pre-prandial insulin aspart both in combination with insulin detemir on glycaemic control as measured by change in HbA1c in subjects with type 2 diabetes after 104 and 116 weeks treatment To assess and compare the effect on fasting plasma glucose To evaluate 8-point plasma glucose profiles To assess the percentage of subjects achieving HbA1c 8804;7.5 , 8804;7.0 , and 8804;6.5 after 52 and 104 weeks To assess the proportion of subjects achieving HbA1c 8804;7.0 without symptomatic hypoglycaemia confirmed by a plasma glucose value of 4.0 mmol/L 72 mg/dL or any single plasma glucose value of 3.1 mmol/L 56mg/dL in the last 12 weeks of treatment before the visit at 52, 104 and 116 weeks To assess the plasma glucose intra-subject variability performed before breakfast, lunch and dinner during five days in the last week before the visit at |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
6.2 Inclusion Criteria 1. Informed consent obtained before any trial-related activities Trial-related activities are any procedure that would not have been performed during normal management of the subject . 2. Diagnosis of type 2 diabetes according to clinical judgement 3. Current treatment with any regimen of insulin for 8805; 3 months with or without a maximum of one OAD 4. Able and willing to be treated with a basal regimen once or twice daily and bolus regimen 3 times per day 5. Males and females, age 8805; 18 years 6. Body mass index of BMI 8804; 40.0 kg/m2 7. HbA1c 8804; 11.0 analysis from central laboratory 8. Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary |
|
E.4 | Principal exclusion criteria |
1. Previous participation in this trial. Participation is defined as randomisation 2. Pregnant or positive pregnancy test at screening, nursing mother, or unwillingness to use adequate contraception appropriate methods include abstinence and the following methods diaphragm, condom, by partner , intrauterine device, sponge, spermacide or oral contraceptives 3. Total daily insulin dosage 100 Units 4. Current smoking or smoking within the last 6 months regular smoking defined as one cigarette or an equivalent amount of smoking tobacco per day or a positive urine cotinine test on screening laboratory test. Subjects using non-inhalable tobacco products can be included despite a positive urine cotinine test 5. Chest X-ray with any clinically significant abnormalities evaluated by a radiologist 6. Unresolved symptoms and signs of an upper respiratory tract infection URI within 3 weeks prior to screening 7. Current acute or chronic pulmonary disease excluding asthma including chronic obstructive pulmonary disease, bronchiectasis, chronic bronchitis, sarcoidosis, and pulmonary fibrosis 8. Positive screening for Hepatitis B antigen or Hepatitis C antibody 9. Positive screening for Human Immune deficiency Virus HIV 10. History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator 11. Treatment with systemic steroids within the past 2 months prior to screening 12. Impaired hepatic function defined as screening aspartate aminotransferase AST or alanine aminotransferase ALT 8805; 2.5 times upper normal range one re-test analysed at the central laboratory within one week is permitted with the last sample being conclusive 13. Known or suspected allergy to any trial products or related products 14. Clinically significant, active or over the past 12 months disease of the cardiovascular, gastrointestinal, neurological, genitourinary, haematological systems, or has severe uncontrolled treated or untreated hypertension systolic blood pressure 8805; 180 mmHg or sitting diastolic blood pressure 8805; 100 or history of proliferative retinopathy or maculopathy requiring treatment 15. Renal insufficiency creatinine 8805; 2 mg/dL; 8805; 180 mol/L 16. Any conditions that the Investigator judges would interfere with trial participation or evaluation of results 17. Current addiction to alcohol or substances of abuse as judged by the Investigator 18. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation in the trial 19. Participated in another clinical trial and received an investigational drug within the last 4 weeks or received previous treatment with pulmonary insulin other than subjects treated with AERx for more than a total of seven days |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint HbA1c change from baseline after 52 weeks |
|
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |