| 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 | 10045242 |
| E.1.2 | Term | Type II 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® iDMS to rosiglitazone, both in combination with metformin, on glycaemic control (as measured by change in HbA1c from baseline) in subjects with type 2 diabetes, after 26 weeks of treatment. |
|
| E.2.2 | Secondary objectives of the trial |
•To assess and compare the effect on fasting plasma glucose (FPG)
•To evaluate 8-point plasma glucose profiles
•To assess the percentage of subjects achieving HbA1c ≤ 7.5%, ≤ 7.0%, and ≤ 6.5% after 26 weeks
•To evaluate the lipid profile
•To evaluate body weight changes
•To assess the incidence of hypoglycaemic episodes
•To assess and compare pulmonary function tests (PFT)
•To assess and compare patient reported outcomes (PRO)
•To assess and compare health economics parameters
•To assess the safety and tolerability
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 one or two OAD(s) (insulin secretagogues, insulin sensitizers, metformin, glitazones, alpha-glucosidase inhibitors) for ≥ 2 months. Subjects on monotherapy should be at least on half maximum dose for ≥ 2 months
4. 7.5% ≤ HbA1c ≤ 11.0% in subjects on OAD monotherapy, and 7.0% ≤ HbA1c ≤ 10.0% in subjects on OAD combination therapy (analysis from central laboratory)
5. FEV1 ≥ 70 % of predicted value
6.Males and females, age ≥ 18 years
7.Body mass index of (BMI) ≤ 40.0 kg/m2
8.Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary
9. Able and willing to be treated with metformin (up to three times daily) in combination with pre-prandial inhaled insulin using the AERx or tablet treatment
|
|
| E.4 | Principal exclusion criteria |
1.Previous participation in this trial. Participation is defined as randomisation
2.Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice [for Germany, adequate contraception is: implants, injectables, combined oral contraceptives, hormonal IUD, sexual abstinence or vasectomised partner. For United Kingdom, adequate contraceptive measures are sterilisation, intra-uterine device, oral contraceptives or consistent use of barrier methods])
3.Known or suspected allergy to trial products or related products
4.Current regular smoking or regular 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 laboratory test, except if resulting from non-inhalable tobacco products
5.Chest X-ray with any clinically significant abnormalities evaluated by a radiologist
6.Unresolved symptoms and signs of an upper respiratory tract infection (URTI) 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.History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator
9.Cardiac disease defined as: decompensated heart failure (NYHA class I to IV), unstable angina pectoris within the past 6 months of study enrolment, myocardial infarction within the past 12 months and a clinically significant history of arrhythmias or conduction delays on ECG over the past 12 months
10.Clinically significant, active (or over the past 12 months) disease of the gastrointestinal, neurological, genitourinary, haematological systems
11.Severe uncontrolled treated or untreated hypertension (systolic blood pressure ≥ 180 mmHg or sitting diastolic blood pressure ≥ 100 mmHg)
12.Impaired hepatic function defined as screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 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.Renal insufficiency defined as serum creatinine ≥ 1.4 mg/dL (≥ 126 µmol/L) for males and ≥ 1.3 mg/dL (≥ 111 µmol/L) for females, (one retest within a week is permitted)
14.History of proliferative retinopathy or maculopathy requiring treatment
15.Acute or chronic acidosis or if there are plans to have a radiographic material containing iodine
16.Positive screening for Hepatitis B antigen or Hepatitis C antibody
17.Treatment with systemic steroids within the past 2 months prior to screening
18.Current addiction to alcohol or substances of abuse as judged by the Investigator
19.Any conditions that the Investigator judges would interfere with trial participation or evaluation of results
20.Mental incapacity, unwillingness or language barrier precluding adequate understanding or
cooperation in the trial
21.Participated in another clinical trial and received an investigational drug within the last 4 weeks
22.Previous treatment with inhaled insulin, other than treatment with AERx, for more than a total of seven days
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| HbA1c change from baseline after 26 weeks of treatment |
|
| 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 | Information not present in EudraCT |
| 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 57 |
| 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 | No |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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