E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
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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.
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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 on glycaemic control To assess … • the percentage of subjects achieving HbA1c ≤7.5%, ≤7.0%, and ≤6.5% • the proportion of subjects achieving HbA1c ≤7.0% without symptomatic hypoglycemia • the plasma glucose intra-subject variability • the safety and tolerability To evaluate… • 8-point plasma glucose profiles • the lipid profile • body weight changes • basal/bolus insulin doses • biomarkers To assess and compare… • the effect on fasting plasma glucose • the incidence of hypoglycaemic episodes in the treatment groups • Pulmonary Function Test • Patient Reported Outcomes To investigate… • reversibility of changes in insulin antibodies • reversibility of changes in pulmonary function
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• 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). • Diagnosis of type 2 diabetes according to clinical judgement • Current treatment with any regimen of insulin for ≥ 3 months (with or without a maximum of one OAD) • Males and females, age ≥ 18 years • Body mass index of (BMI) ≤ 40.0 kg/m2 • HbA1c ≤ 11.0 % (analysis from central laboratory) • Able and willing to perform self-monitoring of plasma glucose according to the protocol and to keep a diary •Able and willing to be treated with a basal regimen (once or twice daily) and bolus regimen (3 times per day) • FEV1 ≥ 70 % of predicted value |
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E.4 | Principal exclusion criteria |
• 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]) • Total daily insulin dosage > 100 Units • 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 • Chest X-ray with any clinically significant abnormalities evaluated by a radiologist • Unresolved symptoms and signs of an upper respiratory tract infection (URI) within 3 weeks prior to screening • Current acute or chronic pulmonary disease (excluding asthma) including chronic obstructive pulmonary disease, bronchiectasis, chronic bronchitis, sarcoidosis, and pulmonary fibrosis • History of hypoglycaemic unawareness and/or two or more severe hypoglycaemic episodes in the past year as judged by the Investigator • Treatment with systemic steroids within the past 2 months prior to screening • 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) • 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 ≥ 180 mmHg or sitting diastolic blood pressure ≥ 100) or history of proliferative retinopathy or maculopathy requiring treatment • Renal insufficiency (creatinine ≥ 2 mg/dL; ≥ 180 µmol/L) • 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
HbA1c change from baseline after 52 weeks |
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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) | 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 | 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
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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 | 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 |