E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 1 diabetes Type 2 diabetes Asthma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 |
The primary objective of this trial is to evaluate long-term pulmonary safety profiles comparing preprandial inhaled human insulin with preprandial subcutaneous (sc) injections of insulin aspart, both in combination with basal insulin and/or oral antidiabetic drugs (OADs), in subjects with diabetes and asthma. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare the two treatment groups with respect to: •Long-term safety profiles as measured by electrocardiogram (ECG), funduscopy/fundusphotography, vital signs, physical examination, body weight, laboratory assessments and adverse events (AEs) •Incidence of hypoglycaemic episodes •Glycaemic control as measured by HbA1c and fasting plasma glucose analysed by central laboratory (FPGLab) •Bolus insulin doses •PROs: asthma control questionnaire (ACQ), insulin treatment satisfaction questionnaire (ITSQ) and environmental tobacco smoke questionnaire (ETS-Q)
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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.Able and willing to perform self-measurement of plasma glucose (SMPG) according to the protocol and to keep a diary 3.Diagnosis of type 1 or type 2 diabetes, ie: •type 1 diabetes with an HbA1c ≤ 11.0 % and treated continuously with basal/bolus insulin for at least six months •or type 2 diabetes with an HbA1c ≤ 11.0 % and treated continuously with basal/bolus insulin for at least three months •or type 2 diabetes with an HbA1c ≥7.5 % and ≤ 11.0 % and treated continuously with basal insulin (with or without an OAD except rosiglitazone in EU and in countries that follow EU labeling) for at least two months •or type 2 diabetes with an HbA1c ≥7.5 % and ≤ 11.0 % and treated with one or more OAD(s) (except rosiglitazone in EU and in countries that follow EU labeling) for at least two months 4.Men and women, age ≥ 18 years 5.BMI ≤ 40.0 kg/m2 6. Clinical diagnosis of mild intermittent, mild persistent or moderate persistent asthma according to the NAEPP guidelines for at least six months prior to screening 7. Stable asthma defined as being on stable prescribed maintenance dose of inhaled glucocorticosteroids* during the last four weeks before Visit 1 and not having had an asthma exacerbation requiring an urgent medical visit initiated by the subject or physician and/or treatment with oral or iv glucocorticosteroids within the last six months before Visit 1 * Subjects with mild intermittent asthma should not be treated with inhaled glucocorticosteroids for the last four weeks before Visit 1 8. Airway reversibility with inhaled short-acting β2-agonist according to ATS/ERS guidelines showing an increase in FEV_1 ≥12% and 200 mL compared to baseline or a positive methacholine or histamine bronchoprovocation test according to local guidelines with PC_20 ≤ 8 mg/mL or PD_20 ≤ 7.8 µmol or a documented airway reversibility test with inhaled short-acting β2-agonist showing an increase in FEV_1 ≥ 12% and 200 mL compared to baseline within the past three years or a documented positive methacholine or histamine bronchoprovocation test according to local guidelines with PC_20 ≤ 8 mg/mL or PD_20 ≤ 7.8 µmol within the past three years
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E.4 | Principal exclusion criteria |
1.Known or suspected allergy to trial products or related products 2.Previous participation in this trial. Participation is defined as randomised 3.Received an investigational drug within the last 4 weeks 4.Previous treatment with inhaled insulin other than AERx for a total of more than seven days 5.Pregnant or positive pregnancy test at screening, nursing mother, or unwillingness to use adequate contraception. Appropriate methods are: diaphragm, condom (by the partner), intrauterine device in place for the last three months before trial start, sponge, cap with spermicide, contraceptive patch, approved hormonal implant (i.e. Norplant), oral contraceptives (taken without difficulty for the last three months before trial start) post menopausal state or sterilisation or as required by local regulations 6.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-inhaled tobacco products 7. Chest X-ray with pulmonary clinically significant abnormalities (excluding changes due to asthma) as evaluated by a radiologist 8. Diagnosis of an upper or lower respiratory tract infection within three weeks prior to screening 9.Current acute or chronic pulmonary disease (excluding mild intermittent to moderate persistent asthma) 10. Clinical diagnosis of severe persistent asthma according to NAEPP guidelines hospitalisation in the previous year, as judged by the Investigator 11.Positive screening for hepatitis B antigen or hepatitis C antibody 12.Positive screening for human immunodeficiency virus (HIV) 13.Clinically significant, active (or over the past 12 months) disease of the cardiovascular, gastrointestinal, neurological, renal (creatinine ≥ 2 mg/dL [≥ 180 µmol/L], genitourinary or haematological systems 14.Sitting diastolic blood pressure (BP) ≥ 100 mmHg and/or systolic ≥180 mmHg) 15.Proliferative retinopathy requiring acute treatment or maculopathy requiring acute treatment 16.Total daily insulin dosage > 100 IU or U per day 17.History of hypoglycaemia unawareness and/or recurrent severe hypoglycaemia with more than two severe episodes in the past year 18.Impaired liver function, defined as screening aspartate aminotransferase or alanine aminotransferase ≥ 2.5 times upper normal range (one retest analysed at the central laboratory within one week is permitted with the last sample being conclusive) 19.History of any illness that, in the opinion of the Investigator, might confound the results of the trial or pose additional risk in administering study drug to the subject 20.Current addiction to alcohol or substances of abuse as determined by the Investigator 21.Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation in the study 22.Any conditions that the Investigator judges would interfere with trial participation or evaluation of the results
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in PFTs: FEV_1, FVC, FRC, RV, TLC, and D_L,CO as percent of predicted value from baseline (Visit 2) to 52 weeks of treatment Frequency of asthma exacerbations during 52 weeks of treatment Frequency of night-time awakenings due to asthma during 52 weeks of treatment Frequency and doses of asthma medication during 52 weeks of treatment Changes in X-ray from baseline (Visit 2) to 52 weeks of treatment
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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 | No |
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 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
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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 | 1 |
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 years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |