E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study is focused on asthma bronchiale and chronic obstructive pulmonary disease COPD). |
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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 | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 | 10010952 |
E.1.2 | Term | COPD |
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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 |
Primary: To evaluate the amount of drug deposited within the lungs (intrapulmonary drug deposition relative to the nominal dose, DL, N) in healthy volunteers, asthmatic and COPD patients.
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E.2.2 | Secondary objectives of the trial |
Secondary: •To evaluate the intrapulmonary distribution and the extrathoracic deposition •To evaluate Formoterol, BDP and B17MP pharmacokinetics. •To evaluate the efficacy by lung function assessment
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria Healthy volunteers: 1.Males and females without childbearing potential aged 21-65 years; 2.Ability to use the NEXT(TM)DPI; 3.Body Mass Index (BMI) between 18.0 and 28.0 kg/m2; 4.Non- or ex-smokers who smoked < 5 pack years (pack-years = the number of cigarette packs per day times the number of years e.g. < 20 cigarettes per day for 5 years and 40 cigarettes per day for 2.5 years) and stopped smoking > 1 year; 5.Good physical and mental status, determined on the basis of the medical history and a general clinical examination; 6.Normal blood pressure and heart rate (100 ≤ SBP ≤ 150; 45 ≤ DBP ≤90; 40 ≤ HR ≤ 100); 7.Electrocardiogram (ECG) (12 lead) with computerized protocol interpretation considered as normal (120 ms ≤ PR ≤ 220 ms, QRS ≤ 120 ms, QTc ≤ 450 ms). Minor deviations are acceptable provided the at they are not judged clinically significant by the investigator. 8.Results of laboratory tests within the normal ranges. Minor deviations are acceptable provided that they are not judged clinically significant by the investigator. 9.Understanding of the study and agreement to give written informed consent before the first selection procedure
Patients with Asthma: 1.Males and females (without childbearing potential) asthma patients aged 21-65 years; 2.Ability to use the NEXT(TM)DPI; 3.Body Mass Index (BMI) between 18.0 and 28.0 kg/m2; 4.Non- or ex-smokers who smoked < 5 pack years (e.g. < 20 cigarettes per day for 5 years and 40 cigarettes per day for 2.5 years) and stopped smoking > 1 year; 5.Normal blood pressure and heart rate (100 ≤ SBP ≤ 150; 45 ≤ DBP ≤90; 40 ≤ HR ≤ 100); 6.ECG (12 lead) with computerized protocol interpretation considered as normal (120 ms ≤ PR ≤ 220 ms, QRS ≤ 120 ms, QTc ≤ 450 ms). Minor deviations are acceptable provided that they are not judged clinically significant by the investigator. 7.FEV1 ≥ 30% and < 80% of predicted for the patient’s normal value (according to the predicted value for spirometric function, European Coal and Steel Community values [2]) measured at least 8 hours after the last use of short-acting β2-agonist bronchodilators or short-acting anticholinergics, 72 hours after the last use of long-acting β2-agonist bronchodilators and 72 hours after the last use of long-acting anticholinergics; 8.Reversibility of FEV1 ≥ 12% and at least 200 ml of the initial value 15 minutes after inhalation of 200 µg Salbutamol within the screening period; 9.In good health on the basis of a medical history, physical examination, clinical laboratory studies and ECG with the exception of asthma; 10.Understanding of the study and agreement to give written informed consent before the first selection procedure.
Patients with COPD: 1.Males and females without childbearing potential aged 40 – 70 years 2.Ability to use the NEXT(TM)DPI; 3.Body Mass Index (BMI) between 18.0 and 30.0 kg/m2; 4.Normal blood pressure and heart rate (100 ≤ SBP ≤ 150; 45 ≤ DBP ≤90; 40 ≤ HR ≤ 100); 5.ECG (12 lead) with computerized protocol interpretation considered as normal (120 ms ≤ PR ≤ 220 ms, QRS≤ 120 ms, QTc≤ 450 ms). Minor deviations are acceptable provided that they are not judged clinically significant by the investigator; 6.Stable COPD within the past 4 weeks; 7.Post bronchodilator FEV1 between 30% and 50% predicted values (30% ≤ FEV1 < 50%) documented at screening visit ; 8.Post bronchodilator FEV1/Forced Vital Capacity (FEV1/FVC) 0.70 (absolute value) documented at screening visit; 9.Minimum smoking history of 10 pack-years (e.g. < 20 cigarettes per day for 10 years and 40 cigarettes per day for 5 years); 10.Understanding of the study and agreement to give written informed consent before the first selection procedure.
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E.4 | Principal exclusion criteria |
Exclusion criteria All subjects: 1.Blood donation (equal or more than 450 ml) or blood loss less than 8 weeks before inhalation of the study medication; 2.Positive HIV1 or HIV2 serology; 3.Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C; 4.Unsuitable veins for repeated venipuncture; 5.Female patients: pregnant, positive pregnancy test, lactating mother or lack of efficient contraception (according to CPMP/ICH 286/95 note 3 1). Postmenopausal women < 1 year must have efficient contraception; 6.History of substance abuse or drug abuse within 12 months or with a positive urine drug screen; 7.Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation; 8.Clinically significant and uncontrolled cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol; 9.Participation in another clinical trial less than 8 weeks prior to inhalation of the study medication; participation in study using radioactive material within 1 calendar year; 10.Known sensitivity to Formoterol or Beclometasone or any of the excipients contained in any of the formulations used in the trial; 11.Enzyme-inducing or inhibiting drugs taken within 2 months before the inhalation of the study medication. 12.Concomitant severe diseases or diseases which are contra indications for the use of inhaled ß2-agonist or steroids; 13.Use of any prescription drug for which concomitant beta-agonist or steroid administration are contraindicated; 14.History of significant sensitivity, allergy or intolerance to study drug formulation ingredients; 15.Recent relevant infectious disease (less than two months); 16.Flu vaccination within 4 weeks prior to the screening visit; 17.Other vaccination within 4 weeks prior to the screening visit; 18.Subjects unlikely to comply with the study protocol or unable to understand the nature and scope of the study but also the possible benefits or unwanted effects of the study treatments;
Additional exclusion criteria for healthy volunteers 1.Lung function measurements outside normal limits (Normal values: FEV1/FVC > 0.70 (absolute value) and FEV1 and FVC > 80% for the European Community for Coal and Steel 1993 predicted values) or other standard values for healthy volunteers;
Additional exclusion criteria for patients with Asthma: 1.Use of systemic steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 6 months; 2.Life-threatening/unstable respiratory status including upper or lower respiratory tract infection, within the previous 30 days; 3.Requirement of continuous supplemental oxygen therapy; the use of supplemental oxygen not exceeding 2 l/min, at night time only and/or only during exercise is allowed; 4.Change in dose or type of any medications for asthma within 4 weeks prior to the screening visit; 5.Asthma exacerbation within the 4 weeks prior to inclusion.
Additional exclusion criteria for patients with COPD: 1.Use of systemic steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 6 months; 2.Life-threatening/unstable respiratory status including upper or lower respiratory tract infection, within the previous 30 days; 3.Requirement of continuous supplemental oxygen therapy; the use of supplemental oxygen not exceeding 2 l/min, at night time only and/or only during exercise is allowed; 4.Change in dose or type of any medications for COPD within 4 weeks prior to the screening visit; 5.COPD exacerbation within the 4 weeks prior to inclusion; 6.History of asthma or any chronic respiratory diseases other than COPD.
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E.5 End points |
E.5.1 | Primary end point(s) |
Intrapulmonary lung deposition (DL, N) expressed as % of nominal dose |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
lung deposition measurement |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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End of the trial: follow up phone call 7 days after visit 2a (described in protocol sections 6.12 and 7.1.4) |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |