| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| moderate or severe asthma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| 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 aim of the trial is to investigate whether long-term treatment with 320 and 640μg ciclesonide/day for one year improves asthma control in subjects with lack of asthma control while on 160μg ciclesonide/day.
Additionally, the trial will provide further data on the long-term safety and tolerability of ciclesonide. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent was provided,
2. Age between 18 and 70 years,
3. History of persistent bronchial asthma (GINA 2009) for at least 6 months
4. Current treatment with an ICS at a stable dose in the dose range of 200-1000μg FP/day or equivalent for a minimum of 12 weeks,
5. Under the current ICS pre-treatment an ACQ score as defined below:
ICS pre-treatment dose: low dose ICS (FP 200 – 250μg/day or equivalent); ACQ at start of baseline minimum 2
ICS pre-treatment dose: medium or high dose ICS (FP >250 – 1000μg/day or equivalent); ACQ at start of baseline between 0.75 and < 2
6. Good inhalation technique
7. Certified asthma training has been completed
|
|
| E.4 | Principal exclusion criteria |
a) Diseases and health status:
1. Clinically relevant abnormal laboratory values and vital signs suggesting an unknown underlying disease and requiring further clinical evaluation (as assessed by the investigator),
2. Any malignant disease (other than basal or squamous cell carcinoma) within 5 years before trial start,
3. Other concomitant severe diseases (e.g. hepatitis C, AIDS),
4. Diseases which are contraindications for the use of ICS (e. g. active or inactive pulmonary tuberculosis or relevant fungal, bacterial or viral infections of the lower respiratory tract demanding specific treatment),
5. The subject suffers from Chronic Obstructive Pulmonary Disease (COPD) and/or other relevant lung diseases associated with impaired lung function,
6. Severe psychiatric or neurological disorders,
7. Current or previous smoking with more than a 10 pack-years.
b) Medications:
9. Use of other drugs not allowed,
10. Washout times of drugs defined cannot be adhered to,
11. Known or suspected hypersensitivity to inhaled steroids or to the other excipients of the ciclesonide MDIs,
12. Intolerance to short-acting beta agonists and/or to the excipients of salbutalmol MDI,
13. Start of immunotherapy either during the subject’s participation in the trial or less than three months prior to enrolment, or changes in the regimen during the trial period.
c) Common criteria:
14. Participation in another clinical trial with an investigational drug or device within 30 days before inclusion in this trial and during the present trial,
15. Previous participation in this trial,
16. Enrolment of the investigator, his/her family members and employees at the site,
17. Known or suspected non-compliance, alcohol or drug abuse,
18. Inability to follow the procedures of the trial, e.g. due to language problems, psychological disorders or dementia,
19. Planned relocation during the trial period to an area outside the operating distance of the investigator,
20. Planned prolonged absence (e.g. holiday) in which the subject cannot be reached via phone.
For females of childbearing potential, i.e. not postmenopausal (less than 12 months after last menstruation) or not surgically sterile:
21. A positive pregnancy test before the first administration of investigational medicinal product,
22. No acceptable contraceptive method. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intra-uterine devices (IUDs with copper or progestogen), sexual abstinence or vasectomised partner. For subjects using a hormonal contraceptive method, there are no known interactions with ciclesonide,
23. Intention to become pregnant during the course of the trial,
24. Breast feeding,
25. the person concerned has not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Difference from last measurement to baseline in ACQ for the comparison 640μg ciclesonide/day vs. 160μg ciclesonide/day:
In case that the comparison 640μg ciclesonide/day vs.160μg ciclesonide/day is statistically significant the comparison 320μg ciclesonide/day vs. 160μg ciclesonide/day will be tested subsequently (fixed sequence approach).
Subgroup analyses will be performed for pre-trial ICS dose, baseline ACQ and body mass index. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the treatment period visits will generally take place in 6-week intervals, except for the first visit (T4) which will take place after 4 weeks (visits T0, T4, T10, T16, T22, T28, T34, T40, T46 and T52),
If needed, safety follow-up (30 days after T52/Tend).
During the treatment period asthma control will be assessed in weekly intervals by means of the ACQ. |
|
| E.5.2 | Secondary end point(s) |
• Time course for ACQ score,
• Number of weeks with well-controlled asthma (i.e. ACQ score ≤ 0.75),
• Time to achieve well-controlled asthma for the first time,
• Percent of subjects with well-controlled asthma at each week of the treatment period,
• Number/percent of subjects with well-controlled asthma at the end of the trial,
• Number/percent of subjects with an ACQ improvement by at least 0.5 at the trial visits and at T52/Tend, respectively,
• Time to achieve an ACQ improvement by 0.5 for the first time,
• Proportion of subjects below an ACQ cut-off point of 0.5, 0.75, 1.0, 1.25 and 1.5, at the trial visits and at T52/Tend, respectively,
• Weighted mean weekly ACQ score,
• Percentage of weeks with asthma control defined as ACQ below the cut-off points of 0,5, 0.75, 1.0, 1.25 and 1.5,
• Time to an exacerbation and exacerbation rates.
Safety
• AEs,
• Physical examination,
• Vital signs,
• Standard laboratory values. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
During the treatment period visits will generally take place in 6-week intervals, except for the first visit (T4) which will take place after 4 weeks (visits T0, T4, T10, T16, T22, T28, T34, T40, T46 and T52),
If needed, safety follow-up (30 days after T52/Tend).
During the treatment period asthma control will be assessed in weekly intervals by means of the ACQ. |
|
| 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 | Yes |
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | No |
| 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.8.6 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 | No |
| 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 |
| Argentina |
| Brazil |
| Germany |
| Israel |
| Russian Federation |
|
| 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
|
| The end-of-trial is defined as the date of database hard lock. |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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