| 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 | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| 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 study is to evaluate the bronchodilating effects of 3 doses of formoterol given in combination with budesonide as Symbicort pMDI in a population of asthmatic children demonstrated to be stable on a medium dose range of ICS therapy. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to:
• evaluate the bronchodilating effect of Foradil Aerolizer (formoterol fumarate
inhalation powder; Schering) 12 μg
• determine the systemic exposure to formoterol following administration of formoterol 2.25 μg, 4.5 μg, and 9 μg, given in combination with budesonide as Symbicort pMDI or Foradil Aerolizer 12 μg. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provision of signed and dated informed consent prior to conducting any studyspecific procedures.
2. Is between the ages of 6 and <12 years (not having reached his/her 12th birthday at the time of Visit 1).
3. Has a documented clinical diagnosis of asthma as defined by the American
Thoracic Society (ATS, ie, “a disease characterized by increased responsiveness of
the trachea and bronchi to various stimuli and manifested by widespread narrowing
of the airway that changes in severity either spontaneously or as a result of
therapy”) for at least 6 months prior to Visit 1.
4. Has a FEV1 measured at least 6 hours after the last dose of inhaled, short-acting β2-agonist (SABA) and at least 48 hours after the last dose of inhaled LABA of ≥60%
and ≤85% of predicted normal. Polgar predicted normal standards will be used for
all patients. If the patient is taking a fixed combination of ICS and LABA, the patient is to be placed on a comparable dose of ICS without the addition of a LABA
at least 48 hours prior to spirometry testing.
5. Demonstrated reversibility of FEV1 of ≥15% from pre-albuterol level within 15 to
30 minutes after administration of a standard dose of albuterol at Visit 2 (albuterol
MDI, 90 μg per inhalation, 2 to 4 actuations, with or without a spacer, or up to
2.5 mg of nebulized albuterol). Patients can return to the clinic once within 7 days
for a 2nd attempt at reversibility if the first attempt was ≥12 % but <15%. This 2nd
attempt must be done in the morning. Until the reversibility criterion is met, the
patient must not be withdrawn from his/her usual ICS and must not be dispensed
run-in medication, study reliever medication, or patient notebook and diary. The
run-in period cannot start until after the FEV1 and reversibility criteria have been
met.
6. Has required and received treatment with a consistent daily dose of ICS within the
corresponding dose range listed below for at least 4 weeks prior to Visit 1. If the
patient is not under the care of the investigator, documentation of ICS use by
pharmacy records or copies of the prescribing Health Care Practitioner’s records are
required, to verify ICS use.
− Beclomethasone dipropionate HFA pMDI: 160 - 320 μg/day
− Budesonide: 360 - 540 μg/day
− Budesonide (nebulized): 1000 μg/day
− Flunisolide: 1000 - 1250 μg/day
− Flunisolide HFA: 320 μg/day
− Fluticasone 176 - 352 μg/day (HFA pMDI) or 200-400 μg/day (Diskus)
− Triamcinolone acetonide: ≥600 - 900 μg/day
− Ciclesonide: 320 - 480 μg/day
− Mometasone: 440 μg/day
Note: Other non-steroidal asthma medications (eg, leukotriene modifiers, mast
cell stabilizers) could have been used in combination with any of the above and
would not impact a patient’s eligibility. After providing written informed
consent for withdrawal of medication and at least 48 hours prior to spirometry
testing, potential patients maintained on a fixed combination of ICS and LABA
should be switched to a comparable dose of ICS without the addition of a longterm
β2-agonist. This change will not be considered a change in the dose of
maintenance ICS.
7. If receiving inhalant allergen immunotherapy, the patient must have been on a
stable maintenance regimen for at least 6 weeks and is expected to remain on
immunotherapy throughout the study.
Randomization criteria (Visit 3)
1. Has discontinued use of all asthma medications, including all formulations of
β2-agonists, following Visit 2 (or since meeting the FEV1/reversibility criteria, if
met after Visit 2) and used only the open-label run-in medication and reliever
medication provided since Visit 2.
Has a pre-dose morning clinic FEV1 measured at least 6 hours after the last dose of
inhaled SABA with <12% variation from the pre-dose, baseline FEV1(L)
measurement obtained at the visit where the patient showed reversibility of at least
15%. |
|
| E.4 | Principal exclusion criteria |
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Has been hospitalized for >24 hours at least once or has required emergency
treatment more than once in an emergency department (or equivalent) for acute
deterioration of asthma during the 6 months prior to Visit 1.
2. Has required treatment with systemic corticosteroids (eg, oral, parenteral, or rectal) for any reason within the 12 weeks prior to Visit 1.
3. Has participated in another investigational drug study during the 4 weeks prior to
Visit 1.
4. Has participated in a prior Symbicort clinical study within the previous 12 months.
5. Is receiving treatment with a β-blocker (including eye drops).
6. Has taken Xolair®, or any other monoclonal or polyclonal antibody therapy, for any
reason within the 6 months prior to Visit 2.
7. Positive pregnancy test at any time during the study.
8. Has any significant disease or disorder, which, in the opinion of the investigator,
may either put the patient at risk because of participation in the study, or influence
the results of the study, or the patient’s ability to participate in the study.
9. Has a planned hospitalization during the study.
10. Has any clinically relevant abnormal findings on physical examination or vital signs
at baseline visit, which, in the opinion of the investigator, may put the patient at risk
because of his/her participation in the study.
11. Has known or suspected hypersensitivity to study medications and/or their
excipients.
Exclusion criteria at randomization (Visit 3)
1. Has been treated with systemic corticosteroids (eg, oral, parenteral, or rectal) for
any reason during the run-in period or at time of Visit 3.
2. Has been hospitalized for >24 hours or has required emergency treatment in an
emergency department (or equivalent) for acute deterioration of asthma during the
run-in period.
3. Has a respiratory infection or other viral/bacterial illness or is recovering from such
an illness at the time of Visit 3, which, in the investigator’s opinion, will interfere
with the patient’s lung function and/or ability to perform serial spirometry. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Outcome variable(s):
• Efficacy
- The primary efficacy variable will be AUC0-12 for FEV1.
- The secondary efficacy variables are FEV1 at 12 hours after study medication
inhalation and the maximal FEV1 for the 12-hour study period.
• Pharmacokinetics
- 12-hour urine collection to measure unchanged formoterol
• Safety
- Incidence of adverse events, discontinuations due to adverse events, serious
adverse events |
|
| 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) | 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| 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 | 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
|
| The last visit of the last patient undergoing the study |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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