E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
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 efficacy of beclomethasone dipropionate administered via BAI and MDI (80 or 160 mcg/day) compared with placebo treatment in pediatric patients 4 through 11 years of age with persistent asthma as assessed by the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) percent predicted forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 12 weeks (FEV1 AUEC 0-12wk). |
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E.2.2 | Secondary objectives of the trial |
1) to evaluate the efficacy of beclomethasone dipropionate treatment administered via BAI and MDI compared with placebo treatment in patients with persistent asthma 2) to evaluate the safety and tolerability of beclomethasone dipropionate treatment as assessed by the occurrence of treatment-emergent adverse events and vital signs assessments throughout the study; physical examination findings at the screening visit (SV) and the final treatment visit/treatment discontinuation visit (TV4/TdV); and oropharyngeal examination findings at every visit through TV4 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a1. Severity of disease: The patient has persistent asthma, with a forced expiratory volume in 1 second (FEV1) 40% to 90% of the value predicted for age, height, and sex at screening visit (SV). b1. Current asthma therapy: The patient is currently being treated with 1 of the following: - a stable daily dosage of an inhaled corticosteroid (ICS) in the range of 88-176 mcg/day of fluticasone propionate (or equivalent) for a minimum of 4 weeks (28 days) before SV - a stable daily dosage of non-corticosteroid therapy, including leukotriene modifiers, theophylline, chromones, or short-acting β2-agonists [SABAs] alone or in combination for a minimum of 4 weeks (28 days) before SV. Patients taking non-corticosteroid therapy will also need to meet uncontrolled asthma criteria before randomization - a daily dose of ICS plus a LABA (at a dose less than or equivalent to fluticasone propionate 100 mcg/salmeterol 50 mcg twice daily) may be allowed but the patient will be required to discontinue this therapy and start fluticasone propionate MDI (44 mcg, 2 inhalations twice daily, for a total daily dose of 176 mcg/day or equivalent for at least 7 days to no more than 30 days before SV c2. Reversibility of disease: The patient has demonstrated at least 12% reversibility of FEV1 within 30 minutes after 2-4 inhalations of albuterol/salbutamol hydrofluoroalkane (HFA) MDI (90 mcg ex-actuator) or equivalent at SV or on retesting. Patients aged 4-5 years who fail reversibility of FEV1 must demonstrate at least 12% reversibility of PEF after 2-4 inhalations of albuterol/salbutamol HFA MDI (90 mcg ex-actuator) or equivalent using the handheld peak flow meter. Nebulized albuterol/salbutamol at a total dose of 2.5 mg may be used at the investigator’s discretion. Reversibility values of 11.50-11.99 will be rounded to 12. A documented historical reversibility, including expiratory flow loops, of at least 12% to a beta-agonist in the previous 12 months before SV is acceptable for patients treated with ICS at baseline. Historical data is not acceptable for patients on non-corticosteroid therapy. d. Written informed consent must be signed and dated by parent/legal guardian and the written informed assent form must be signed and dated by the patient (as applicable, per local regulations) before any study-related procedures are conducted. e1. The patient is a male or female patient 4 through 11 years of age, inclusive, when informed consent/assent is signed (screening or prescreening visit, as applicable). f. Asthma diagnosis: The patient has a diagnosis of asthma as defined by the NIH. The asthma diagnosis has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in medication) for at least 30 days before SV. g1. The patient is able to perform acceptable and repeatable spirometry consistent with the ATS/ERS 2005 criteria h. The patient is able to perform peak expiratory flow (PEF) (with assistance from parents/guardians/caregivers, as needed) with a hand-held peak flow meter. i. The patient is able to use (with assistance from parents/guardians/caregivers, as needed) an MDI device without a spacer device and a BAI device. j. The patient is able to withhold (as judged by the investigator) his or her morning regimen of asthma medication (non-corticosteroid therapy, ICS, or study drug) and rescue medication (eg, albuterol/salbutamol hydrofluoroalkane [HFA] MDI [or equivalent]) for at least 6 hours before SV and the treatment visits in which spirometry will be conducted (SV, randomization visit [RV], treatment visit [TV] 1, TV2, TV3, and TV4). k. The patient is assessed as otherwise healthy, with clinically acceptable medical history, physical examination, and vital signs within the acceptable ranges for children with asthma as assessed by the investigator. l. Each patient/parent/guardian/caregiver is capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements. m. If female, and the patient has reached puberty and achieved menarche (as determined by the investigator), parents/guardians will be consulted to obtain permission to counsel the patient regarding the possible unknown risks associated with study medication during pregnancy. Eligible female patients of childbearing potential whom are known to be sexually active will be excluded. Additionally, a urine pregnancy test must be negative at the SV. |
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E.4 | Principal exclusion criteria |
a. The patient has a history of life-threatening asthma, defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, or hypoxic seizures. b. The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the patient’s last study-related visit (for eligible patients only, if applicable). Any patient becoming pregnant during the study will be withdrawn from the study. c. The patient has participated in any investigational drug study within the 30 days (starting at the final follow-up visit of that study) preceding SV (or prescreening visit, as applicable), or plans to participate in another investigational drug study at any time during this study. d. The patient has previously participated in a beclomethasone dipropionate BAI study as a randomized patient. e. The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation. f. The patient has been treated with any known strong cytochrome P450 (CYP) 3A4 inhibitors (eg, azole antifungals, ritonavir, clarithromycin) within 30 days before SV or plans to be treated with any strong CYP3A4 inhibitor during the study. g. The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before SV. h. The patient has used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco, as applicable). i. The patient has a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract (URI or LRI), sinus, or middle ear that has not resolved at least 2 weeks before SV. j. The patient has a history of alcohol or drug abuse within 2 years preceding SV, as applicable. k. The patient has had an asthma exacerbation requiring oral corticosteroids within 30 days before SV, or has had any hospitalization for asthma within 2 months before SV. l. Initiation or dose escalation of immunotherapy (administered by any route) is planned during the study period. However, patients who initiated immunotherapy 90 days or more before the screening visit (SV) and have been on a stable (maintenance) dose for 30 days or more may be considered for inclusion. m. The patient has used immunosuppressive medications within 4 weeks (28 days) before SV. n. The patient is unable to tolerate or unwilling to comply with the required washout periods and withholding of all applicable medications. o. The patient has untreated oral candidiasis at SV. Patients with clinical visual evidence of oral candidiasis who agree to receive treatment and comply with appropriate medical monitoring may enter the study. p. The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection. q. The patient is an immediate relative of an employee of the clinical investigational center. r. A member of the patient’s household is participating in the study at the same time. (However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened.) s1. The patient has a disease/condition that, in the medical judgment of the investigator, would put the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for this study is the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) percent predicted FEV1 AUEC 0-12wk. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary efficacy endpoint timeline is over the 12-week treatment period. |
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E.5.2 | Secondary end point(s) |
Secondary outcome variables are as follows: - change from baseline in weekly average of daily trough morning (pre-dose and pre-rescue bronchodilator) PEF over the 12-week treatment period - change from baseline in weekly average of daily evening PEF over the 12-week treatment period - change from baseline in the weekly average of total daily (24-hour) use of albuterol/salbutamol inhalation aerosol (number of inhalations) over weeks 1-12 - change from baseline in weekly average of the total daily asthma symptom score (the total daily asthma symptom score is the average of the daytime and nighttime scores) over weeks 1-12 - change from baseline in trough morning (pre-dose and pre-rescue bronchodilator) FEV1 over the 12-week treatment period - time to patient withdrawal due to meeting stopping criteria for worsening asthma during the 12-week treatment period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluations for all endpoints are over Weeks 1-12. |
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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 | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Croatia |
Lithuania |
Mexico |
Poland |
Romania |
Serbia |
Ukraine |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |