A double-blind, double-dummy, randomized, placebo- and active-controlled, three-way crossover study to evaluate the effect of Budesonide/Formoterol Spiromax® 80/4.5 mcg Inhalation Powder and Symbicort® Turbohaler® 100/6 mcg on the short-term lower leg growth rate in prepubescent children with persistent asthma.

• Conditions: Short term lower leg growth rate in prepubescent children with persistent asthma.; MedDRA version: 12.1Level: LLTClassification code 10003553Term: Asthma

• Registration Number: EUCTR2010-019082-29-DK
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-05
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Written informed consent signed and dated by both parents/guardians before conducting any study related procedure
2. Male and female prepubescent (Tanner stage 1) subjects aged 6 to 11 years, inclusive at the SV
3. Subjects must have a documented history and physician confirmed and documented diagnosis of asthma for at least 3 months before the SV
4. Subjects must be currently using inhaled ß2-agonists or inhaled corticosteroids in doses of Budesonide DPI = 400 mcg or Budesonide MDI = 800 mcg daily or other ICS equipotent to these doses
5. Documented normal growth development (height between 3- and 97-percentiles according to standard growth charts)
6. Peak expiratory flow rate (PEF) and forced expiratory volume in 1 second (FEV1) is >80% of predicted values based on established values for individual subjects
7. Demonstrated satisfactory technique in the use of Spiromax and Turbohaler devices at the SV as outlined in Appendices 2 and 3 (of the protocol)
8. Willingness and ability to accurately complete subject diary with the assistance of their parents/guardians
9. Parents or legal guardians are capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the Investigator, capable of giving informed consent and complying with all study requirements (e.g. visits, daily diary completion).

RANDOMIZATION CRITERIA
1. No occurrence of an upper or lower respiratory tract infection during the Run-In Period
2. No asthma exacerbation, defined as any worsening of asthma requiring any treatment other than rescue medication. This includes requiring the use of systemic corticosteroids and/or emergency room visit or hospitalization
3. Normal visual oropharyngeal exam at the randomization visit (V1)
4. Subject continues to be in general good health, meeting the selection criteria.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects having entered puberty (Tanner stage >1)
2. History of life-threatening asthma (an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures)
3. A culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear within 3 days preceding the SV
4. Febrile illness with temperature > 39°C for more than five consecutive days within seven days of the SV
5. Major surgery requiring general anesthesia within seven days of the SV
6. Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV
7. Hospitalization due to asthma twice or more within 12 months prior to the SV or within 3 months of the SV
8. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular disease, hepatic disease, renal disease, hematological disease, neurological disease, pulmonary disease (including but not limited to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, or chronic obstructive pulmonary disease), immunologic disease, or malignancy
9. Current or prior (i.e., in the 4 weeks preceding the SV) use of high-dose ICS (>220 mcg/day of fluticasone propionate or equivalent ICS) for routine control of asthma
10. Continuous use of a long-acting ß2-agonist (inhaled or oral) for asthma symptoms
11. Known or suspected sensitivity to budesonide, formoterol, or any of the constituents of the dry powder inhalers
12. History of severe allergy to milk proteins
13. Clinical evidence of oral candidiasis at the SV
14. History or current presence of glaucoma or posterior subcapsular cataracts
15. Non-vaccinated or active infection with chickenpox or measles
16. Administration of systemic, oral, or depot corticosteroids within 12 weeks of the SV
17. Use of any oral or inhaled or injected asthma medication within 1 week of the SV (e.g., anticholinergics, cromolyn or nedocromil, theophylline compounds, except for study defined inhaled corticosteroids and inhaled short acting ß2-agonists
18. Treatment with any known potent CYP3A4 inhibitors within 4 weeks preceding the SV (e.g., ritonavir, ketoconazole, itraconzole)
19. Use of any medications that could affect the course of asthma, growth rate, or interact with study medications (e.g., anticonvulsants, ß-adrenergic blockers, intranasal steroids, and topical steroids)
20. Parent or legal guardian has an infirmity, disability, or geographical location which may impair study compliance (e.g., completion of daily diary, non-availability for study visits/procedures, non-compliance with study medication)
21. Participation in an investigational drug trial during 30 days preceding the SV
22. Subject is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Demonstrate non-inferiority of Budesonide/Formoterol Spiromax 80/4.5 mcg Inhalation Powder (BF Spiromax) relative to Symbicort Turbohaler 100/6 mcg (Symbicort Turbohaler) on change in growth rate of the right lower leg as measured by knemometry in prepubescent children with persistent asthma.;Secondary Objective: • Assess the safety and tolerability of BF Spiromax and Symbicort Turbohaler<br>• Assess the 24-hour urinary cortisol excretion during treatment with BF Spiromax relative to Symbicort Turbohaler in prepubescent children with persistent asthma<br>• Assess the change in growth rate of the right lower and 24-hour urinary cortisol excretion with BF Spiromax and Symbicort Turbohaler relative to placebo.;Primary end point(s): The primary efficacy endpoint is growth rate of the right lower leg as measured by knemometry after 2 weeks of randomized treatment.