Clinical trial NCT01899144: Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® Hydrofluoroalkane (HFA) in Pediatric Patients
Official title: A Single-Dose, Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Five-Period Crossover, Dose-Ranging Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® HFA in Pediatric Patients With Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Albuterol Spiromax
ProAir HFA
albuterol sulfate
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-15
Enrollment: 61
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, double-dummy, placebo-controlled, single-dose, 5-treatment, 5-period, 5-way crossover study in pediatric patients with persistent asthma. The primary purpose of this study is to compare the efficacy and safety of Albuterol Spiromax with that of ProAir HFA in pediatric asthma patients at 2 delivered dose levels equivalent to 90 mcg and 180 mcg of albuterol base.

Detailed description: The study consists of a screening visit (SV) followed by up to 16 days by a treatment period comprising 5 visits (TV1-TV5). The treatment period visits will each be separated by a washout period lasting 2-7 days. During each treatment period visit, the forced expiratory volume in 1 second (FEV1) will be determined at 30 minutes and again immediately prior to the commencement of study medication administration, and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after completion of study medication administration.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study related procedure
2. Male or pre-menarchal female 4-11 years of age, inclusive, as of the screening visit
3. Has a documented physician diagnosis of persistent asthma of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the screening visit. The asthma diagnosis must be in accordance with the National Asthma Education and Prevention Program Guidelines Expert Panel Report 3 (EPR3)
4. Has the ability to self-perform spirometry reproducibly per American Thoracic Society (ATS) guidelines
5. Has forced expiratory volume in 1 second (FEV1) 60-90% predicted for age, height, and gender at the screening visit based on the pediatric population standards as per protocol.

   Notes: (1) Predicted values of 59.50-59.99% may be rounded up to 60% and 90.01-90.49% rounded down to 90%. (2) Patients who at the screening visit fail to meet the predicted spirometry values for study entry may be allowed a single attempt to re-qualify on another day, but they must re-qualify no later than 16 days following the first attempt.
6. Demonstrates reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), inhaled cromones, or on β2-agonists alone as needed. The Inhaled corticosteroid (ICS), LTM, and cromone doses must have been stable for at least 4 weeks prior to the screening visit and are expected to be maintained for the duration of the study
7. Is maintained on low-dose inhaled corticosteroids (\[ICS\], less than or equal to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), inhaled cromones, or on β2-agonists alone as needed. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the screening visit and are expected to be maintained for the duration of the study
8. Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter
9. Has the ability to demonstrate acceptable and reproducible inhalation technique with the Spiromax and metered dose inhaler (MDI) devices

   * Other inclusion criteria apply.

Exclusion Criteria:

1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (lactose, ethanol, etc.)
2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the screening visit or planned participation in another investigational drug trial at any time during this trial
3. History of severe milk protein allergy
4. History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc.) that has not resolved within 4 weeks preceding the screening visit
5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the screening visit. A patient must not have had any hospitalization for asthma within 6 months prior to the screening visit.
6. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures
7. Use of any prohibited concomitant medications within the washout period prescribed per protocol prior to the screening visit.
8. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol
9. The dosage of any required intranasal corticosteroid and/or cromone has not been stable for at least 2 weeks prior to the screening visit.
10. Treated with oral or injectable corticosteroids within the 6 weeks before the screening visit.
11. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the screening visit must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.

Primary outcomes:
measure: Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose
timeFrame: Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati
Secondary outcomes:
measure: Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6)
timeFrame: Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati
measure: Participants With Treatment-Emergent Adverse Events
timeFrame: Day 1 up to Day 35
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 10598
state: Alabama
city: Little Rock
country: United States
facility: Teva Investigational Site 10593
state: Alaska
city: Costa Mesa
country: United States
facility: Teva Investigational Site 10610
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 10582
state: California
city: Orange
country: United States
facility: Teva Investigational Site 10606
state: California
city: San Jose
country: United States
facility: Teva Investigational Site 10597
state: California
city: Jacksonville
country: United States
facility: Teva Investigational Site 10596
state: Florida
city: Lawrenceville
country: United States
facility: Teva Investigational Site 10599
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 10580
state: Georgia
city: Normal
country: United States
facility: Teva Investigational Site 10592
state: Illinois
city: Missoula
country: United States
facility: Teva Investigational Site 10602
state: Montana
city: Raleigh
country: United States
facility: Teva Investigational Site 10578
state: North Carolina
city: Oklahoma City
country: United States
facility: Teva Investigational Site 10577
state: Oklahoma
city: Medford
country: United States
facility: Teva Investigational Site 10589
state: Oregon
city: Portland
country: United States
facility: Teva Investigational Site 10604
state: Oregon
city: Charleston
country: United States
facility: Teva Investigational Site 10591
state: South Carolina
city: Orangeburg
country: United States
facility: Teva Investigational Site 10609
state: South Carolina
city: Spartanburg
country: United States
facility: Teva Investigational Site 10579
state: South Carolina
city: Boerne
country: United States
facility: Teva Investigational Site 10588
state: Texas
city: New Braunfels
country: United States
facility: Teva Investigational Site 10605
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 10583
state: Texas
city: Waco
country: United States
facility: Teva Investigational Site 10576
state: Texas
Study officials:
References:
citation: Qaqundah PY, Taveras H, Iverson H, Shore P. Albuterol multidose dry powder inhaler and albuterol hydrofluoroalkane versus placebo in children with persistent asthma. Allergy Asthma Proc. 2016 Sep;37(5):350-8. doi: 10.2500/aap.2016.37.3986.
citation: Ratnayake A, Taveras H, Iverson H, Shore P. Pharmacokinetics and pharmacodynamics of albuterol multidose dry powder inhaler and albuterol hydrofluoroalkane in children with asthma. Allergy Asthma Proc. 2016 Sep;37(5):370-5. doi: 10.2500/aap.2016.37.3985. Epub 2016 Aug 12.