Clinical trial NCT02126839: A Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler in Pediatric Asthmatics
Official title: A Three-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler (MDPI) Relative to Placebo in Pediatric Asthmatics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-30
Enrollment: 186
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is to evaluate the chronic-dose efficacy and the safety of Albuterol MDPI compared to placebo in pediatric participants with asthma.


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 premenarchal female 4-11 years of age, inclusive, as of the screening visit (SV)
3. Has a documented physician diagnosis of asthma per the EPR-3 Guidelines of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the SV
4. Has the ability to perform spirometry reproducibly consistent with ATS guidelines and protocol-specific guidelines
5. Has FEV1 50-95% predicted for age, height and gender at the SV following a minimum 6-hour period without β2-agonist use. (Note: Predicted values of 49.50-49.99% may be rounded up to 50% and values of 95.01-95.49% may be rounded down to 95%.)
6. Demonstrated reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol. (Note: Reversibility values of 14.50-14.99% may be rounded up to 15%.)
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), or inhaled cromones, and/or on short-acting β2-agonists (SABA); as needed SABA alone is acceptable. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the SV and should 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. Can tolerate the withdrawal of applicable medications for qualification at screening
10. Otherwise in general good health, defined as free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the trial, and with a clinically acceptable 6-month medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs
11. Parents consenting are capable of understanding the requirements, risks and benefits of study participation, and, as judged by the investigator, capable of giving informed consent and being compliant with all study requirements (eg, visits, record-keeping)
12. The patient is able to correctly use the MDPI device, either alone or with assistance by a parent/guardian.

Exclusion Criteria

1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (eg, lactose, ethanol)
2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the SV 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) that has not resolved within 4 weeks preceding the SV
5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A patient must not have had any hospitalization for asthma within 6 months prior to the SV.
6. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the SV must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.
7. 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
8. Use of any prohibited concomitant medications within the washout prescribed per protocol prior to study visits
9. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol as described in the protocol
10. The dosage of any required LTM, ICS, or inhaled cromones, has not been stable for at least 4 weeks. Intranasal corticosteroid and/or cromones have not been stable for at least two weeks prior to the SV. Allowed corticosteroid, LTM, and cromone asthma and allergy medications should be continued at the same doses during the conduct of the study.
11. Presence of any non-asthmatic acute or chronic condition, including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis, clinically significant cardiovascular disease (including but not limited to cardiac arrhythmias and uncontrolled hypertension), clinically significant hepatic, renal, or endocrine dysfunction, stroke, uncontrolled diabetes mellitus, hyperthyroidism, convulsive disorder, and malignancy other than basal cell carcinoma. Significant is defined as any condition that, in the opinion of the investigator, would put the safety of the patient at risk through participation, or which could affect the safety or efficacy analyses
12. Any other medical or psychological condition that in the investigator's opinion should preclude study enrollment
13. Previous participation (received MDPI study medication) in an Albuterol MDPI study
14. Study participation by clinical investigator site employees and/or their immediate relatives
15. Study participation by related or non-related individuals living in the same household, ie, only one subject per household may participate in the study at the same time.
16. Require continuous treatment with β-blockers, MAO inhibitors, tricyclic antidepressants, anticholinergics, and/or systemic corticosteroids
17. Treated with oral or injectable corticosteroids within the 6 weeks prior to SV
18. Hospitalization for acute asthma exacerbation \>2 times in 12 months prior to screening and/or received emergency room treatment other than nebulized albuterol or been hospitalized for asthma exacerbations within 6 months prior to SV

Primary outcomes:
measure: Baseline Adjusted Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) Area Under The Concentration Time Curve Up From Time Zero up to 6 Hours (AUC0-6) Over 3 Weeks
timeFrame: 30 ±5 and 5 ±2 minutes prior to dosing, and at 5 ±2, 15 ±5, 30 ±5, 45 ±5, 60 ±10, 120 ±10, 240 ±10, and 360 ±10 minutes after completion of dosing on Days 1 and 22
Secondary outcomes:
measure: Baseline Adjusted Peak Expiratory Flow (PEF) Area Under The Concentration Time Curve Up From Time Zero up to 6 Hours (AUC0-6) Over 3 Weeks
timeFrame: 30 ±5 and 5 ±2 minutes prior to dosing, and at 5 ±2, 15 ±5, 30 ±5, 45 ±5, 60 ±10, 120 ±10, 240 ±10, and 360 ±10 minutes after completion of dosing on Days 1 and 22
measure: Summary of Participants With Adverse Events
timeFrame: 6 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 12496
state: Alabama
city: Mobile
country: United States
facility: Teva Investigational Site 12500
state: Alabama
city: Little Rock
country: United States
facility: Teva Investigational Site 12481
state: Alaska
city: Anaheim
country: United States
facility: Teva Investigational Site 12515
state: California
city: Costa Mesa
country: United States
facility: Teva Investigational Site 12505
state: California
city: Huntington Beach
country: United States
facility: Teva Investigational Site 12476
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 12519
state: California
city: Mission Viejo
country: United States
facility: Teva Investigational Site 12484
state: California
city: Riverside
country: United States
facility: Teva Investigational Site 12510
state: California
city: Rolling Hills Estates
country: United States
facility: Teva Investigational Site 12483
state: California
city: Sacramento
country: United States
facility: Teva Investigational Site 12511
state: California
city: Stockton
country: United States
facility: Teva Investigational Site 12485
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 12512
state: Colorado
city: Gainesville
country: United States
facility: Teva Investigational Site 12522
state: Florida
city: Hollywood
country: United States
facility: Teva Investigational Site 12535
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 12526
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 12516
state: Florida
city: Tamarac
country: United States
facility: Teva Investigational Site 12517
state: Florida
city: Vero Beach
country: United States
facility: Teva Investigational Site 12527
state: Florida
city: Winter Park
country: United States
facility: Teva Investigational Site 12513
state: Florida
city: Gainesville
country: United States
facility: Teva Investigational Site 12486
state: Georgia
city: Lawrenceville
country: United States
facility: Teva Investigational Site 12497
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 12480
state: Georgia
city: Shiloh
country: United States
facility: Teva Investigational Site 12508
state: Illinois
city: Iowa City
country: United States
facility: Teva Investigational Site 12518
state: Iowa
city: Covington
country: United States
facility: Teva Investigational Site 12523
state: Louisiana
city: Warrensburg
country: United States
facility: Teva Investigational Site 12495
state: Missouri
city: Northfield
country: United States
facility: Teva Investigational Site 12509
state: New Jersey
city: Brooklyn
country: United States
facility: Teva Investigational Site 12524
state: New York
city: Raleigh
country: United States
facility: Teva Investigational Site 12473
state: North Carolina
city: Cincinnati
country: United States
facility: Teva Investigational Site 12477
state: Ohio
city: Cleveland
country: United States
facility: Teva Investigational Site 12525
state: Ohio
city: Middleburg Heights
country: United States
facility: Teva Investigational Site 12502
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 12478
state: Oklahoma
city: Oklahoma City
country: United States
facility: Teva Investigational Site 12487
state: Oklahoma
city: Oklahoma City
country: United States
facility: Teva Investigational Site 12506
state: Oklahoma
city: Tulsa
country: United States
facility: Teva Investigational Site 12492
state: Oklahoma
city: Gresham
country: United States
facility: Teva Investigational Site 12507
state: Oregon
city: Normal
country: United States
facility: Teva Investigational Site 12501
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Teva Investigational Site 12493
state: Pennsylvania
city: Upland
country: United States
facility: Teva Investigational Site 12488
state: Pennsylvania
city: Greenville
country: United States
facility: Teva Investigational Site 12514
state: South Carolina
city: Orangeburg
country: United States
facility: Teva Investigational Site 12474
state: South Carolina
city: Spartanburg
country: United States
facility: Teva Investigational Site 12479
state: South Carolina
city: Boerne
country: United States
facility: Teva Investigational Site 12489
state: Texas
city: Waco
country: United States
facility: Teva Investigational Site 12475
state: Texas
city: Burke
country: United States
facility: Teva Investigational Site 12491
state: Virginia
city: Charlottesville
country: United States
facility: Teva Investigational Site 12504
state: Virginia
city: Richmond
country: United States
facility: Teva Investigational Site 12482
state: Virginia
city: Richmond
country: United States
facility: Teva Investigational Site 12498
state: Virginia
city: Spokane
country: United States
facility: Teva Investigational Site 12490
state: Washington
city: Papillion
country: Thailand
facility: Teva Investigational Site 12533
state: NE
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Sponsor's Medical Expert, MD
role: STUDY_DIRECTOR
References:
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.