A Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler in Pediatric Asthmatics

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: ProAir HFA inhaler; Drug: Albuterol MDPI

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • NE
    • Papillion, NE, Thailand
      • Teva Investigational Site 12533
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Teva Investigational Site 12496
    • Mobile, Alabama, United States
      • Teva Investigational Site 12500
  • Alaska
    • Little Rock, Alaska, United States
      • Teva Investigational Site 12481
  • California
    • Anaheim, California, United States
      • Teva Investigational Site 12515
    • Costa Mesa, California, United States
      • Teva Investigational Site 12505
    • Huntington Beach, California, United States
      • Teva Investigational Site 12476
    • Los Angeles, California, United States
      • Teva Investigational Site 12519
    • Mission Viejo, California, United States
      • Teva Investigational Site 12484
    • Riverside, California, United States
      • Teva Investigational Site 12510
    • Rolling Hills Estates, California, United States
      • Teva Investigational Site 12483
    • Sacramento, California, United States
      • Teva Investigational Site 12511
    • Stockton, California, United States
      • Teva Investigational Site 12485
  • Colorado
    • Centennial, Colorado, United States
      • Teva Investigational Site 12512
  • Florida
    • Gainesville, Florida, United States
      • Teva Investigational Site 12522
    • Hollywood, Florida, United States
      • Teva Investigational Site 12535
    • Miami, Florida, United States
      • Teva Investigational Site 12526
    • Orlando, Florida, United States
      • Teva Investigational Site 12516
    • Tamarac, Florida, United States
      • Teva Investigational Site 12517
    • Vero Beach, Florida, United States
      • Teva Investigational Site 12527
    • Winter Park, Florida, United States
      • Teva Investigational Site 12513
  • Georgia
    • Gainesville, Georgia, United States
      • Teva Investigational Site 12486
    • Lawrenceville, Georgia, United States
      • Teva Investigational Site 12497
    • Savannah, Georgia, United States
      • Teva Investigational Site 12480
  • Illinois
    • Shiloh, Illinois, United States
      • Teva Investigational Site 12508
  • Iowa
    • Iowa City, Iowa, United States
      • Teva Investigational Site 12518
  • Louisiana
    • Covington, Louisiana, United States
      • Teva Investigational Site 12523
  • Missouri
    • Warrensburg, Missouri, United States
      • Teva Investigational Site 12495
  • New Jersey
    • Northfield, New Jersey, United States
      • Teva Investigational Site 12509
  • New York
    • Brooklyn, New York, United States
      • Teva Investigational Site 12524
  • North Carolina
    • Raleigh, North Carolina, United States
      • Teva Investigational Site 12473
  • Ohio
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 12477
    • Cleveland, Ohio, United States
      • Teva Investigational Site 12525
    • Middleburg Heights, Ohio, United States
      • Teva Investigational Site 12502
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 12478
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 12487
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 12506
    • Tulsa, Oklahoma, United States
      • Teva Investigational Site 12492
  • Oregon
    • Gresham, Oregon, United States
      • Teva Investigational Site 12507
  • Pennsylvania
    • Normal, Pennsylvania, United States
      • Teva Investigational Site 12501
    • Pittsburgh, Pennsylvania, United States
      • Teva Investigational Site 12493
    • Upland, Pennsylvania, United States
      • Teva Investigational Site 12488
  • South Carolina
    • Greenville, South Carolina, United States
      • Teva Investigational Site 12514
    • Orangeburg, South Carolina, United States
      • Teva Investigational Site 12474
    • Spartanburg, South Carolina, United States
      • Teva Investigational Site 12479
  • Texas
    • Boerne, Texas, United States
      • Teva Investigational Site 12489
    • Waco, Texas, United States
      • Teva Investigational Site 12475
  • Virginia
    • Burke, Virginia, United States
      • Teva Investigational Site 12491
    • Charlottesville, Virginia, United States
      • Teva Investigational Site 12504
    • Richmond, Virginia, United States
      • Teva Investigational Site 12482
    • Richmond, Virginia, United States
      • Teva Investigational Site 12498
  • Washington
    • Spokane, Washington, United States
      • Teva Investigational Site 12490

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo MDPI QID; Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks.	Drug: Placebo; Matching Placebo delivered via a multidose dry powder inhaler (MDPI).; Drug: ProAir HFA inhaler; Rescue medication, ProAir hydrofluoroalkane (HFA) inhaler, was dispensed at the run-in visit for the relief of asthma symptoms to be administered as needed.; Other Names: albuterol
Experimental: Albuterol MDPI 180 mcg QID; Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks.	Drug: ProAir HFA inhaler; Rescue medication, ProAir hydrofluoroalkane (HFA) inhaler, was dispensed at the run-in visit for the relief of asthma symptoms to be administered as needed.; Other Names: albuterol; Drug: Albuterol MDPI; 90 mcg/actuation of the multidose dry powder inhaler (MDPI).; Other Names: Spiromax®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Following measurement of the baseline FEV1 and dose administration on Days 1 and 22, FEV1 values (highest of 3 acceptable maneuvers) will be obtained at 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±10), 120 (±10), 240 (±10), and 360 (±10) minutes after the completion of dosing. Predicted FEV1 values were computed and adjusted for age, height, and gender according to Eigen et al (Eigen et al 2001) for participants 4 to 5 years of age and to Quanjer et al (Quanjer et al 1995) for participants aged 6 to 11 years using ATS criteria (American Thoracic Society/European Respiratory Society Statement 2007).	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Serial PEF measurements were obtained via spirometry. PEF measures for purpose of serial PEF assessment (pre and postdose) were collected from the spirometer assessed PEF, utilizing the values from the efforts selected based on the highest of 3 acceptable FEV1 maneuvers.	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
Summary of Participants With Adverse Events	Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator as mild (no limitation of usual activities), moderate, or severe (inability to carry out usual activities). Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.	6 Months

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: April 28, 2014
• First Submitted That Met QC Criteria: April 28, 2014
• First Posted (Estimate): April 30, 2014

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: ABS-AS-303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No