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

NCT02126839 | Completed Phase 3 Results

• 1 other identifier: ABS-AS-303
• Study Type: interventional
• Target: 186
• Locations: 2 countries
• Sites: 52

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

  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

  6 Months

Study Arms (2)

Placebo MDPI QID

PLACEBO COMPARATOR

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; Drug: ProAir HFA inhaler

Albuterol MDPI 180 mcg QID

EXPERIMENTAL

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: Albuterol MDPI; Drug: ProAir HFA inhaler

Interventions

Albuterol MDPI DRUG

90 mcg/actuation of the multidose dry powder inhaler (MDPI).

Also known as: Spiromax®

Albuterol MDPI 180 mcg QID

Placebo DRUG

Matching Placebo delivered via a multidose dry powder inhaler (MDPI).

Placebo MDPI QID

ProAir HFA inhaler DRUG

Rescue medication, ProAir hydrofluoroalkane (HFA) inhaler, was dispensed at the run-in visit for the relief of asthma symptoms to be administered as needed.

Also known as: albuterol

Albuterol MDPI 180 mcg QID; Placebo MDPI QID

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study related procedure
• Male or premenarchal female 4-11 years of age, inclusive, as of the screening visit (SV)
• 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
• Has the ability to perform spirometry reproducibly consistent with ATS guidelines and protocol-specific guidelines
• 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%.)
• 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%.)
• 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
• Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter
• Can tolerate the withdrawal of applicable medications for qualification at screening
• 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
• 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)
• The patient is able to correctly use the MDPI device, either alone or with assistance by a parent/guardian.

You may not qualify if:

• Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (eg, lactose, ethanol)
• 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
• History of severe milk protein allergy
• 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
• 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.
• 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
• Use of any prohibited concomitant medications within the washout prescribed per protocol prior to study visits
• Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol as described in the protocol
• 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.
• 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
• Any other medical or psychological condition that in the investigator's opinion should preclude study enrollment
• Previous participation (received MDPI study medication) in an Albuterol MDPI study
• Study participation by clinical investigator site employees and/or their immediate relatives
• 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.
• Require continuous treatment with β-blockers, MAO inhibitors, tricyclic antidepressants, anticholinergics, and/or systemic corticosteroids

Sponsors & Collaborators

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

Study Sites (52)

Teva Investigational Site 12496

Birmingham, Alabama, United States

Location

Teva Investigational Site 12500

Mobile, Alabama, United States

Location

Teva Investigational Site 12481

Little Rock, Alaska, United States

Location

Teva Investigational Site 12515

Anaheim, California, United States

Location

Teva Investigational Site 12505

Costa Mesa, California, United States

Location

Teva Investigational Site 12476

Huntington Beach, California, United States

Location

Teva Investigational Site 12519

Los Angeles, California, United States

Location

Teva Investigational Site 12484

Mission Viejo, California, United States

Location

Teva Investigational Site 12510

Riverside, California, United States

Location

Teva Investigational Site 12483

Rolling Hills Estates, California, United States

Location

Teva Investigational Site 12511

Sacramento, California, United States

Location

Teva Investigational Site 12485

Stockton, California, United States

Location

Teva Investigational Site 12512

Centennial, Colorado, United States

Location

Teva Investigational Site 12522

Gainesville, Florida, United States

Location

Teva Investigational Site 12535

Hollywood, Florida, United States

Location

Teva Investigational Site 12526

Miami, Florida, United States

Location

Teva Investigational Site 12516

Orlando, Florida, United States

Location

Teva Investigational Site 12517

Tamarac, Florida, United States

Location

Teva Investigational Site 12527

Vero Beach, Florida, United States

Location

Teva Investigational Site 12513

Winter Park, Florida, United States

Location

Teva Investigational Site 12486

Gainesville, Georgia, United States

Location

Teva Investigational Site 12497

Lawrenceville, Georgia, United States

Location

Teva Investigational Site 12480

Savannah, Georgia, United States

Location

Teva Investigational Site 12508

Shiloh, Illinois, United States

Location

Teva Investigational Site 12518

Iowa City, Iowa, United States

Location

Teva Investigational Site 12523

Covington, Louisiana, United States

Location

Teva Investigational Site 12495

Warrensburg, Missouri, United States

Location

Teva Investigational Site 12509

Northfield, New Jersey, United States

Location

Teva Investigational Site 12524

Brooklyn, New York, United States

Location

Teva Investigational Site 12473

Raleigh, North Carolina, United States

Location

Teva Investigational Site 12477

Cincinnati, Ohio, United States

Location

Teva Investigational Site 12525

Cleveland, Ohio, United States

Location

Teva Investigational Site 12502

Middleburg Heights, Ohio, United States

Location

Teva Investigational Site 12478

Oklahoma City, Oklahoma, United States

Location

Teva Investigational Site 12487

Oklahoma City, Oklahoma, United States

Location

Teva Investigational Site 12506

Oklahoma City, Oklahoma, United States

Location

Teva Investigational Site 12492

Tulsa, Oklahoma, United States

Location

Teva Investigational Site 12507

Gresham, Oregon, United States

Location

Teva Investigational Site 12501

Normal Square, Pennsylvania, United States

Location

Teva Investigational Site 12493

Pittsburgh, Pennsylvania, United States

Location

Teva Investigational Site 12488

Upland, Pennsylvania, United States

Location

Teva Investigational Site 12514

Greenville, South Carolina, United States

Location

Teva Investigational Site 12474

Orangeburg, South Carolina, United States

Location

Teva Investigational Site 12479

Spartanburg, South Carolina, United States

Location

Teva Investigational Site 12489

Boerne, Texas, United States

Location

Teva Investigational Site 12475

Waco, Texas, United States

Location

Teva Investigational Site 12491

Burke, Virginia, United States

Location

Teva Investigational Site 12504

Charlottesville, Virginia, United States

Location

Teva Investigational Site 12482

Richmond, Virginia, United States

Location

Teva Investigational Site 12498

Richmond, Virginia, United States

Location

Teva Investigational Site 12490

Spokane, Washington, United States

Location

Teva Investigational Site 12533

Papillion, NE, Thailand

Location

Related Publications (1)

• 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.

  PMID: 27523719 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Sponsor's Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2014
• First Posted: April 30, 2014
• Study Start: May 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: November 9, 2021
• Results First Posted: February 5, 2016

Record last verified: 2021-11

Locations

US (51); TH (1)