Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® Hydrofluoroalkane (HFA) in Pediatric Patients

NCT01899144 | Completed Phase 2 Results

• 1 other identifier: ABS-AS-202
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 22

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.

Conditions

Asthma

Keywords

Albuterol Spiromax; ProAir HFA; albuterol sulfate

Outcome Measures

Primary Outcomes (1)

• Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose

  Percent predicted FEV1: measured FEV1 as a percent of the "predicted values" for the patients of similar characteristics. Predicted FEV1 values were computed and adjusted for age, height, and gender for patients aged 4-5 years (Eigen et al 2001) and for patients aged 6-11 years (Quanjer et al 1995) using ATS/European Thoracic Society (ERS) criteria applicable to pediatric patients (ATS/ERS 2007). The percent predicted FEV1 (PPFEV1) area under the curve (AUC)0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose PPFEV1 values from each post-dose PPFEV1 determination.

  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 (2)

• Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6)

  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

• Participants With Treatment-Emergent Adverse Events

  Day 1 up to Day 35

Study Arms (5)

Albuterol Spiromax 90 mcg

EXPERIMENTAL

At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, one of the DPIs contains Albuterol Spiromax 90 mcg; the other three devices contained placebo.

Drug: Albuterol Spiromax; Drug: Placebo

Albuterol Spiromax 180 mcg

EXPERIMENTAL

At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, both of the DPIs contain Albuterol Spiromax 90 mcg for a total dose of 180 mcg; the MDIs contained placebo.

Drug: Albuterol Spiromax; Drug: Placebo

ProAir HFA 90 mcg

ACTIVE COMPARATOR

At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, one of the MDIs contains ProAir HFA 90 mcg; the other three devices contained placebo.

Drug: ProAir HFA; Drug: Placebo

ProAir HFA 180 mcg

ACTIVE COMPARATOR

At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, both of the MDIs contain ProAir HFA 90 mcg for a total dose of 180 mcg; the DPIs contained placebo.

Drug: ProAir HFA; Drug: Placebo

Placebo

PLACEBO COMPARATOR

At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, all devices contain placebo.

Drug: Placebo

Interventions

Albuterol Spiromax DRUG

Albuterol Spiromax® Inhalation Aerosol contains 90 mcg albuterol per actuation orally inhaled in a single dose dry powder inhaler (DPI). Participants took doses at either the 90 or 180 mcg levels. If the higher level, two DPIs filled with Albuterol Spiromax® were used.

Also known as: Spiromax®, albuterol

Albuterol Spiromax 180 mcg; Albuterol Spiromax 90 mcg

ProAir HFA DRUG

ProAir® HFA Inhalation Aerosol contains 90 mcg albuterol per actuation orally inhaled in a single dose metered dose inhaler (MDI). Participants took doses at either the 90 or 180 mcg levels. If the higher level, two MDIs filled with ProAir HFA were used.

Also known as: ProAir®

ProAir HFA 180 mcg; ProAir HFA 90 mcg

Placebo DRUG

Single dose MDIs and DPIs containing placebo taken as a single orally-inhaled actuation each.

Albuterol Spiromax 180 mcg; Albuterol Spiromax 90 mcg; Placebo; ProAir HFA 180 mcg; ProAir HFA 90 mcg

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 pre-menarchal female 4-11 years of age, inclusive, as of the screening visit
• 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)
• Has the ability to self-perform spirometry reproducibly per American Thoracic Society (ATS) guidelines
• 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.
• 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
• 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
• Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter
• Has the ability to demonstrate acceptable and reproducible inhalation technique with the Spiromax and metered dose inhaler (MDI) devices

You may not qualify if:

• Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (lactose, ethanol, etc.)
• 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
• 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, etc.) that has not resolved within 4 weeks preceding the screening visit
• 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.
• 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 period prescribed per protocol prior to the screening visit.
• Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol
• The dosage of any required intranasal corticosteroid and/or cromone has not been stable for at least 2 weeks prior to the screening visit.
• Treated with oral or injectable corticosteroids within the 6 weeks before the screening visit.

Sponsors & Collaborators

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

Study Sites (22)

Teva Investigational Site 10598

Birmingham, Alabama, United States

Location

Teva Investigational Site 10593

Little Rock, Alaska, United States

Location

Teva Investigational Site 10610

Costa Mesa, California, United States

Location

Teva Investigational Site 10582

Huntington Beach, California, United States

Location

Teva Investigational Site 10606

Orange, California, United States

Location

Teva Investigational Site 10597

San Jose, California, United States

Location

Teva Investigational Site 10596

Jacksonville, Florida, United States

Location

Teva Investigational Site 10599

Lawrenceville, Georgia, United States

Location

Teva Investigational Site 10580

Savannah, Georgia, United States

Location

Teva Investigational Site 10592

Normal, Illinois, United States

Location

Teva Investigational Site 10602

Missoula, Montana, United States

Location

Teva Investigational Site 10578

Raleigh, North Carolina, United States

Location

Teva Investigational Site 10577

Oklahoma City, Oklahoma, United States

Location

Teva Investigational Site 10589

Medford, Oregon, United States

Location

Teva Investigational Site 10604

Portland, Oregon, United States

Location

Teva Investigational Site 10591

Charleston, South Carolina, United States

Location

Teva Investigational Site 10609

Orangeburg, South Carolina, United States

Location

Teva Investigational Site 10579

Spartanburg, South Carolina, United States

Location

Teva Investigational Site 10588

Boerne, Texas, United States

Location

Teva Investigational Site 10605

New Braunfels, Texas, United States

Location

Teva Investigational Site 10583

San Antonio, Texas, United States

Location

Teva Investigational Site 10576

Waco, Texas, United States

Location

Related Publications (2)

• 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.

  PMID: 27657520 DERIVED

• 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; Procaterol

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; Hydroxyquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

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

ustevatrials@tevapharm.com

215-591-3000

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 15, 2013
• Study Start: July 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: January 26, 2022
• Results First Posted: February 8, 2016

Record last verified: 2022-01

Locations

US (22)