A 12-week Study to Compare the Efficacy and Safety of Albuterol Spiromax® Versus a Placebo in People 12 Years and Older With Persistent Asthma

A 12-week Comparison of the Efficacy and Safety of Albuterol Spiromax® Versus Placebo in Subjects 12 Years and Older With Persistent Asthma

The study will measure the change in lung function in subjects with asthma after inhaling from either of two inhalers: Albuterol Spiromax® or placebo.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Teva Investigational Site 10077
  • Arizona
    • Phoenix, Arizona, United States
      • Teva Investigational Site 10079
  • California
    • Costa Mesa, California, United States
      • Teva Investigational Site 10569
    • Fountain Valley, California, United States
      • Teva Investigational Site 10053
    • Huntington Beach, California, United States
      • Teva Investigational Site 10065
    • Huntington Beach, California, United States
      • Teva Investigational Site 10572
    • Los Angeles, California, United States
      • Teva Investigational Site 10075
    • Roseville, California, United States
      • Teva Investigational Site 10061
    • San Diego, California, United States
      • Teva Investigational Site 10066
  • Colorado
    • Denver, Colorado, United States
      • Teva Investigational Site 10068
    • Denver, Colorado, United States
      • Teva Investigational Site 10069
  • Florida
    • Miami, Florida, United States
      • Teva Investigational Site 10058
    • Miami, Florida, United States
      • Teva Investigational Site 10060
    • Ormond Beach, Florida, United States
      • Teva Investigational Site 10064
  • Georgia
    • Savannah, Georgia, United States
      • Teva Investigational Site 10071
  • Kansas
    • Wichita, Kansas, United States
      • Teva Investigational Site 10073
  • Kentucky
    • Owensboro, Kentucky, United States
      • Teva Investigational Site 10070
  • Maryland
    • Bethesda, Maryland, United States
      • Teva Investigational Site 10063
    • Gaithersburg, Maryland, United States
      • Teva Investigational Site 10571
    • Wheaton, Maryland, United States
      • Teva Investigational Site 10067
  • Missouri
    • St. Louis, Missouri, United States
      • Teva Investigational Site 10072
  • Montana
    • Missoula, Montana, United States
      • Teva Investigational Site 10050
  • North Carolina
    • Raleigh, North Carolina, United States
      • Teva Investigational Site 10057
  • Ohio
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 10051
    • Sylvania, Ohio, United States
      • Teva Investigational Site 10078
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 10054
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 10568
    • Tulsa, Oklahoma, United States
      • Teva Investigational Site 10055
  • Oregon
    • Medford, Oregon, United States
      • Teva Investigational Site 10056
    • Medford, Oregon, United States
      • Teva Investigational Site 10076
  • South Carolina
    • Charleston, South Carolina, United States
      • Teva Investigational Site 10684
    • Spartanburg, South Carolina, United States
      • Teva Investigational Site 10570
  • Texas
    • Live Oak, Texas, United States
      • Teva Investigational Site 10049
    • San Antonio, Texas, United States
      • Teva Investigational Site 10052
    • Waco, Texas, United States
      • Teva Investigational Site 10685
  • Virginia
    • Fairfax, Virginia, United States
      • Teva Investigational Site 10059
  • Washington
    • Puyallup, Washington, United States
      • Teva Investigational Site 10074
    • Tacoma, Washington, United States
      • Teva Investigational Site 10062

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent/assent
• General good health
• Persistent asthma, with an FEV1 50-80% predicted.
• Ability to perform spirometry in an acceptable manner as per protocol guidelines.
• Ability to perform PEFR with a handheld peak flow meter.
• Demonstration of reversible bronchoconstriction as verified by a 15% or greater increase from baseline FEV1.
• Taking inhaled corticosteroids at a stable dose for at least 4 weeks prior to the Screening Visit.
• Non-smokers.
• Capable of understanding the requirements, risks, and benefits of study participation.
• Other inclusion criteria apply.

Exclusion Criteria:

• Participation in any investigational drug trial within the 30 days preceding the Screening Visit (SV).
• A known hypersensitivity to albuterol or any of the excipients in the formulations.
• History of severe milk protein allergy.
• History of a respiratory infection or disorder that has not resolved within the 2 weeks preceding the Screening Visit (SV).
• Currently requires treatment with β2-adrenergic receptor antagonists or non-selective β-receptor blocking agents.
• History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation.
• Any asthma exacerbation requiring oral corticosteroids within 3 months of the Screening Visit (SV). A subject must not have had any hospitalization for asthma within 6 months prior to the Screening Visit (SV).
• Historical or current evidence of any clinically significant non-asthmatic acute or chronic condition including.
• Other exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo MDPI; Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Drug: Placebo MDPI; Placebo MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.; Other Names: Placebo Spiromax®
Experimental: Albuterol MDPI; Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.	Drug: Albuterol MDPI; Albuterol MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.; Other Names: ProAir® RespiClick, Albuterol Spiromax®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) of FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 1, Day 8 and Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 1. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 1
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 8. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 8
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 85. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 85
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 on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily 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.	Day 1 to Day 92
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group	Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint HEENT = head, eyes, ears, nose, throat	Day 1 (Baseline), Day 85
Participants With Clinically Significant Vital Sign Assessments	For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min). Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: > 160 beats/minute Diastolic blood pressure: >100 beats/minute Heart rate: >120 beats/minute	Day 8, Day 85

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in FEV1 AUC 0-6 Over the 12-week Treatment Period		Day 1, Day 8, Day 85
Percent Change From Baseline in FEV1 AUC 0-6		Day 1
Percent Change From Baseline in FEV1 AUC		Day 8
Percent Change From Baseline in FEV1 AUC		Day 85
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose Over the 12-week Treatment Period		Day 1, Day 8, Day 85
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 1		Day 1
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 8		Day 8
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 85		Day 85
Time to Onset of Effect (Change in FEV1 of 12% From Baseline Within 30 Minutes Postdose)		Day 1, Day 8, Day 85
Duration of Response Measured From the Time Post-dosing to the First Time After the Response Onset (Increase ≥12% Above Baseline) When the FEV1 Decreases to Less Than 12% Above Baseline (Within 6 Hours After Dosing) for Those Who Responded in 30 Minutes		Day 1, Day 8, Day 85
Time to Onset of Effect (Change in FEV1 of 15% From Baseline Within 30 Minutes Postdose)for Those Who Responded in 30 Minutes		Day 1, Day 8, Day 85
Duration of Response on Days 1, 8 and 85	Duration of response measured from the time post-dosing to the first time after the response onset (increase ≥15% above baseline) when the FEV1 decreases to less than 15% above baseline (within 6 hours after dosing) for those who responded within 30 minutes	Day 1, Day 8, Day 85
Percent of Symptom Free Days on the Patient Diary		Treatment days 1 through 85
Percent of Rescue Medication Free Days in the Patient Diary		Treatment days 1 through 85
Morning Peak Expiratory Flow Reading Reported on Patient Diary		Treatment days 1 through 85

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Raphael G, Taveras H, Iverson H, O'Brien C, Miller D. Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma. J Asthma. 2016;53(2):187-93. doi: 10.3109/02770903.2015.1070862. Epub 2015 Sep 15.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimate): August 29, 2011

Study Record Updates

• Last Update Posted (Estimate): June 26, 2015
• Last Update Submitted That Met QC Criteria: May 28, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Asthma; dry powder inhaler; short-acting beta2-agonist; SABA; bronchoconstriction; bronchodilation; bronchodilator; metered dose inhaler
• 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-301