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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT01424813
First received: August 25, 2011
Last updated: May 28, 2015
Last verified: May 2015
  Purpose

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


Condition Intervention Phase
Asthma
Drug: Placebo MDPI
Drug: Albuterol MDPI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-week Comparison of the Efficacy and Safety of Albuterol Spiromax® Versus Placebo in Subjects 12 Years and Older With Persistent Asthma

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period [ Time Frame: Day 1, Day 8 and Day 85 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

    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.


  • Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]

    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.


  • Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]

    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.


  • Participants With Adverse Events [ Time Frame: Day 1 to Day 92 ] [ Designated as safety issue: Yes ]
    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.

  • Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group [ Time Frame: Day 1 (Baseline), Day 85 ] [ Designated as safety issue: Yes ]
    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

  • Participants With Clinically Significant Vital Sign Assessments [ Time Frame: Day 8, Day 85 ] [ Designated as safety issue: Yes ]

    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



Other Outcome Measures:
  • Percent Change From Baseline in FEV1 AUC 0-6 Over the 12-week Treatment Period [ Time Frame: Day 1, Day 8, Day 85 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in FEV1 AUC 0-6 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in FEV1 AUC [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in FEV1 AUC [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
  • Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose Over the 12-week Treatment Period [ Time Frame: Day 1, Day 8, Day 85 ] [ Designated as safety issue: No ]
  • Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 85 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
  • Time to Onset of Effect (Change in FEV1 of 12% From Baseline Within 30 Minutes Postdose) [ Time Frame: Day 1, Day 8, Day 85 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Day 1, Day 8, Day 85 ] [ Designated as safety issue: No ]
  • Time to Onset of Effect (Change in FEV1 of 15% From Baseline Within 30 Minutes Postdose)for Those Who Responded in 30 Minutes [ Time Frame: Day 1, Day 8, Day 85 ] [ Designated as safety issue: No ]
  • Duration of Response on Days 1, 8 and 85 [ Time Frame: Day 1, Day 8, Day 85 ] [ Designated as safety issue: No ]
    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

  • Percent of Symptom Free Days on the Patient Diary [ Time Frame: Treatment days 1 through 85 ] [ Designated as safety issue: No ]
  • Percent of Rescue Medication Free Days in the Patient Diary [ Time Frame: Treatment days 1 through 85 ] [ Designated as safety issue: No ]
  • Morning Peak Expiratory Flow Reading Reported on Patient Diary [ Time Frame: Treatment days 1 through 85 ] [ Designated as safety issue: No ]

Enrollment: 158
Study Start Date: December 2012
Study Completion Date: November 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: ProAir® RespiClick, Albuterol Spiromax®

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424813

  Show 38 Study Locations
Sponsors and Collaborators
Teva Branded Pharmaceutical Products, R&D Inc.
Investigators
Study Director: Clinical Project Leader Teva Respiratory R&D
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01424813     History of Changes
Other Study ID Numbers: ABS-AS-301
Study First Received: August 25, 2011
Results First Received: May 1, 2015
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Asthma
dry powder inhaler
short-acting beta2-agonist
SABA
bronchoconstriction
bronchodilation
bronchodilator
metered dose inhaler

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Albuterol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents

ClinicalTrials.gov processed this record on July 30, 2015