Phase4/Symbicort® Versus Pulmicort Flexhaler® in African Americans (Titan)

A 12-wk, Rand., Double-blind, Double Dummy, Multi-ctr., Phase IV Study Comparing Efficacy and Safety of SYMBICORT® pMDI 160/4.5 ug x 2 Actuations Twice Daily Versus Pulmicort® (Budesonide Inhalation Powder DPI) 180 ug x 2 Inhalations Twice Daily, in Adult and Adolescent African American Subjects With Asthma

To compare the efficacy of SYMBICORT® pMDI 160/4.5 μg x 2 actuations twice daily (bid) to that of budesonide inhalation powder DPI 180 μg x 2 inhalations bid, in African American(self-reported) subjects with inhaled corticosteroid (ICS) dependent asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Budesonide / formoterol fumarate (SYMBICORT); Drug: Budesonide

• Study Type: Interventional
• Enrollment (Actual): 311
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Pell City, Alabama, United States
      • Research Site
  • Arkansas
    • Bentonville, Arkansas, United States
      • Research Site
    • Hot Springs, Arkansas, United States
      • Research Site
    • Little Rock, Arkansas, United States
      • Research Site
    • Malvern, Arkansas, United States
      • Research Site
  • California
    • Huntington Park, California, United States
      • Research Site
    • Long Beach, California, United States
      • Research Site
    • Los Angeles, California, United States
      • Research Site
    • Los Angles, California, United States
      • Research Site
    • Orange, California, United States
      • Research Site
    • Rolling Hills Estates, California, United States
      • Research Site
  • Colorado
    • Centennial, Colorado, United States
      • Research Site
    • Colorado Springs, Colorado, United States
      • Research Site
  • Connecticut
    • Waterbury, Connecticut, United States
      • Research Site
  • Florida
    • Inverness, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • Ocala, Florida, United States
      • Research Site
    • Tallahassee, Florida, United States
      • Research Site
    • Tampa, Florida, United States
      • Research Site
  • Georgia
    • Alpharetta, Georgia, United States
      • Research Site
    • Atlanta, Georgia, United States
      • Research Site
    • Decatur, Georgia, United States
      • Research Site
    • Lawrenceville, Georgia, United States
      • Research Site
    • Lithia Springs, Georgia, United States
      • Research Site
    • Lovejoy, Georgia, United States
      • Research Site
  • Illinois
    • Chicago, Illinois, United States
      • Research Site
  • Maryland
    • Hagerstown, Maryland, United States
      • Research Site
    • Lanham, Maryland, United States
      • Research Site
    • Largo, Maryland, United States
      • Research Site
    • Towson, Maryland, United States
      • Research Site
  • Michigan
    • Flint, Michigan, United States
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States
      • Research Site
    • St. Louis, Missouri, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New Jersey
    • Skillman, New Jersey, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
    • North Syracuse, New York, United States
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States
      • Research Site
    • Greenville, North Carolina, United States
      • Research Site
    • Raleigh, North Carolina, United States
      • Research Site
  • Oregon
    • Portland, Oregon, United States
      • Research Site
  • Pennsylvania
    • Blue Bell, Pennsylvania, United States
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Research Site
    • Spartanburg, South Carolina, United States
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States
      • Research Site
  • Texas
    • Arlington, Texas, United States
      • Research Site
    • Dallas, Texas, United States
      • Research Site
    • Fort Worth, Texas, United States
      • Research Site
    • Ft. Worth, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
    • McKinney, Texas, United States
      • Research Site
    • Plano, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site
    • Waco, Texas, United States
      • Research Site
  • Virginia
    • Emporia, Virginia, United States
      • Research Site
    • Richmond, Virginia, United States
      • Research Site
    • Virginia Beach, Virginia, United States
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Research Site

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:

• African American (self-reported)
• Documented clinical diagnosis of asthma as defined by the American Thoracic Society (ATS) for at least 6 months prior to Visit 2 and be in stable condition.
• FEV1, measured ≥6 hours after the last dose of short-acting β2-agonist and at least 48 hours after LABA, of 45%-85%, inclusive, of predicted normal.

Exclusion Criteria:

• Has been hospitalized at least once for an asthma related condition during the 6 months prior to Visit 2, or has required emergency treatment due to an asthma related condition more than once in the 3 months prior to Visit 2.
• Has required treatment with systemic corticosteroids (eg, oral, parenteral, ocular, or rectal) for any reason within the 30 days prior to Visit 2.
• Has a respiratory infection or other viral/bacterial illness, or is recovering from such an illness at the time of Visit 3 that, in the Investigator's opinion, will interfere with the subject's lung function and/or ability to perform spirometry

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
Experimental: 1	Drug: Budesonide / formoterol fumarate (SYMBICORT); 160/4.5 μg x 2 actuations twice daily (bid); Other Names: SYMBICORT
Active Comparator: 2	Drug: Budesonide; inhalation powder 180 μg x 2 inhalations bid (PULMICORT); Other Names: PULMICORT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) Averaged Over Treatment Period	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning Peak Expiratory Flow (AM PEF) Averaged Over the Treatment Period	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline in Evening Peak Expiratory Flow (PM PEF) Averaged Over the Treatment Period	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) Averaged Over the Treatment Period	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline in Pre-dose Forced Expiratory Flow (FEF 25-75%) Averaged Over the Treatment Period	Mean change of the FEF (25-75%) value at the baseline (Visit 3) compared to average value of the FEF (25-75%) recorded at visits during treatment period (to week 12). The mean change was calculated.	Baseline to 12 weeks
Number of First Predefined Asthma Events by Inhaled Corticosteroid (ICS) Dose at Entry	Total number of participants with any first predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma medication)	12 weeks
Number of Withdrawals Due to a Predefined Asthma Event	Total number of participants who withdrew due to a predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma meds)	12 weeks
Change From Baseline in Total Average Daily Asthma Symptom Score Averaged Over the Treatment Period	Diary assessment of total asthma symptoms score (treatment average) by Inhaled Corticosteroid (ICS) dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline in Nighttime Asthma Symptom Score Averaged Over the Treatment Period	Diary assessment of nighttime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS)	Baseline to 12 weeks
Change From Baseline in Daytime Asthma Symptom Score Averaged Over the Treatment Period	Diary assessment of daytime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS)	Baseline to 12 weeks
Change From Baseline in Awakening-free Nights Averaged Over the Treatment Period	Diary assessment of number of nights free from awakenings due to asthma; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline to the Average in Total Rescue Medication Use Averaged Over the Treatment Period	Diary assessment of total daily puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline to the Average in Nighttime Rescue Medication Use Averaged Over the Treatment Period	Diary assessment of total nighttime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline to the Average in Daytime Medication Use Averaged Over the Treatment Period	Diary assessment of total daytime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline to the Average in Rescue Medication-free Days Averaged Over the Treatment Period	Diary assessment of total (percent) days free from rescue medication use for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline in Asthma Symptom-free Days Averaged Over the Treatment Period	Diary assessment of number (percent) of days free from asthma symptoms by ICS dose at entry; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Change From Baseline to the Average for Asthma-control Days Averaged Over the Treatment Period	Diary assessment of number (percent) of asthma-control days (defined as days that were free of symptoms and nighttime and daytime rescue medication use); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Perception of Onset of Medication Effect at Last Week of Treatment Assessed by Number of Participants Who Agreed With Item 2 on the Onset of Effect Questionnaire (OEQ)	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at last week of treatment - During the past week, you could feel your medication begin to work right away	12 week
Change From Baseline to End of Treatment in Overall Score on the Asthma Quality of Life Questionnaire-Standardized (AQLQ[S])	Mean change in overall score at end of treatment for participants age 17 years and older (scores ranged from 1 to 7, with higher scores indicating better quality of life); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period	Baseline to 12 weeks
Proportion of Participants Who Reported on the Asthma Control Test (ACT) That Their Asthma Was Controlled at the Last Week of Treatment	There are 5 questions in the survey, and each question has 5 responses (total score for each question can range from 1 to 5). To score the survey, responses to the 5 questions are added to yield a total score that ranges from 5 (poor control of asthma control) to 25 (complete control of asthma). Score of 20 or higher was indicative of well-controlled asthma.	12 weeks
Change From Baseline to Last Week of Treatment in Scores on the Asthma Impact Survey (AIS)	There are 6 questions in the survey, and each question has 5 responses (total score for each question can range from 6 to 13). Responses to the 6 questions were added to yield a total score that ranged from 36 to 78. Scoring is based on a norm-based method. Higher AIS scores indicated more asthma impact and poorer quality of life; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period.	Baseline to 12 weeks
Perception of Onset of Medication Effect at Last Week of Treatment Assessed by Number of Participants Who Agreed With Item 5 on the Onset of Effect Questionnaire (OEQ)	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at last week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work.	12 week
Perception of Onset of Medication Effect at First Week of Treatment Assessed by Number of Participants Who Agreed With Item 2 on the Onset of Effect Questionnaire (OEQ)	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at first week of treatment - During the past week, you could feel your medication begin to work right away	1 week
Perception of Onset of Medication Effect at First Week of Treatment Assessed by Number of Participants Who Agreed With Item 5 on the Onset of Effect Questionnaire (OEQ)	Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at first week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work.	1 week

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Ubaldo Martin, MD, AstraZeneca; Study Director: Tomas LG Andersson, AstraZeneca

Publications and helpful links

General Publications

• Murphy KR, Uryniak T, Martin UJ, Zangrilli J. The effect of budesonide/formoterol pressurized metered-dose inhaler on predefined criteria for worsening asthma in four different patient populations with asthma. Drugs R D. 2012 Mar 1;12(1):9-14. doi: 10.2165/11630600-000000000-00000. Erratum In: Drugs R D. 2012 Mar 1;12(1):15.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: June 19, 2008
• First Submitted That Met QC Criteria: June 19, 2008
• First Posted (Estimate): June 20, 2008

Study Record Updates

• Last Update Posted (Estimate): November 9, 2012
• Last Update Submitted That Met QC Criteria: October 10, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Asthma
• 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; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: D589BL00003