Phase4/Symbicort® Versus Pulmicort Flexhaler® in African Americans

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00702325

Acronym

Titan

Enrollment

311

Registered

2008-06-20

Start date

2008-06-30

Completion date

2009-09-30

Last updated

2012-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma

Brief summary

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.

Interventions

DRUGBudesonide / formoterol fumarate (SYMBICORT)

160/4.5 μg x 2 actuations twice daily (bid)

DRUGBudesonide

inhalation powder 180 μg x 2 inhalations bid (PULMICORT)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change From Baseline in Evening Peak Expiratory Flow (PM PEF) Averaged Over the Treatment Period	Baseline to 12 weeks	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) Averaged Over the Treatment Period	Baseline to 12 weeks	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Change From Baseline in Pre-dose Forced Expiratory Flow (FEF 25-75%) Averaged Over the Treatment Period	Baseline to 12 weeks	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.
Number of First Predefined Asthma Events by Inhaled Corticosteroid (ICS) Dose at Entry	12 weeks	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)
Number of Withdrawals Due to a Predefined Asthma Event	12 weeks	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)
Change From Baseline in Total Average Daily Asthma Symptom Score Averaged Over the Treatment Period	Baseline to 12 weeks	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
Change From Baseline in Nighttime Asthma Symptom Score Averaged Over the Treatment Period	Baseline to 12 weeks	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)
Change From Baseline in Daytime Asthma Symptom Score Averaged Over the Treatment Period	Baseline to 12 weeks	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)
Change From Baseline in Awakening-free Nights Averaged Over the Treatment Period	Baseline to 12 weeks	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
Change From Baseline to the Average in Total Rescue Medication Use Averaged Over the Treatment Period	Baseline to 12 weeks	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
Change From Baseline to the Average in Nighttime Rescue Medication Use Averaged Over the Treatment Period	Baseline to 12 weeks	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
Change From Baseline in Morning Peak Expiratory Flow (AM PEF) Averaged Over the Treatment Period	Baseline to 12 weeks	Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period
Change From Baseline to the Average in Rescue Medication-free Days Averaged Over the Treatment Period	Baseline to 12 weeks	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
Change From Baseline in Asthma Symptom-free Days Averaged Over the Treatment Period	Baseline to 12 weeks	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
Change From Baseline to the Average for Asthma-control Days Averaged Over the Treatment Period	Baseline to 12 weeks	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
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)	12 week	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
Change From Baseline to End of Treatment in Overall Score on the Asthma Quality of Life Questionnaire-Standardized (AQLQ[S])	Baseline to 12 weeks	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
Proportion of Participants Who Reported on the Asthma Control Test (ACT) That Their Asthma Was Controlled at the Last Week of Treatment	12 weeks	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.
Change From Baseline to Last Week of Treatment in Scores on the Asthma Impact Survey (AIS)	Baseline to 12 weeks	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.
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)	12 week	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.
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)	1 week	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
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)	1 week	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.
Change From Baseline to the Average in Daytime Medication Use Averaged Over the Treatment Period	Baseline to 12 weeks	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

Countries

United States

Participant flow

Recruitment details

First participant enrolled on 05 June 2008, last participant last visit on 10 September 2009.

Pre-assignment details

10 subjects were excluded from the FAS: 9 who received the incorrect study medication and 1 who was randomized to receive SYMBICORT pMDI, but never received study medication. Therefore, 153 subjects (from 156 randomized to Symbicort) and 148 (from 155 randomized to Budesonide) were included in the FAS used to present baseline characteristics.

Participants by arm

Arm	Count
Symbicort Symbicort pressurized metered dose inhaler (pMDI) 160/4.5 mcg x 2 actuations, twice daily.	153
Budesonide Budesonide inhalation dry powder inhaler (DPI) 180 mcg x 2 inhalations, twice daily.	148
Total	301

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Developed study discontinuation criteria	18	28
Overall Study	Didn't follow study medication dosage	0	2
Overall Study	Incorrect enrollment	5	7
Overall Study	Incorrectly Discontinued	0	1
Overall Study	Lost to Follow-up	3	4
Overall Study	Severe noncompliance to protocol	3	3
Overall Study	Termination due to lab results	1	0
Overall Study	Withdrawal by Subject	7	7
Overall Study	Withdrew consent	0	1

Baseline characteristics

Characteristic	Symbicort	Budesonide	Total
Age Continuous	38.6 Years STANDARD_DEVIATION 13.8	39.8 Years STANDARD_DEVIATION 15.4	39.2 Years STANDARD_DEVIATION 14.6
Sex: Female, Male Female	109 Participants	87 Participants	196 Participants
Sex: Female, Male Male	44 Participants	61 Participants	105 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	18 / 156	12 / 155
serious Total, serious adverse events	1 / 156	2 / 155

Outcome results

Primary

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