Trial Outcomes & Findings for A Comparison of SYMBICORT® pMDI With Budesonide HFA pMDI in African American Subjects With Asthma. (NCT NCT00419952)

NCT ID: NCT00419952

Last Updated: 2012-10-30

Results Overview

An exacerbation was defined as symptomatic worsening requiring oral/systemic glucocorticoid therapy and/or emergency room visit and/or urgent care center visit and/or hospitalization.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

742 participants

Primary outcome timeframe

52 Weeks

Results posted on

2012-10-30

Participant Flow

First patient enrolled on 8 February 2007, the last patient completed the study on 30 November 2009. The study randomized participants only in the United States.

The study included a run-in period of 2 weeks when all patients were prescribed budesonide HFA pMDI 160 μg times 2 actuations BID at individual daily doses and rescue medication, as needed. To be randomized to treatment the patients needed to show pre-dose FEV1 of ≥50%. One patient in the budesonide group did not receive any dose.

Participant milestones

Participant milestones
Measure
Symbicort
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Overall Study
STARTED
377
365
Overall Study
COMPLETED
228
240
Overall Study
NOT COMPLETED
149
125

Reasons for withdrawal

Reasons for withdrawal
Measure
Symbicort
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Overall Study
Adverse Event
8
10
Overall Study
Withdrawal by Subject
44
43
Overall Study
Lost to Follow-up
43
34
Overall Study
Protocol Violation
32
24
Overall Study
Pregnancy
4
2
Overall Study
Physician Decision
1
3
Overall Study
Incorrectly enrolled
10
3
Overall Study
Intake of prohibited medication
2
2
Overall Study
Occurence of 2 or more exacerbations
2
0
Overall Study
Diary or medication non-compliance
2
4
Overall Study
Abnormal ECG
1
0

Baseline Characteristics

A Comparison of SYMBICORT® pMDI With Budesonide HFA pMDI in African American Subjects With Asthma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Symbicort
n=377 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=365 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Total
n=742 Participants
Total of all reporting groups
Age Continuous
36.19 Years
STANDARD_DEVIATION 15.67 • n=5 Participants
38.35 Years
STANDARD_DEVIATION 15.22 • n=7 Participants
37.27 Years
STANDARD_DEVIATION 15.48 • n=5 Participants
Sex: Female, Male
Female
249 Participants
n=5 Participants
232 Participants
n=7 Participants
481 Participants
n=5 Participants
Sex: Female, Male
Male
128 Participants
n=5 Participants
133 Participants
n=7 Participants
261 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 52 Weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

An exacerbation was defined as symptomatic worsening requiring oral/systemic glucocorticoid therapy and/or emergency room visit and/or urgent care center visit and/or hospitalization.

Outcome measures

Outcome measures
Measure
Symbicort
n=377 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=364 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Total Number of Asthma Exacerbations
36 Exacerbations
NA
61 Exacerbations
NA

SECONDARY outcome

Timeframe: 52 Weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Number of participants with at least 1 exacerbation

Outcome measures

Outcome measures
Measure
Symbicort
n=377 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=364 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Asthma Exacerbations
29 Participants
Interval -1.01 to 0.79
51 Participants
Interval -1.23 to 0.61

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

QT interval corrected using the Fridericia formula \[QTc (Frid)\] - Change from baseline to end of treatment

Outcome measures

Outcome measures
Measure
Symbicort
n=377 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=364 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
QT Interval Corrected Using the Fridericia Formula Measured Via Electrocardiogram (ECG)
-0.11 msec
Interval -1.01 to 0.79
-0.31 msec
Interval -1.23 to 0.61

SECONDARY outcome

Timeframe: Baseline and 2 weeks (visit 4)

Population: Data were available for a subset of patients.

Total ectopic ventricular (VE) beats - number of participants with shift from normal (\<50) to high (≥50) from baseline to visit 4.

Outcome measures

Outcome measures
Measure
Symbicort
n=59 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=63 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Number of Patients With Shift From Normal to High Rate of Total Ectopic Ventricular Beats as Measured by 24-hour Holter Monitor Assessment
4 Participants
3 Participants

SECONDARY outcome

Timeframe: Baseline and 2 weeks (visit 4)

Population: Data were available for a subset of patients

Total ectopic supraventricular (VE) beats - number of participants with shift normal (\<50) to high (≥50) from baseline to visit 4.

Outcome measures

Outcome measures
Measure
Symbicort
n=60 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=67 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Number of Patients With Shift From Normal to High Rate of Total Ectopic Supraventricular Beats as Measured by 24-hour Holter Monitor Assessment
4 Participants
3 Participants

SECONDARY outcome

Timeframe: Baseline and 2 weeks (visit 4)

Population: Data were available for a subset of patients.

Total ventricular runs - number of participants with shift normal (\<1) to high (≥1) from baseline to week 2.

Outcome measures

Outcome measures
Measure
Symbicort
n=63 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=74 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Total Number of Ventricular Runs as Measured by 24-hour Holter Monitor Assessment
2 Participants
Interval 13.43 to 18.34
1 Participants
Interval 8.11 to 13.13

SECONDARY outcome

Timeframe: baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Calculated as the number of rescue-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % rescue-free days in the baseline period and the active treatment period. A rescue-free day was one in which the patient answered "no" to having used rescue medication that day

Outcome measures

Outcome measures
Measure
Symbicort
n=369 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=353 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Diary Assessments - Rescue-free Day
15.88 Percentage of Rescue Free Day
Interval 13.43 to 18.34
10.62 Percentage of Rescue Free Day
Interval 8.11 to 13.13

SECONDARY outcome

Timeframe: baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Calculated as the number of symptom-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % symptom-free days in the baseline period and the active treatment period. A symptom-free day was one in which the patient answered "no" to having symptoms that day

Outcome measures

Outcome measures
Measure
Symbicort
n=369 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=353 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Diary Assessments - Symptom-free Day
9.46 percentage of Symptom-free day
Interval 7.55 to 11.37
7.58 percentage of Symptom-free day
Interval 5.62 to 9.53

SECONDARY outcome

Timeframe: baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Calculated as the number of asthma control days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % asthma control days in the baseline period and the active treatment period. An asthma control day was one in which the patient answered "no" to having symptoms and "0" to the use of rescue medication that day

Outcome measures

Outcome measures
Measure
Symbicort
n=369 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=353 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Diary Assessments - Asthma-control Day
16.68 percentage of Asthma-control day
Interval 14.16 to 19.21
11.62 percentage of Asthma-control day
Interval 9.04 to 14.2

SECONDARY outcome

Timeframe: 1 week

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Number of participants with positive response to Item 2 in questionnaire "During the past week,you could feel your study medication begin to work right away. A positive response was defined as a response of "strongly agree" or "somewhat agree"

Outcome measures

Outcome measures
Measure
Symbicort
n=377 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=364 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Onset of Effect Questionnaire (OEQ)
172 Participants
158 Participants

SECONDARY outcome

Timeframe: 1 week

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Number of participants with positive response to Item 5 in questionnaire "During the past week, you were satisfied with how quickly you felt your study medication begin to work." The scale was scored on a 5-point Likert scale from strongly agree to strongly disagree. A positive response was defined as a response of "strongly agree" or "somewhat agree"

Outcome measures

Outcome measures
Measure
Symbicort
n=377 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=364 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Onset of Effect Questionnaire (OEQ)
165 Participants
Interval 46.19 to 49.8
157 Participants
Interval 43.95 to 47.33

SECONDARY outcome

Timeframe: baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Change in AM PEF from baseline (mean over the 2 weeks run-in) to the average of the randomized treatment period.

Outcome measures

Outcome measures
Measure
Symbicort
n=364 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=349 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Peak Expiratory Flow (PEF) in Morning
30.13 Liters/minute
Interval 24.38 to 35.87
19.73 Liters/minute
Interval 13.86 to 25.59

SECONDARY outcome

Timeframe: baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Change in pre-dose FEV1 from baseline (end of run-in, visit 3) to the average of the randomized treatment period

Outcome measures

Outcome measures
Measure
Symbicort
n=359 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=354 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Forced Expiratory Volume in One Second (FEV1)
0.08 Litres
Interval 0.05 to 0.11
-0.01 Litres
Interval -0.04 to 0.01

SECONDARY outcome

Timeframe: Baseline and 52 weeks

Population: The full analysis set, consisting of all randomized patients who received at least one dose of randomized study medication and for whom data were collected after randomization.

Overall score - change from baseline to end of treatment. For 11 individual attributes, expectations were subtracted from the outcomes. This difference and the importance rating were combined in a weighted average which was then multiplied by the raw satisfaction measure. The final derived satisfaction measure was transformed to a 0 to 100 scale, with higher scores representing greater satisfaction.

Outcome measures

Outcome measures
Measure
Symbicort
n=203 Participants
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=232 Participants
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Asthma Treatment Satisfaction Measure (ATSM)
47.99 units on a scale
Interval 46.19 to 49.8
45.64 units on a scale
Interval 43.95 to 47.33

Adverse Events

Symbicort

Serious events: 12 serious events
Other events: 98 other events
Deaths: 0 deaths

Budesonide

Serious events: 15 serious events
Other events: 84 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Symbicort
n=377 participants at risk
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=365 participants at risk
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Gastrointestinal disorders
Oesophageal Fistula
0.00%
0/377
0.27%
1/365
Gastrointestinal disorders
Small Intestinal Obstruction
0.27%
1/377
0.00%
0/365
Infections and infestations
Cellulitis
0.27%
1/377
0.00%
0/365
Infections and infestations
Gastroenteritis
0.27%
1/377
0.00%
0/365
Infections and infestations
Pneumonia
0.00%
0/377
0.27%
1/365
Infections and infestations
Pneumonia Bacterial
0.27%
1/377
0.27%
1/365
Infections and infestations
Subcutaneous Abscess
0.27%
1/377
0.00%
0/365
Injury, poisoning and procedural complications
Ankle Fracture
0.00%
0/377
0.27%
1/365
Injury, poisoning and procedural complications
Foreign Body Trauma
0.00%
0/377
0.27%
1/365
Injury, poisoning and procedural complications
Gun Shot Wound
0.00%
0/377
0.27%
1/365
Injury, poisoning and procedural complications
Hip Fracture
0.27%
1/377
0.00%
0/365
Musculoskeletal and connective tissue disorders
Osteoarthritis
0.53%
2/377
0.00%
0/365
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma
0.53%
2/377
0.00%
0/365
Nervous system disorders
Cerebrovascular Accident
0.27%
1/377
0.00%
0/365
Nervous system disorders
Headache
0.00%
0/377
0.27%
1/365
Nervous system disorders
Migraine
0.00%
0/377
0.27%
1/365
Psychiatric disorders
Anxiety
0.00%
0/377
0.27%
1/365
Psychiatric disorders
Depression
0.00%
0/377
0.27%
1/365
Psychiatric disorders
Schizophrenia
0.00%
0/377
0.27%
1/365
Renal and urinary disorders
Calculus Urinary
0.00%
0/377
0.27%
1/365
Reproductive system and breast disorders
Haemorrhagic Ovarian Cyst
0.27%
1/377
0.00%
0/365
Reproductive system and breast disorders
Ovarian Mass
0.27%
1/377
0.00%
0/365
Respiratory, thoracic and mediastinal disorders
Asthma
0.27%
1/377
1.1%
4/365
Skin and subcutaneous tissue disorders
Angioedema
0.27%
1/377
0.00%
0/365

Other adverse events

Other adverse events
Measure
Symbicort
n=377 participants at risk
Symbicort pMDI 160/4.5 ug x 2 actuations (twice daily) BID
Budesonide
n=365 participants at risk
Budesonide HFA pMDI 160 ug x 2 actuations (twice daily) BID
Infections and infestations
Nasopharyngitis
6.9%
26/377
7.9%
29/365
Infections and infestations
Sinusitis
4.0%
15/377
6.3%
23/365
Infections and infestations
Viral Upper Respiratory Tract Infection
5.8%
22/377
4.4%
16/365
Nervous system disorders
Headache
9.5%
36/377
7.4%
27/365
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
5.0%
19/377
2.5%
9/365

Additional Information

Gerard Lynch

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee The PI may use the Multi-Center Study Results and the Site Data for the limited purpose of his or her own research and academic analysis until the earlier of the publication of the first Multi-Center Study at all participating sites
  • Publication restrictions are in place

Restriction type: OTHER