Trial Outcomes & Findings for Study to Investigate the Efficacy of Symbicort® SMART. (NCT NCT00839800)

NCT ID: NCT00839800

Last Updated: 2012-11-30

Results Overview

Asthma exacerbation was defined as deterioration in asthma leading to oral glucocorticosteroid \[GCS\] treatment, hospitalization, or emergency room \[ER\] treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2091 participants

Primary outcome timeframe

week 52

Results posted on

2012-11-30

Participant Flow

The first participant entered the study on 16 February 2009, and the last participant completed the study on 23 February 2011. A total of 3209 participants were enrolled at 148 centres in 13 countries in Asia, America and Europe, and 2091 participants who fulfilled the randomisation criteria were randomised.

The study started with an enrolment visit, Visit 1, 1-7 days prior to Visit 2 (run-in). At Visit 2 patients had to have a reversibility of ≥12% relative to baseline and their pre-bronchodilatory Forced expiratory volume in one second (FEV1) had to be ≥50% of the predicted normal value.

Participant milestones

Participant milestones
Measure
Symbicort SMART
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Overall Study
STARTED
1049
1042
Overall Study
COMPLETED
956
932
Overall Study
NOT COMPLETED
93
110

Reasons for withdrawal

Reasons for withdrawal
Measure
Symbicort SMART
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Overall Study
Adverse Event
8
12
Overall Study
Lost to Follow-up
31
26
Overall Study
Withdrawal by Subject
28
34
Overall Study
Incorrect Enrolment
3
3
Overall Study
Study-Specific Discontinuation Criteria
6
13
Overall Study
Safety Reasons
2
1
Overall Study
Other
8
14
Overall Study
Severe Non-Compliance to Protocol
7
7

Baseline Characteristics

Study to Investigate the Efficacy of Symbicort® SMART.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Symbicort SMART
n=1049 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Total
n=2091 Participants
Total of all reporting groups
Age Continuous
45.7 years
n=5 Participants
45.6 years
n=7 Participants
45.7 years
n=5 Participants
Sex: Female, Male
Female
722 Participants
n=5 Participants
692 Participants
n=7 Participants
1414 Participants
n=5 Participants
Sex: Female, Male
Male
327 Participants
n=5 Participants
350 Participants
n=7 Participants
677 Participants
n=5 Participants

PRIMARY outcome

Timeframe: week 52

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

Asthma exacerbation was defined as deterioration in asthma leading to oral glucocorticosteroid \[GCS\] treatment, hospitalization, or emergency room \[ER\] treatment.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1049 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
The Percentage of Participants Who Had Experienced Asthma Exacerbation(s) at the End of the Study
16 percentage of participants
22 percentage of participants

SECONDARY outcome

Timeframe: up to 52 weeks

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

Asthma exacerbation was defined as deterioration in asthma leading to oral GCS treatment, hospitalization, or ER treatment. Number of asthma exacerbations during 52 weeks treatment was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1049 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Number of Asthma Exacerbations
259 Asthma exacerbations
363 Asthma exacerbations

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The mean value from a 52-week treatment period.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1034 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1026 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Morning Peak Expiratory Flow (PEF)
331.8 Liter/minute (L/min)
Standard Deviation 102.2
324.7 Liter/minute (L/min)
Standard Deviation 101.9

SECONDARY outcome

Timeframe: 2-week run-in period (14 - 18 days before randomization - week 0) and a 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The mean value from a 52-week treatment period.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1034 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1026 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Evening PEF
334.2 L/min
Standard Deviation 102.6
327.8 L/min
Standard Deviation 103.1

SECONDARY outcome

Timeframe: 4, 12, 24, 36 and 52 weeks after randomization

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The mean value for Weeks 4, 12, 24, 36 and 52 was analysed.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1049 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Forced Expiratory Volume in One Second (FEV1)
2.258 Liter (L)
Standard Deviation 0.76
2.222 Liter (L)
Standard Deviation 0.77

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The mean value of total daily number of inhalations from the treatment period for use of as-needed medication (daytime, night-time).

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1032 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1026 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Use of As-needed Medication
1.21 inhalations/day
Standard Deviation 1.39
1.46 inhalations/day
Standard Deviation 1.60

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The mean value from the treatment period for Total Asthma Symptom Score (total score: 0 is best - no asthma symptoms; 6 is worst).

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1034 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1025 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Asthma Symptom Score
1.12 units on a scale
Standard Deviation 1.04
1.22 units on a scale
Standard Deviation 1.02

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The mean value from the treatment period was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1024 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1025 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Nights With Awakening(s) Due to Asthma Symptoms
15.7 Nights With Awakening(s)
Standard Deviation 27.1
17.5 Nights With Awakening(s)
Standard Deviation 27.2

SECONDARY outcome

Timeframe: up to 52 weeks

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

Mild asthma exacerbation was defined as morning PEF ≥20% below baseline, daily as-needed medication use ≥2 inhalations above baseline, or a night with awakening due to asthma symptoms. The percentage of participants who had experienced mild asthma exacerbation(s) at the end of the study was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1049 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
The Percentage of Participants Who Had Experienced First Mild Asthma Exacerbations
71 percentage of participants
80 percentage of participants

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

A symptom-free day was defined as a day without daytime or night-time symptoms and without night-time awakenings due to asthma symptoms. The mean value was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1034 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1026 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Symptom-free Days (no Symptoms and no Awakenings)
45.5 symptom-free days
Standard Deviation 37.8
41.6 symptom-free days
Standard Deviation 37.2

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

An as-needed-free day is defined as a night and day with no use of as-needed medication. The mean value from the treatment period was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1032 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1026 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Percentage of As-needed-free Days
51.4 percentage of as-needed-free days
Standard Deviation 36.7
47.2 percentage of as-needed-free days
Standard Deviation 36.7

SECONDARY outcome

Timeframe: 52-week treatment period

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

An asthma-control day was defined as a a night and day with no asthma symptoms, no awakenings due to asthma symptoms, and no as-needed medication use. The mean value from the treatment period was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1033 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1026 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Percentage of Asthma-control Days (no Asthma Symptoms, no Awakenings, and no As-needed Use)
41.7 percentage of asthma-control days
Standard Deviation 37.3
37.9 percentage of asthma-control days
Standard Deviation 36.6

SECONDARY outcome

Timeframe: 4, 12, 24, 36 and 52 weeks after randomization

Population: The analysis set for efficacy was based on the full analysis set (FAS) in line with the ICH E9 guideline.

The ACQ developed by Juniper and colleagues (Juniper et al 1999) was used without the FEV1 and Beta 2-agonist questions. The Asthma Control Questionnaire has 5 questions that are assessed on a 7-point scale from 0 to 6 where 0 represents good control and 6 represents poor control. The overall score is the mean of the five responses. At least 4 out of the 5 questions must have been answered to provide a value. The mean of the overall score for Weeks 4 to 52 was presented here.

Outcome measures

Outcome measures
Measure
Symbicort SMART
n=1040 Participants
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1038 Participants
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Asthma Control Questionnaire (ACQ)
1.162 units on a scale
Standard Deviation 0.78
1.289 units on a scale
Standard Deviation 0.75

Adverse Events

Symbicort SMART

Serious events: 41 serious events
Other events: 279 other events
Deaths: 0 deaths

Symbicort+Terbutaline As Needed

Serious events: 74 serious events
Other events: 293 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Symbicort SMART
n=1049 participants at risk
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 participants at risk
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Cardiac disorders
Acute Myocardial Infarction
0.00%
0/1049
0.10%
1/1042
Cardiac disorders
Angina Pectoris
0.00%
0/1049
0.10%
1/1042
Cardiac disorders
Angina Unstable
0.00%
0/1049
0.10%
1/1042
Cardiac disorders
Coronary Artery Disease
0.00%
0/1049
0.10%
1/1042
Congenital, familial and genetic disorders
Cleft Lip
0.10%
1/1049
0.00%
0/1042
Ear and labyrinth disorders
Meniere's Disease
0.10%
1/1049
0.00%
0/1042
Endocrine disorders
Basedow's Disease
0.00%
0/1049
0.10%
1/1042
Eye disorders
Cataract
0.10%
1/1049
0.10%
1/1042
Eye disorders
Retinal Detachment
0.10%
1/1049
0.00%
0/1042
Gastrointestinal disorders
Abdominal Pain
0.29%
3/1049
0.00%
0/1042
Gastrointestinal disorders
Abdominal Hernia
0.00%
0/1049
0.10%
1/1042
Gastrointestinal disorders
Abdominal Pain Upper
0.00%
0/1049
0.10%
1/1042
Gastrointestinal disorders
Acute Abdomen
0.00%
0/1049
0.10%
1/1042
Gastrointestinal disorders
Anal Fissure
0.00%
0/1049
0.10%
1/1042
Gastrointestinal disorders
Colonic Polyp
0.00%
0/1049
0.10%
1/1042
Gastrointestinal disorders
Diarrhoea
0.00%
0/1049
0.10%
1/1042
Gastrointestinal disorders
Gastric Polyps
0.00%
0/1049
0.10%
1/1042
General disorders
Hernia Obstructive
0.10%
1/1049
0.00%
0/1042
General disorders
Malaise
0.00%
0/1049
0.10%
1/1042
General disorders
Pyrexia
0.00%
0/1049
0.10%
1/1042
Hepatobiliary disorders
Cholelithiasis
0.10%
1/1049
0.00%
0/1042
Hepatobiliary disorders
Hepatotoxicity
0.00%
0/1049
0.10%
1/1042
Immune system disorders
Drug Hypersensitivity
0.00%
0/1049
0.10%
1/1042
Infections and infestations
Pneumonia
0.38%
4/1049
0.19%
2/1042
Infections and infestations
Gastroenteritis
0.10%
1/1049
0.29%
3/1042
Infections and infestations
Tracheobronchitis
0.19%
2/1049
0.00%
0/1042
Infections and infestations
Upper Respiratory Tract Infection Bacterial
0.19%
2/1049
0.00%
0/1042
Infections and infestations
Acute Sinusitis
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Breast Abscess
0.00%
0/1049
0.10%
1/1042
Infections and infestations
Bronchitis
0.00%
0/1049
0.10%
1/1042
Infections and infestations
Bronchopneumonia
0.10%
1/1049
0.00%
0/1042
Infections and infestations
H1n1 Influenza
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Lower Respiratory Tract Infection Bacterial
0.00%
0/1049
0.10%
1/1042
Infections and infestations
Osteomyelitis
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Otitis Media Chronic
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Pneumonia Bacterial
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Septic Shock
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Tooth Abscess
0.00%
0/1049
0.10%
1/1042
Infections and infestations
Urinary Tract Infection
0.10%
1/1049
0.00%
0/1042
Infections and infestations
Varicella
0.00%
0/1049
0.10%
1/1042
Infections and infestations
Viral Infection
0.00%
0/1049
0.10%
1/1042
Injury, poisoning and procedural complications
Traumatic Brain Injury
0.00%
0/1049
0.19%
2/1042
Injury, poisoning and procedural complications
Foot Fracture
0.00%
0/1049
0.10%
1/1042
Injury, poisoning and procedural complications
Joint Injury
0.00%
0/1049
0.10%
1/1042
Injury, poisoning and procedural complications
Lower Limb Fracture
0.00%
0/1049
0.10%
1/1042
Injury, poisoning and procedural complications
Muscle Strain
0.00%
0/1049
0.10%
1/1042
Injury, poisoning and procedural complications
Patella Fracture
0.00%
0/1049
0.10%
1/1042
Injury, poisoning and procedural complications
Sternal Fracture
0.10%
1/1049
0.00%
0/1042
Metabolism and nutrition disorders
Type 2 Diabetes Mellitus
0.00%
0/1049
0.19%
2/1042
Metabolism and nutrition disorders
Diabetes Mellitus
0.00%
0/1049
0.10%
1/1042
Musculoskeletal and connective tissue disorders
Back Pain
0.00%
0/1049
0.10%
1/1042
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
0.00%
0/1049
0.10%
1/1042
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis
0.00%
0/1049
0.10%
1/1042
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma
0.19%
2/1049
0.00%
0/1042
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer In Situ
0.00%
0/1049
0.10%
1/1042
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intestinal Adenocarcinoma
0.00%
0/1049
0.10%
1/1042
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Neoplasm
0.10%
1/1049
0.00%
0/1042
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal Cancer
0.00%
0/1049
0.10%
1/1042
Nervous system disorders
Convulsion
0.00%
0/1049
0.10%
1/1042
Nervous system disorders
Dizziness
0.00%
0/1049
0.10%
1/1042
Nervous system disorders
Syncope
0.00%
0/1049
0.10%
1/1042
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
0.10%
1/1049
0.10%
1/1042
Pregnancy, puerperium and perinatal conditions
Abortion Threatened
0.10%
1/1049
0.00%
0/1042
Pregnancy, puerperium and perinatal conditions
Premature Baby
0.00%
0/1049
0.10%
1/1042
Psychiatric disorders
Major Depression
0.10%
1/1049
0.00%
0/1042
Reproductive system and breast disorders
Breast Calcifications
0.00%
0/1049
0.10%
1/1042
Reproductive system and breast disorders
Dysfunctional Uterine Bleeding
0.00%
0/1049
0.10%
1/1042
Reproductive system and breast disorders
Endometriosis
0.10%
1/1049
0.00%
0/1042
Reproductive system and breast disorders
Infertility Male
0.10%
1/1049
0.00%
0/1042
Respiratory, thoracic and mediastinal disorders
Asthma
0.48%
5/1049
3.0%
31/1042
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.10%
1/1049
0.19%
2/1042
Respiratory, thoracic and mediastinal disorders
Nasal Septum Deviation
0.10%
1/1049
0.00%
0/1042
Skin and subcutaneous tissue disorders
Rash
0.10%
1/1049
0.00%
0/1042
Vascular disorders
Hypertension
0.10%
1/1049
0.10%
1/1042

Other adverse events

Other adverse events
Measure
Symbicort SMART
n=1049 participants at risk
Symbicort Turbuhaler 160/4.5 microgram (mcg) one inhalation twice daily (bid) + Symbicort Turbuhaler 160/4.5 mcg as needed
Symbicort+Terbutaline As Needed
n=1042 participants at risk
Symbicort Turbuhaler 160/4.5 mcg one inhalation twice daily + terbutaline Turbuhaler 0.4 mg as needed
Infections and infestations
Nasopharyngitis
13.1%
137/1049
12.8%
133/1042
Infections and infestations
Bronchitis
6.6%
69/1049
7.4%
77/1042
Infections and infestations
Viral Upper Respiratory Tract Infection
5.7%
60/1049
6.9%
72/1042
Infections and infestations
Pharyngitis
4.7%
49/1049
5.6%
58/1042

Additional Information

Gerard Lynch

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: OTHER