Trial Outcomes & Findings for Study Comparing Budesonide Hydrofluoroalkane (HFA) vs Chlorofluorocarbon (CFC) Pressurized Metered Dose Inhalers (pMDI) in Patients With Mild to Moderate Asthma (NCT NCT00667992)

NCT ID: NCT00667992

Last Updated: 2012-11-07

Results Overview

Provocative concentration of methacholine is that causing a 20% fall in FEV1. The methacholine challenge test entailed the patient inhaling from an aerosol containing doubling concentrations of methacholine over a period of 2 minutes until FEV1 had been reduced by 20%. The ratio of Methacholine concentration measured at 2 weeks to that at Baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

99 participants

Primary outcome timeframe

Baseline and week 2

Results posted on

2012-11-07

Participant Flow

144 were enrolled, 45 were excluded: 11 for eligibility not fulfilled, 8 with condition under investigation worsened, 8 for voluntary withdrawal, 17 with reasons not specified, and 1 lost to follow-up and 99 were randomised.

Participant milestones

Participant milestones
Measure
Budesonide Hydrofluoroalkane (HFA) First, Then Budesonide CFC
Budesonide Hydrofluoroalkane (HFA), 100 mcg twice daily followed by Budesonide HFA 400 mcg twice daily First, Wash out, then Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily followed by Budesonide CFC 400 mcg twice daily.
Budesonide Chlorofluorocarbon (CFC) First, Then Budesonide HFA
Budesonide CFC, 100 mcg twice daily followed by Budesonide CFC 400 mcg twice daily First, Wash out, then Budesonide HFA 100 mcg twice daily followed by 400 mcg twice daily.
First Intervention 100 Mcg Twice Daily
STARTED
49
50
First Intervention 100 Mcg Twice Daily
COMPLETED
44
45
First Intervention 100 Mcg Twice Daily
NOT COMPLETED
5
5
Second Intervention 400 Mcg Twice Daily
STARTED
44
45
Second Intervention 400 Mcg Twice Daily
COMPLETED
41
41
Second Intervention 400 Mcg Twice Daily
NOT COMPLETED
3
4
Wash-out
STARTED
41
41
Wash-out
COMPLETED
34
36
Wash-out
NOT COMPLETED
7
5
Third Intervention 100 Mcg Twice Daily
STARTED
34
36
Third Intervention 100 Mcg Twice Daily
COMPLETED
33
35
Third Intervention 100 Mcg Twice Daily
NOT COMPLETED
1
1
Forth Intervention 400 Mcg Twice Daily
STARTED
33
35
Forth Intervention 400 Mcg Twice Daily
COMPLETED
33
35
Forth Intervention 400 Mcg Twice Daily
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Budesonide Hydrofluoroalkane (HFA) First, Then Budesonide CFC
Budesonide Hydrofluoroalkane (HFA), 100 mcg twice daily followed by Budesonide HFA 400 mcg twice daily First, Wash out, then Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily followed by Budesonide CFC 400 mcg twice daily.
Budesonide Chlorofluorocarbon (CFC) First, Then Budesonide HFA
Budesonide CFC, 100 mcg twice daily followed by Budesonide CFC 400 mcg twice daily First, Wash out, then Budesonide HFA 100 mcg twice daily followed by 400 mcg twice daily.
First Intervention 100 Mcg Twice Daily
Condition Under Investigation Worsened
2
3
First Intervention 100 Mcg Twice Daily
Withdrawal by Subject
2
0
First Intervention 100 Mcg Twice Daily
Adverse Event
0
1
First Intervention 100 Mcg Twice Daily
Pregnancy
1
0
Second Intervention 400 Mcg Twice Daily
Withdrawal by Subject
1
0
Second Intervention 400 Mcg Twice Daily
Condition Under Investigation Worsened
2
3
Second Intervention 400 Mcg Twice Daily
Medication not allowed taken
0
1
Wash-out
Not within one doubling dilution
4
3
Wash-out
Failure to wash-out
2
2
Wash-out
Withdrawal by Subject
1
0
Third Intervention 100 Mcg Twice Daily
Withdrawal by Subject
1
0
Third Intervention 100 Mcg Twice Daily
Adverse Event
0
1

Baseline Characteristics

Study Comparing Budesonide Hydrofluoroalkane (HFA) vs Chlorofluorocarbon (CFC) Pressurized Metered Dose Inhalers (pMDI) in Patients With Mild to Moderate Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Budesonide Hydrofluoroalkane (HFA) First, Then Budesonide CFC
n=44 Participants
Budesonide Hydrofluoroalkane (HFA), 100 mcg twice daily followed by Budesonide HFA 400 mcg twice daily, First then Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily followed by Budesonide CFC 400 mcg twice daily.
Budesonide Chlorofluorocarbon (CFC) First, Then Budesonide HFA
n=45 Participants
Budesonide CFC, 100 mcg twice daily followed by Budesonide CFC 400 mcg twice daily First, then Budesonide HFA 100 mcg twice daily followed by 400 mcg twice daily.
Total
n=89 Participants
Total of all reporting groups
Age Continuous
40.0 years
n=5 Participants
39.5 years
n=7 Participants
39.75 years
n=5 Participants
Sex: Female, Male
Female
24 Participants
n=5 Participants
26 Participants
n=7 Participants
50 Participants
n=5 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants
19 Participants
n=7 Participants
39 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 2

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

Provocative concentration of methacholine is that causing a 20% fall in FEV1. The methacholine challenge test entailed the patient inhaling from an aerosol containing doubling concentrations of methacholine over a period of 2 minutes until FEV1 had been reduced by 20%. The ratio of Methacholine concentration measured at 2 weeks to that at Baseline.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
PC 20 Methacholine (Provocative Concentration of Methacholine Causing 20 % Fall in FEV1(Forced Expiratory Volume)
1.546 Ratio
Interval 1.343 to 1.78
2.163 Ratio
Interval 1.877 to 2.494
1.673 Ratio
Interval 1.449 to 1.928
2.079 Ratio
Interval 1.801 to 2.401

SECONDARY outcome

Timeframe: Baseline to week 2 recorded daily

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

Change in PEF at Week 2 from baseline, mean over all days in run-in and all dasy in treatment period, with baseline as covariate.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Peak Exploratory Flow (PEF)
9.7 Liters/minutes
Interval 3.9 to 15.6
12.7 Liters/minutes
Interval 6.8 to 18.6
12.0 Liters/minutes
Interval 6.1 to 17.9
9.1 Liters/minutes
Interval 3.2 to 15.1

SECONDARY outcome

Timeframe: Baseline to week 2

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

FEV1 change from baseline

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
FEV1 (Forced Expiratory Volume in 1 Second)
0.08 Liters
Interval 0.05 to 0.11
0.10 Liters
Interval 0.07 to 0.13
0.10 Liters
Interval 0.07 to 0.13
0.11 Liters
Interval 0.08 to 0.14

SECONDARY outcome

Timeframe: Baseline and week 2

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

FEF 25-75- Forced expiratory flow over the middle one half of the FVC. The results are expressed as the change from baseline

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
FEF 25-75 (Forced Expiratory Flow 25-75)
0.11 Liters/seconds
Interval 0.005 to 0.17
0.14 Liters/seconds
Interval 0.08 to 0.2
0.15 Liters/seconds
Interval 0.09 to 0.21
0.20 Liters/seconds
Interval 0.13 to 0.26

SECONDARY outcome

Timeframe: baseline and week 2

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

eNO ratio of baseline

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
eNO (Exhaled Nitrogen Oxide)
0.66 Ratio
Interval 0.62 to 0.7
0.57 Ratio
Interval 0.53 to 0.6
0.66 Ratio
Interval 0.63 to 0.7
0.59 Ratio
Interval 0.55 to 0.62

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

Asthma Symptom score recorded daily in the morning: Scale: 0-3. 0 = None; no asthma symptoms. 1 = Mild symptoms; aware of asthma symptoms but easily tolerated. 2 = Moderate symptoms; asthma causing enough discomfort to cause problems with normal activities (or with sleep). 3 =Severe symptoms; unable to do normal activities. The average of means for values recorded daily in the morning is presented.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Asthma Symptom Score Morning
0.39 Units on a scale
Interval 0.34 to 0.44
0.29 Units on a scale
Interval 0.24 to 0.34
0.39 Units on a scale
Interval 0.34 to 0.44
0.30 Units on a scale
Interval 0.25 to 0.35

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

Asthma Symptom score recorded daily in the evening: Scale: 0-3. 0 = None; no asthma symptoms. 1 = Mild symptoms; aware of asthma symptoms but easily tolerated. 2 = Moderate symptoms; asthma causing enough discomfort to cause problems with normal activities (or with sleep). 3 =Severe symptoms; unable to do normal activities. The average of means for values recorded daily in the evening is presented.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Asthma Symptom Score Evening
0.48 Units on a scale
Interval 0.43 to 0.52
0.32 Units on a scale
Interval 0.27 to 0.38
0.46 Units on a scale
Interval 0.41 to 0.5
0.36 Units on a scale
Interval 0.31 to 0.41

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

Asthma Symptom score recoded daily, Total. Scale: 0 - 3. 0 = None; no asthma symptoms. 1 = Mild symptoms; aware of asthma symptoms but easily tolerated. 2 = Moderate symptoms; asthma causing enough discomfort to cause problems with normal activities (or with sleep). 3 =Severe symptoms; unable to do normal activities. The average of means for values recorded daily is presented.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Asthma Symptom Score Total
0.87 Units on a scale
Interval 0.78 to 0.96
0.61 Units on a scale
Interval 0.52 to 0.71
0.85 Units on a scale
Interval 0.76 to 0.94
0.66 Units on a scale
Interval 0.56 to 0.76

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

The average of means for inhalations of rescue medication in the morning is presented.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Rescue Medication Morning
0.71 Number of inhalations
Interval 0.6 to 0.82
0.45 Number of inhalations
Interval 0.34 to 0.56
0.62 Number of inhalations
Interval 0.51 to 0.73
0.50 Number of inhalations
Interval 0.39 to 0.61

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

The average of means for inhalations of rescue medication in the evening is presented.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Rescue Medication Evening
0.90 Number of inhalations
Interval 0.77 to 1.03
0.67 Number of inhalations
Interval 0.52 to 0.8
0.84 Number of inhalations
Interval 0.71 to 0.97
0.64 Number of inhalations
Interval 0.5 to 0.78

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

The average of means for inhalations of rescue medication in morning and evening combined over a 24 hour period is presented.

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Rescue Medication Total
1.58 Number of inhalations/24 hours
Interval 1.35 to 1.8
1.10 Number of inhalations/24 hours
Interval 0.86 to 1.33
1.39 Number of inhalations/24 hours
Interval 1.16 to 1.62
1.05 Number of inhalations/24 hours
Interval 0.81 to 1.29

SECONDARY outcome

Timeframe: 2 weeks

Population: Full analysis set (FAS). The FAS was defined as all randomised patients who contributed data from at least one period (ie data from both low and high dose of one inhaler).

Peak Exploratory Flow (PEF) recorded daily in the morning

Outcome measures

Outcome measures
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=80 Participants
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=79 Participants
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon(CFC) 100
n=79 Participants
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=78 Participants
Budesonide CFC 400 mcg twice daily for 2 weeks
Peak Exploratory Flow (PEF) Morning
426 Liters/minutes
Interval 421.0 to 431.0
437 Liters/minutes
Interval 433.0 to 442.0
428 Liters/minutes
Interval 424.0 to 433.0
438 Liters/minutes
Interval 433.0 to 442.0

Adverse Events

Budesonide Hydrofluoroalkane (HFA) 100

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

Budesonide HFA 400

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Budesonide Chlorofluorocarbon (CFC) 100

Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths

Budesonide CFC 400

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

Serious adverse events

Serious adverse events
Measure
Budesonide Hydrofluoroalkane (HFA) 100
n=86 participants at risk
Budesonide Hydrofluoroalkane (HFA) 100 mcg twice daily for 2 weeks
Budesonide HFA 400
n=81 participants at risk
Budesonide HFA 400 mcg twice daily for 2 weeks
Budesonide Chlorofluorocarbon (CFC) 100
n=85 participants at risk
Budesonide Chlorofluorocarbon (CFC) 100 mcg twice daily for 2 weeks
Budesonide CFC 400
n=79 participants at risk
Budesonide CFC 400 mcg twice daily for 2 weeks
Infections and infestations
Oral Candidiasis
0.00%
0/86
1.2%
1/81
0.00%
0/85
0.00%
0/79
Infections and infestations
Lower Respiratory Tract Infection
0.00%
0/86
0.00%
0/81
1.2%
1/85
0.00%
0/79
Infections and infestations
Respiratory Tract Infection Viral
0.00%
0/86
0.00%
0/81
1.2%
1/85
0.00%
0/79

Other adverse events

Adverse event data not reported

Additional Information

Gerard Lynch

AstraZeneca

Results disclosure agreements

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