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

A Phase 3, Randomised, Open-label, Crossover Study to Compare HFA vs CFC pMDI Formulations of Budesonide on Methacholine Hyper-reactivity in Patients With Stable, Persistent, Mild to Moderate Asthma

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00667992

Enrollment

Registered

2008-04-28

Start date

2008-04-30

Completion date

2009-05-31

Last updated

2012-11-07

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

Conditions

Asthma

Keywords

Asthma hyperreactivity

Brief summary

This study is being carried out to see if budesonide with HFA is effective, safe and well tolerated compared with budesonide CFC. Budesonide HFA has been already given in other research studies, in both healthy volunteers and subjects with asthma.

Interventions

DRUGBudesonide HFA

standard daily inhaled dose

DRUGBudesonide CFC

standard daily inhaled dose

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Patients suffering from stable, persistent, mild to moderate asthma as defined by Global Initiative for Asthma (GINA) Guidelines and for whom FEV1 \> 60 % * ICS taking ≤ 1000 μg BDP per day, or equivalent * Methacholine PC20 \< 4 mg/mL

Exclusion criteria

* Known or suspected hypersensitivity to budesonide or any other constituents of the budesonide HFA pMDI or budesonide CFC pMDI. * Currently a smoker or who has ceased smoking within 6 months of Visit 1. * Exacerbations of asthma requiring oral steroids, hospitalisation or change in asthma therapy in the previous three months. * Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) or bronchiectasis

Design outcomes

Primary

Measure	Time frame	Description
PC 20 Methacholine (Provocative Concentration of Methacholine Causing 20 % Fall in FEV1(Forced Expiratory Volume)	Baseline and week 2	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.

Secondary

Measure	Time frame	Description
FEV1 (Forced Expiratory Volume in 1 Second)	Baseline to week 2	FEV1 change from baseline
FEF 25-75 (Forced Expiratory Flow 25-75)	Baseline and week 2	FEF 25-75- Forced expiratory flow over the middle one half of the FVC. The results are expressed as the change from baseline
eNO (Exhaled Nitrogen Oxide)	baseline and week 2	eNO ratio of baseline
Asthma Symptom Score Morning	2 weeks	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.
Asthma Symptom Score Evening	2 weeks	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.
Peak Exploratory Flow (PEF)	Baseline to week 2 recorded daily	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.
Rescue Medication Morning	2 weeks	The average of means for inhalations of rescue medication in the morning is presented.
Rescue Medication Evening	2 weeks	The average of means for inhalations of rescue medication in the evening is presented.
Rescue Medication Total	2 weeks	The average of means for inhalations of rescue medication in morning and evening combined over a 24 hour period is presented.
Peak Exploratory Flow (PEF) Morning	2 weeks	Peak Exploratory Flow (PEF) recorded daily in the morning
Asthma Symptom Score Total	2 weeks	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.

Countries

United Kingdom, United States

Participant flow

Recruitment details

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.

Participants by arm

Arm	Count
Budesonide Hydrofluoroalkane (HFA) First, Then Budesonide CFC 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.	44
Budesonide Chlorofluorocarbon (CFC) First, Then Budesonide HFA 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.	45
Total	89

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Intervention 100 Mcg Twice Daily	Adverse Event	0	1
First Intervention 100 Mcg Twice Daily	Condition Under Investigation Worsened	2	3
First Intervention 100 Mcg Twice Daily	Pregnancy	1	0
First Intervention 100 Mcg Twice Daily	Withdrawal by Subject	2	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
Second Intervention 400 Mcg Twice Daily	Withdrawal by Subject	1	0
Third Intervention 100 Mcg Twice Daily	Adverse Event	0	1
Third Intervention 100 Mcg Twice Daily	Withdrawal by Subject	1	0
Wash-out	Failure to wash-out	2	2
Wash-out	Not within one doubling dilution	4	3
Wash-out	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Budesonide Hydrofluoroalkane (HFA) First, Then Budesonide CFC	Budesonide Chlorofluorocarbon (CFC) First, Then Budesonide HFA	Total
Age Continuous	40.0 years	39.5 years	39.75 years
Sex: Female, Male Female	24 Participants	26 Participants	50 Participants
Sex: Female, Male Male	20 Participants	19 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 86	0 / 81	0 / 85	0 / 79
serious Total, serious adverse events	0 / 86	1 / 81	2 / 85	0 / 79

Outcome results

Primary

PC 20 Methacholine (Provocative Concentration of Methacholine Causing 20 % Fall in FEV1(Forced Expiratory Volume)

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.

Time frame: Baseline and week 2