MIA: Comparing Symbicort® As-Needed or Bricanyl As-Needed or Pulmicort® Once Daily + Bricanyl As-Needed in Asthma Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00989833
• Collaborator: (none)
• Enrollment: 66
• Locations: 10
• Arms: 3
• Duration (Months): 10
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

1. The primary objective of this study is:

• To evaluate the magnitude of the protective effect of the combination of budesonide and formoterol on an as-needed basis compared to the use of terbutaline as-needed on exercise induced bronchoconstriction in adults and adolescents with mild intermittent asthma

1. The secondary objectives of this study are:

• To evaluate the magnitude of the protective effect of the combination of budesonide and formoterol as-needed compared to regular once daily use of budesonide plus terbutaline as-needed on exercise induced bronchoconstriction in adults and adolescents with mild intermittent asthma

• To evaluate safety of budesonide/formoterol as-needed, terbutaline as-needed and regular use of budesonide + terbutaline as-needed as terms of adverse event

Condition or Disease	Intervention/Treatment	Phase
Exercise Induced Asthma	Drug: budesonide; Drug: terbutaline; Drug: budesonide/formoterol	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double Blind, Placebo Controlled, Parallel-group Study With Use of Budesonide/Formoterol "As-needed", or Terbutaline "As-needed" or Regular Use of Budesonide + Terbutaline "As-needed", in Patients With Mild Intermittent Asthma
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A budesonide 400yg + terbutaline 0.4 mg as-needed	Drug: budesonide; 400 yg x 1; Other Names: Pulmicort Turbuhaler ; Drug: terbutaline; 0.4 mg as-needed; Other Names: Bricanyl Turbuhaler
Active Comparator: B placebo + terbutaline 0.4 mg as-needed	Drug: terbutaline; 0.4 mg as-needed; Other Names: Bricanyl Turbuhaler
Active Comparator: C placebo + budesonide/formoterol 160/4.5 yg as-needed	Drug: budesonide/formoterol; 160/4.5 yg as-needed; Other Names: Symbicort Turbuhaler

Outcome Measures

Primary Outcome Measures

1. Percent Change in Maximum Post-exercise Forced Expiratory Volume in One Second (FEV1) Fall After 6 Weeks [Baseline and Visit 6]

   FEV1

Secondary Outcome Measures

1. Percent Change in Maximum Post-exercise FEV1 Fall After 3 Weeks [Baseline and 3 weeks]

   FEV1

2. Bronchial Responsiveness to Mannitol [Baseline and 6 weeks]

   Change in cumulative Mannitol dose in mg in patients with a positive mannitol provocation test at baseline (PD15)

3. Concentration of Exhaled Nitric Oxide [6 weeks]

4. Use of as Needed Medication [6 weeks]

   Mean number of as needed inhalations taken before exercise

5. Asthma Control Measured by a 5-item Asthma Control Questionnaire (ACQ5) [Baseline e and 6 weeks]

   Change in overall ACQ5. ACQ5 measures asthma control and a lower values shows a better asthma control, a higher value is worse. A decrease in the ACQ5 shows an improvement during the treatment period. Range of ACQ5 is 0-5, with 0 as the best value and 5 as the worst value. Further information at www.qoltech.co.uk.

6. Diary Recording of Asthma Symptoms [6 weeks]

   Asthma symptoms during days with exercise

7. Number of Participants With an Adverse Event During the Study [6 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of exercise induced asthma

• Maximum 4 asthmatic episodes per week requiring use of reliever medication

Exclusion Criteria:

• No previous treatment with inhaled oral corticosteroids during the last month before randomisation

• Suspected poor capability to follow instructions, ie to exercise 3-4 times a week

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Oslo		Norway
2	Research Site	Trondheim		Norway
3	Research Site	Goteborg		Sweden
4	Research Site	Huddinge		Sweden
5	Research Site	Linkoping		Sweden
6	Research Site	Lulea		Sweden
7	Research Site	Lund		Sweden
8	Research Site	Skene		Sweden
9	Research Site	Stockholm		Sweden
10	Research Site	Uppsala		Sweden

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Kjell Larsson, Professor, AstraZeneca MC Sweden
• Study Director: Georgios Stratelis, AstraZeneca MC Sweden

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00989833
• Other Study ID Numbers: D5890L00032
• First Posted: Oct 6, 2009
• Last Update Posted: Aug 14, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by AstraZeneca: Exercise induced asthma; Mild intermittent asthma; Exercise induced bronchoconstriction
• Additional relevant MeSH terms: Asthma; Asthma, Exercise-Induced; Budesonide; Terbutaline; Formoterol Fumarate

Study Results

Participant Flow

Recruitment Details	On Visit 1, a total of 189 patients, aged 12-67, were enrolled at 10 study sites in 2 countries: Sweden and Norway. Of 189 enrolled patients, 66 patients were randomized and allocated to study treatment on Visit 3 (7 patients in Norway and 59 patients in Sweden).
Pre-assignment Detail	A standardized exercise test (ECT) with duration of 6 minutes, at approximately 90% of maximal aerobic capacity (as defined on Visit 1) was performed on a treadmill while breathing dry air on Visit 2. Patients with exercised induced bronchoconstriction (defined as fall in FEV1 ≥ 10% ) could be randomized on Visit 3.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Period Title: Overall Study
STARTED	21	22	23
COMPLETED	19	19	21
NOT COMPLETED	2	3	2

Baseline Characteristics

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol	Total
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed	Total of all reporting groups
Overall Participants	21	22	23	66
Age (Count of Participants)
<=18 years	2 9.5%	5 22.7%	5 21.7%	12 18.2%
Between 18 and 65 years	18 85.7%	16 72.7%	18 78.3%	52 78.8%
>=65 years	1 4.8%	1 4.5%	0 0%	2 3%
Sex: Female, Male (Count of Participants)
Female	10 47.6%	6 27.3%	14 60.9%	30 45.5%
Male	11 52.4%	16 72.7%	9 39.1%	36 54.5%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Maximum Post-exercise Forced Expiratory Volume in One Second (FEV1) Fall After 6 Weeks
Description	FEV1
Time Frame	Baseline and Visit 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	20	21	21
Mean (Standard Deviation) [Percent change]	-5.85 (6.50)	0.61 (10.92)	-5.24 (9.64)

2. Secondary Outcome

Title	Percent Change in Maximum Post-exercise FEV1 Fall After 3 Weeks
Description	FEV1
Time Frame	Baseline and 3 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	20	21	21
Mean (Standard Deviation) [Percent change]	-4.07 (5.56)	-1.19 (8.03)	-3.81 (8.68)

3. Secondary Outcome

Title	Bronchial Responsiveness to Mannitol
Description	Change in cumulative Mannitol dose in mg in patients with a positive mannitol provocation test at baseline (PD15)
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	11	6	5
Mean (Standard Deviation) [mg]	67.26 (141.98)	-6.15 (95.10)	151.87 (141.09)

4. Secondary Outcome

Title	Concentration of Exhaled Nitric Oxide
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	19	18	21
Mean (Standard Deviation) [ppb]	25.9 (20.1)	35.5 (36.6)	24.4 (22.4)

5. Secondary Outcome

Title	Use of as Needed Medication
Description	Mean number of as needed inhalations taken before exercise
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	20	20	21
Mean (Standard Deviation) [number of inhalations per day]	0.6 (0.2)	0.8 (0.5)	0.7 (0.5)

6. Secondary Outcome

Title	Asthma Control Measured by a 5-item Asthma Control Questionnaire (ACQ5)
Description	Change in overall ACQ5. ACQ5 measures asthma control and a lower values shows a better asthma control, a higher value is worse. A decrease in the ACQ5 shows an improvement during the treatment period. Range of ACQ5 is 0-5, with 0 as the best value and 5 as the worst value. Further information at www.qoltech.co.uk.
Time Frame	Baseline e and 6 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	20	21	22
Mean (Standard Deviation) [units on a scale]	-0.3 (0.7)	-0.2 (0.8)	-0.4 (0.7)

7. Secondary Outcome

Title	Diary Recording of Asthma Symptoms
Description	Asthma symptoms during days with exercise
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	20	20	21
Mean (Standard Deviation) [Percent of exercise days]	51.1 (30.5)	50.9 (36.6)	49.8 (26.1)

8. Secondary Outcome

Title	Number of Participants With an Adverse Event During the Study
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprises all randomized patients regardless of whether they took IP or not and for whom data had been recorded in the CRF after randomization.

Arm/Group Title	Budesonide/Terbutaline	Terbutaline	Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and terbutaline before exercise and as needed	Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
Measure Participants	21	22	23
Number [Participants]	13 61.9%	13 59.1%	13 56.5%

Adverse Events

Arm/Group Title	Budesonide/Terbutaline		Terbutaline		Budesonide/Formoterol
Arm/Group Description	Budesonide once daily and terbutaline before exercise and as needed		Placebo budesonide once daily and terbutaline before exercise and as needed		Placebo budesonide once daily and budesonide/formoterol before exercise and as needed
All Cause Mortality
	Budesonide/Terbutaline		Terbutaline		Budesonide/Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Budesonide/Terbutaline		Terbutaline		Budesonide/Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/22 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Budesonide/Terbutaline		Terbutaline		Budesonide/Formoterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/21 (33.3%)		10/22 (45.5%)		9/23 (39.1%)
Gastrointestinal disorders
Gastroenteritis	1/21 (4.8%)		0/22 (0%)		3/23 (13%)
General disorders
Headache	1/21 (4.8%)		2/22 (9.1%)		0/23 (0%)
Slight Fever	0/21 (0%)		2/22 (9.1%)		0/23 (0%)
Infections and infestations
Common cold	5/21 (23.8%)		7/22 (31.8%)		5/23 (21.7%)
Injury, poisoning and procedural complications
Fall	0/21 (0%)		0/22 (0%)		2/23 (8.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/21 (0%)		3/22 (13.6%)		1/23 (4.3%)
Sore throat	0/21 (0%)		0/22 (0%)		4/23 (17.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.