Efficacy and Safety of Ciclesonide (CIC) administered twice daily in pediatric patients with asthma.

Study identifier:EFC6695

ClinicalTrials.gov identifier:NCT00392288

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A multicenter, multi-national, randomized, double-blind, placebo-controlled, study to assess the efficacy and safety of ciclesonide metered-dose inhaler (MDI) at 80 μg BID or 40 μg BID for 12 weeks in patients aged 4 to <12 years with persistent asthma.

Medical condition

asthma

Phase

Phase 3

Healthy volunteers

Study drug

Ciclesonide, Placebo

Sex

All

Actual Enrollment

528

Study type

Interventional

Age

4 Years - 11 Years

Date

Study Start Date: 01 Sept 2006

Primary Completion Date: 01 Feb 2008

Study Completion Date: 01 Feb 2008

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Sanofi-Aventis Hungaria

Budapest, Hungary

Location

sanofi-aventis Poland

Warszawa, Poland

Location

sanofi-aventis South Africa

Midrand, South Africa

Location

sanofi-aventis, US

Bridgewater, NJ, United States, 08807

Location

sanofi-aventis

Mexico, Mexico

Location

sanofi-aventis administrative office

Moscow, Russian Federation

Arms	Assigned Interventions
Placebo Comparator: Placebo MDI double-blind	Drug: Placebo Placebo MDI over twelve weeks
Experimental: Ciclesonide MDI 40 µg BID double-blind	Drug: Ciclesonide Ciclesonide MDI 40 µg BID over twelve weeks
Experimental: Ciclesonide MDI 80 µg BID double-blind	Drug: Ciclesonide Ciclesonide MDI 80 µg BID over twelve weeks

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Screening period 7-14 days, randomization with subsequent treatment period over 12 weeks

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The number of subjects in section Participant Flow is related to the number of randomized subjects (= subject who were eligible for treatment period). This number is different to the number of subjects of the Intention to Treat (ITT) population in Outcome Measures. The statistical analyses of the Outcome Measures is related to the ITT population.

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Participant Flow: Overall Study

	Placebo metered dose inhaler (MDI)	Ciclesonide MDI 40 µg BID	Ciclesonide MDI 80 µg BID
STARTED	175^[1]	177^[2]	176^[3]
Treatment Period	172	174	175
COMPLETED	143^[4]	155^[5]	159^[6]
NOT COMPLETED	32	22	17
Adverse Event	17	7	8
Lack of Efficacy	8	5	3
Protocol Violation	1	3	1
Lost to Follow-up	1	1	1
Withdrawal by Subject	1	0	2
Parent/legal guardian withdrawal	1	2	1
Unknown	3	4	1

[1]	Number of randomized subjects is different to number of ITT population in Outcome Measures.
[2]	Number of randomized subjects is different to number of ITT population in Outcome Measures.
[3]	Number of randomized subjects is different to number of ITT population in Outcome Measures.
[4]	ITT set = 163 patients
[5]	ITT set = 166 patients
[6]	ITT set = 172 patients

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Baseline Measures

	Placebo metered dose inhaler (MDI)	Ciclesonide MDI 40 µg BID	Ciclesonide MDI 80 µg BID	Total
Number of Participants [units: Participants]	163	166	172	501.0
Age, Customized [units: participants]
Aged 6 to <12 years	136	138	145	419
Aged 4 to <6 years	27	28	27	82
Gender, Male/Female [units: Participants]
Female	59	70	75	204
Male	104	96	97	297

Outcome Measures

1. Primary Outcome Measure: Change from baseline in forced expiratory volume in one second (FEV1) at week 12. [ Time Frame: Baseline and Week 12 ]

Measure Type	Primary
Measure Name	Change from baseline in forced expiratory volume in one second (FEV1) at week 12.
Measure Description	Change in FEV1 (Percent of predicted) from baseline to week 12. FEV1 was measured only in children between 6 to <12 years only. Least Squares Mean were adjusted for Baseline FEV1, age [yrs], pooled center, previous corticosteroid therapy and holding chamber.
Time Frame	Baseline and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analyses are based on children of the ITT population. It includes all randomized patients who have a baseline and a valid post-randomization lung function measurement. The primary analysis was restricted to an age range between 6 and <12 years.

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Measured Values

	Placebo metered dose inhaler (MDI)	Ciclesonide MDI 40 µg BID	Ciclesonide MDI 80 µg BID
Number of Participants Analyzed [units:participants]	136	138	146
Change from baseline in forced expiratory volume in one second (FEV1) at week 12. [units: Percent of predicted FEV1] Least Squares Mean (Standard Error)	5.2 (1.06)	5.3 (1.06)	7.7 (1.06)

Statistical Analysis 1 for Change from baseline in forced expiratory volume in one second (FEV1) at week 12.

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.2696

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	This is an analysis of the change from baseline to week 12 or last visit. In this pairwise comparison Ciclesonide was compared with Placebo by testing the average effect of Ciclesonide 40 and Ciclesonide 80 versus Placebo. As statistical test a t-test was used to compare the corresponding least-square means of both treatment groups.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	ANCOVA model: Change in FEV1 = baseline FEV1 + age [yrs] + treatment + pooled center + previous corticosteroid therapy + holding chamber
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Due to usage of a-priori ordered hypotheses, adjustment of p-values is not necessary. The pre-specified significance level was 0.05. The tests were carried out two-sided.

Statistical Analysis 2 for Change from baseline in forced expiratory volume in one second (FEV1) at week 12.

Groups^[1]	Placebo metered dose inhaler (MDI), Ciclesonide MDI 80 µg BID
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0703

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	This is an analysis of the change from baseline to week 12 or last visit. A t-test was used to compare the least-square means of Ciclesonide 80 versus Placebo.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	ANCOVA model: Change in FEV1 = baseline FEV1 + age [yrs] + treatment + pooled center + previous corticosteroid therapy + holding chamber
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Due to usage of a-priori ordered hypotheses, adjustment of p-values is not necessary. The pre-specified significance level was 0.05. The tests were carried out two-sided.

Statistical Analysis 3 for Change from baseline in forced expiratory volume in one second (FEV1) at week 12.

Groups^[1]	Placebo metered dose inhaler (MDI), Ciclesonide MDI 40 µg BID
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.9146

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	This is an analysis of the change from baseline to week 12 or last visit. As statistical test a t-test was used to compare the corresponding least-square means of Ciclesonide 40 versus Placebo.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	ANCOVA model: Change in FEV1 = baseline FEV1 + age [yrs] + treatment + pooled center + previous corticosteroid therapy + holding chamber
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Due to usage of a-priori ordered hypotheses, adjustment of p-values is not necessary. The pre-specified significance level was 0.05. The tests were carried out two-sided.

2. Secondary Outcome Measure: Change from baseline in total daily asthma symptom score at week 12. [ Time Frame: Baseline and Week 12 ]

Measure Type	Secondary
Measure Name	Change from baseline in total daily asthma symptom score at week 12.
Measure Description	Change in total daily asthma symptom score from baseline to week 12. 5-Point, ordinal scale specifying patient's experience of symptoms during day and night from 0 (no symptoms) to 4 (symptoms that prevent the patient from engaging in daily activities or sleep)
Time Frame	Baseline and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analyses are based on children of the ITT population. It includes all randomized patients who have a baseline and a valid post-randomization lung function measurement.

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Measured Values

	Placebo metered dose inhaler (MDI)	Ciclesonide MDI 40 µg BID	Ciclesonide MDI 80 µg BID
Number of Participants Analyzed [units:participants]	161	165	170
Change from baseline in total daily asthma symptom score at week 12. [units: Scores on a scale] Least Squares Mean (Standard Error)	-0.96 (0.08)	-1.13 (0.08)	-0.99 (0.08)

No statistical analysis provided for Change from baseline in total daily asthma symptom score at week 12.

3. Secondary Outcome Measure: Change from baseline in use of albuterol/salbutamol at week 12. [ Time Frame: Baseline and Week 12 ]

Measure Type	Secondary
Measure Name	Change from baseline in use of albuterol/salbutamol at week 12.
Measure Description	Change in albuterol/salbutamol use from baseline to week 12
Time Frame	Baseline and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analyses are based on children of the ITT population. It includes all randomized patients who have a baseline and a valid post-randomization lung function measurement.

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Measured Values

	Placebo metered dose inhaler (MDI)	Ciclesonide MDI 40 µg BID	Ciclesonide MDI 80 µg BID
Number of Participants Analyzed [units:participants]	162	166	172
Change from baseline in use of albuterol/salbutamol at week 12. [units: Puffs per day] Least Squares Mean (Standard Error)	-0.59 (0.08)	-0.87 (0.08)	-0.93 (0.08)

No statistical analysis provided for Change from baseline in use of albuterol/salbutamol at week 12.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	The numbers of subjects at risk are based on the Safety Population. It was based on all randomized patients receiving at least one dose of the double-blind study medication after randomization.

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Serious Adverse Events

Placebo metered dose inhaler (MDI)

Ciclesonide MDI 40 µg BID

Ciclesonide MDI 80 µg BID

Total, serious adverse events

# participants affected / at risk

1/172 (0.58%)

1/174 (0.57%)

4/175 (2.29%)

Respiratory, thoracic and mediastinal disorders

Asthma¹

# participants affected / at risk

1/172 (0.58%)

0/174 (0.00%)

2/175 (1.14%)

# events

Musculoskeletal and connective tissue disorders

Forearm fracture¹

# participants affected / at risk

0/172 (0.00%)

1/174 (0.57%)

0/175 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Status asthmaticus¹

# participants affected / at risk

0/172 (0.00%)

0/174 (0.00%)

1/175 (0.57%)

# events

General disorders and administration site conditions

Electric shock

# participants affected / at risk

0/172 (0.00%)

0/174 (0.00%)

1/175 (0.57%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	The numbers of subjects at risk are based on the Safety Population. It was based on all randomized patients receiving at least one dose of the double-blind study medication after randomization.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo metered dose inhaler (MDI)	Placebo MDI over twelve weeks (ITT population)
Ciclesonide MDI 40 µg BID	Ciclesonide MDI 40 µg BID over twelve weeks (ITT population)
Ciclesonide MDI 80 µg BID	Ciclesonide MDI 80 µg BID over twelve weeks (ITT population)

Other Adverse Events

Placebo metered dose inhaler (MDI)

Ciclesonide MDI 40 µg BID

Ciclesonide MDI 80 µg BID

Total, other (not including serious) adverse events

# participants affected / at risk

53/172 (30.81%)

38/174 (21.84%)

28/175 (16.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

5/172 (2.91%)

12/174 (6.90%)

8/175 (4.57%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹

# participants affected / at risk

18/172 (10.47%)

10/174 (5.75%)

3/175 (1.71%)

# events

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

9/172 (5.23%)

8/174 (4.60%)

7/175 (4.00%)

# events

Infections and infestations

Upper respiratory tract infection¹

# participants affected / at risk

11/172 (6.40%)

4/174 (2.30%)

10/175 (5.71%)

# events

Infections and infestations

Pharyngitis¹

# participants affected / at risk

17/172 (9.88%)

7/174 (4.02%)

4/175 (2.29%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	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.
	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 more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	AstraZeneca Clinical Study Information Center
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

AstraZeneca AstraZeneca

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Sanofi-Aventis Hungaria

sanofi-aventis Poland

sanofi-aventis South Africa

sanofi-aventis, US

sanofi-aventis

sanofi-aventis administrative office

Trial Results Summaries