Clinical Trials Register

Summary
EudraCT Number:	2006-001248-30
Sponsor's Protocol Code Number:	XRP1526B/3031 Ciclesidone
National Competent Authority:	Estonia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-04-18
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Estonia - SAM

A.2

EudraCT number

2006-001248-30

A.3

Full title of the trial

A multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy of ciclesonide metered-dose inhaler at a daily dose of 160 μg administered either in a once-daily in the morning regimen (160 μg qd AM) for 16 weeks or in a 160 μg qd AM regimen for 12 weeks preceded by a twice-daily regimen (80 μg bid) for 4 weeks, or in an 80 μg bid regimen for 16 weeks, in adults and adolescents with mild to moderate persistent asthma not treated with steroids.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

XRP1526B/3031 Ciclesidone

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-Aventis U.S. Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.1.1.1	Trade name	ALVESCO
D.2.1.1.2	Name of the Marketing Authorisation holder	Altana Pharma AG
D.2.1.2	Country which granted the Marketing Authorisation	Estonia
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ciclesonide
D.3.4	Pharmaceutical form	Pressurised inhalation, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ciclesonide
D.3.9.1	CAS number	126544-47-6
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ciclesonide
D.3.9.1	CAS number	126544-47-6
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	inhaled corticostreroid

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Pressurised inhalation, solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness, acute and chronic bronchoconstriction, airway edema, and mucus plugging. The inflammatory component of asthma is thought to involve many cell types including mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells and their biologic products. Subjects with asthma most often present with symptoms of wheezing, shortness of breath, cough, and chest tightness.

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the efficacy, compared to placebo, of ciclesonide at a daily dose of 160 μg administered either in a once-daily in the morning regimen (160 μg qd AM) for 16 weeks or in a 160 μg qd AM regimen for 12 weeks preceded by a twice-daily regimen (80 μg bid) for 4 weeks, or in an 80 μg bid regimen for 16 weeks, in adults and adolescents with mild to moderate persistent asthma not treated with steroids.

E.2.2

Secondary objectives of the trial

To investigate the safety, compared to placebo, of ciclesonide at a daily dose of 160 μg administered either in a 160 μg qd AM regimen for 16 weeks or in a 160 μg qd AM regimen for 12 weeks preceded by an 80 μg bid regimen for 4 weeks, or in an 80 μg bid regimen for 16 weeks, in adults and adolescents with mild to moderate persistent asthma not treated with steroids.

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

Males or females ≥ 12 years of age;
History of persistent bronchial asthma for at least 6 months prior to screening;
Asthma therapy limited to bronchodilators only such as short-acting β2-agonists or methylxanthines for at least one month prior to screening;
At screening and immediately prior to randomization, after an albuterol withhold of at least 6 hours, FEV1 ≥ 60% and ≤ 85% of predicted normal (see Appendix A of the protocol) and have a morning peak expiratory flow of (AM PEF) ≤ 95% of predicted normal (see Appendix B of the protocol);
In subjects using methylxanthines: discontinuation of methylxanthines from at least 24 hours prior to the screening visit onwards;
Evidence during the last 7 days (with non-missing measurements) of the screening period prior to randomization for all of the following signs for lack of asthma control:
− Daytime asthma symptom score >1 (see Section 7.3.1.3 of the protocol) on 3 or more days,
− Albuterol use on 3 or more days,
− AM PEF <80% of predicted normal on 3 or more days;
At screening or immediately prior to randomization, reversibility of FEV1 by at least 12% (relative to the pre-bronchodilator value in liters) after inhalation of 180 μg albuterol (ex-actuator);
FEV1 at randomization within 15% of the FEV1 value (in liters) at screening;
Non-smoker for at least 6 months prior to screening, with less than a 10 pack-year smoking history if previous smoker;
Able to demonstrate acceptable oral inhaler technique with MDI (seeAppendix C of the protocol).

E.4

Principal exclusion criteria

Any use of injectable or oral corticosteroids within 6 months prior to screening;
Any use of an inhaled corticosteroid (ICS) within 30 days prior to screening;
Use of β2-adrenergic blocking agents for any reason;
Upper or lower respiratory tract infection within within 30 days prior to screening;
History of chronic bronchitis, chronic obstructive pulmonary disease, or emphysema;
History of life-threatening asthma, including a history of significant hypercarbia (pCO2 >45 mmHg), prior intubation, respiratory arrest, or seizures as a result of an exacerbation of asthma;
More than 2 in-patient hospitalization or emergency care visits due to asthma exacerbations in the year prior to screening;
Subjects on maintenance immunotherapy who either began their immunotherapy regimen or had a clinically relevant change in their immunotherapy regimen within 30 days prior to screening;
Pregnancy. There are no specific studies of ciclesonide in pregnant women. Therefore pregnant women should be excluded from this study;
• Breast feeding;
• Female subjects of childbearing potential (i.e., ovulating, pre-menopausal, not surgically sterile) unless practicing an adequate method of birth control, or unless sexual abstinence is confirmed at informed consent, or unless premenarchal and prepared to accept counseling on reproductive issues in case of becoming menarchal;
• Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol;
• Treatment with any investigational product within 30 days prior to screening;
• Previous randomization in this study;
• Clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult;
• Any clinically relevant deviation from normal in laboratory parameters that would limit participation in the study or interfere with interpretation of study results;
• History of hypersensitivity to the study drug(s) or to drugs with a similar chemical structure;
ntolerance to albuterol or to excipients in MDI (HFA-134a and ethanol);
History of drug or alcohol abuse;
Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study; Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study;
Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy analysis will be an intention-to-treat (ITT) analysis of covariance (ANCOVA) of the change from baseline to the average of Week 12 (Visit 7) and Week 16 (Visit 8) FEV1 measurements, with factors for treatment, center, and gender, and with baseline FEV1 and age as covariates. In case of discontinuation before Week 16, the following last observation carried forward (LOCF) procedures will be used to determine the endpoint: for subjects who discontinue between Weeks 12 and 16, the average of the Week 12 and the end-of-study measurement will be used, and for subjects who discontinue before Week 12, the end-of-study measurement will be used. The FEV1 measured on Day 1 (Week 0, Visit 3) prior to randomization will be the baseline FEV1 value.
The statistical comparison between the ciclesonide treatment regimens and placebo will be performed in a stepwise fashion to control Type 1 error, in the following order:
1. Ciclesonide 80 μg bid will be compared against placebo at α = 0.05, two-sided. If this test is significant, it can be concluded that ciclesonide 80 μg bid is efficacious, and then proceed to Step 2.
2. The average of the ciclesonide 160 μg qd AM and ciclesonide 80 μg bid —> 160 μg qd AM groups will be compared against placebo at α = 0.05, two-sided. If this test is significant, then proceed to Step 3. This step is included to ensure a closed testing procedure.
3. Compare the ciclesonide 160 μg qd AM group vs. placebo and ciclesonide 80 μg bid —> 160 μg qd AM group vs. placebo, each at α = 0.05, two-sided.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Subjects will be treated with study medication for a total of 16 weeks (consisting of a 12-week maintenance treatment period preceded by a 4-week initial treatment period).
recruitment is competitive. Enrollment into the screening or randomization phase of the study will be stopped when the anticipated or actual subject numbers have been achieved across all study sites.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	Yes
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	Yes
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Information not present in EudraCT
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2006-04-18.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	25
F.4.2	For a multinational trial
F.4.2.1	In the EEA	45
F.4.2.2	In the whole clinical trial	700

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2006-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-05-22

P. End of Trial
P.	End of Trial Status	Completed

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