Clinical Trials Register

Summary
EudraCT Number:	2010-023637-29
Sponsor's Protocol Code Number:	CCD-1012-PR-0051
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-14
Trial results	View 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

Denmark - DHMA

A.2

EudraCT number

2010-023637-29

A.3

Full title of the trial

A SINGLE CENTRE, RANDOMISED, DOUBLE-BLIND, DOUBLE-DUMMY, 2-WAY CROSS OVER STUDY TO COMPARE SAFETY ASSESSED BY KNEMOMETRY AND URINARY CORTISOL MEASUREMENTS OF CHF1535 50/6 pMDI (FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE AND FORMOTEROL FUMARATE) AND THE FREE COMBINATION OF LICENSED BECLOMETHASONE DIPROPIONATE AND FORMOTEROL FUMARATE IN ASTHMATIC CHILDREN ALREADY TREATED WITH INHALED CORTICOSTEROIDS

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Korttidsvækst hos børn med astma og optagelse af beclometason og formoterol
givet i én spray på spacer til børn.

A.4.1

Sponsor's protocol code number

CCD-1012-PR-0051

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/548/2009

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Chiesi Farmaceutici S.p.A.
B.1.3.4	Country	France
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	Chiesi Farmaceutici S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cyncron A/S
B.5.2	Functional name of contact point	Thorbjørn Jensen
B.5.3	Address:
B.5.3.1	Street Address	Teglgården 60
B.5.3.2	Town/ city	Birkerød
B.5.3.3	Post code	3460
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4570202058
B.5.5	Fax number	+4570205677
B.5.6	E-mail	tj@cyncron.com

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	No
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	CHF 1535 50/6microgram pMDI
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	Yes
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	beclomethasone dipropionate
D.3.9.1	CAS number	5534-09-8
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	formoterol fumerate
D.3.9.1	CAS number	43229807
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	6
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Ventolair® in Germany
D.2.1.1.2	Name of the Marketing Authorisation holder	IVAX Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Ventolair®
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
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	beclomethasone dipropionate
D.3.9.1	CAS number	5534-09-8
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	50
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Atimos® 6 μg
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi Farmaceutici S.p.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Atimos® 6 μg,
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
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	formoterol fumerat
D.3.9.1	CAS number	43229807
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	6
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
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	No

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	Inhalation solution
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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

Asthmatic children aged ≥ 5 and < 12 years

E.1.1.1

Medical condition in easily understood language

Asthmatic children aged ≥ 5 and < 12 years

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to show that CHF 1535 50/6µg pMDI, 2 inhalations bid (total daily dose: BDP 200μg / FF 24μg) using AeroChamber Plus™ spacer device is non-inferior to a corresponding free combination of BDP 50μg pMDI, 2 inhalations bid (total daily dose: 200μg) plus FF 6μg pMDI, 2 inhalations bid (total daily dose: 24μg) using AeroChamber Plus™ spacer device in terms of lower leg growth rate (LLGR), measured by knemometry, over a 2-week treatment period

E.2.2

Secondary objectives of the trial

To demonstrate that CHF 1535 50/6 pMDI is non-inferior to a corresponding free combination dose of extrafine BDP 50μg HFA plus Formoterol Fumerate (FF) 6μg in terms of pulmonary function test and safety parameters.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Prepuberal male and female outpatients, ≥ 5 and < 12 years old in Tanner stadium I according to Investigator's assessment;
2. Written informed consent by parents/legal representatives;
3. Clinical diagnosis of mild asthma during at least two months prior to screening visit;
4. Forced Expiratory Volume during the first second (FEV1) > 80% of predicted normal values at screening visit;
5. Treated with inhaled β2-agonists used as rescue medicaton and or beclomethasone up to 400μg daily or equivalent treatments;
6. Compliant to study procedures and able to visit the centre for controls as reported into the protocol. A cooperative attitude and ability to be trained in the proper use of a pMDI and spacers.

E.4

Principal exclusion criteria

1. Male and female out patients in Tanner stadium II-V;
2. Endocrinological diseases including growth impairment or other chronic diseases;
3. Known sensitivity to the components of study medication;
4. Any concomitant disease requiring additional treatment with topic or systemic glucocorticosteroids;
5. Allergy to one component of medications used;
6. Intolerance or contra-indication to treatment with β2-agonists and/or inhaled corticosteroids;
7. Having received an investigational drug within 2 months before the current study;
8. Patient’s participation in another clinical trial in parallel with the present study;
9. Inability to perform outcome measurements optimally and to complete diary cards

E.5 End points

E.5.1

Primary end point(s)

Lower Leg Growth Rate (LLGR) after 2-week treatment with CHF 1535 50/6µg pMDI and free combination of BDP 50μg pMDI plus FF 6μg pMDI will be compared using an ANCOVA model. The model will include treatment and period as fixed effects, subject as a random effect and the baseline LLGR as covariate. Baseline growth rate is the change in lower leg length from beginning to end of run-in period, divided by the time interval between the two measurements.

The difference between treatments for adjusted treatment means will be presented with a two-sided 95% confidence interval. If the lower bound of this interval is greater than or equal to -0.20 mm/week non inferiority will be declared.

E.5.1.1

Timepoint(s) of evaluation of this end point

End of trial

E.5.2

Secondary end point(s)

1) LLGR after each of the two active treatments compared to LLGR at the end of placebo run-in period. An ANOVA analysis with the three treatments (two active treatments and run-in placebo) and subjects as a random effect will be performed. The results of the analysis will be presented with the estimated differences between each of the two treatments and the placebo, with a 95% confidence interval, and a p-value for the treatment difference being equal to 0.
2) The comparison of 24-hour urinary free cortisol/creatinine levels after treatment with CHF 1535 and with free combination of BDP and formoterol will be done using the same model as described in the primary endpoint analysis but without testing for non-inferiority.
Consistently the comparison of 24-hour urinary free cortisol excretion/creatinine after each of the two active treatments with the end of placebo run-in period will be done with the same model used for the LLGR endpoint.
3) Incidence of adverse events (coded with MedDRA) as well as vital signs will be presented by descriptive statistics only.

E.5.2.1

Timepoint(s) of evaluation of this end point

End of trial

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

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

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

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

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

the participants are under age and are not allowed to decide participation themselves. Both parents must consent if the child verbal and bodily agree

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Participants will be treated after trial end as decided by PI. The treatment will not differ from expected normal treatment of asthma in children 5-12 years

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-06-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-29

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