Clinical Trials Register

Summary
EudraCT Number:	2011-005108-14
Sponsor's Protocol Code Number:	CCD-1104-PR-0062
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-20
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2011-005108-14

A.3

Full title of the trial

A single- dose, open label, randomized, 3-way crossover, clinical pharmacology study of CHF 1535 100/6 pMDI (fixed combination of beclomethazone dipropionate 100 μg plus formoterol fumarate 6 μg) with or without spacer device versus the free combination of licensed beclomethasone pMDI and formoterol pMDI in asthmatic adolescent patients and one open arm for adult patients as control group treated with CHF 1535 100/6 pMDI.

A.3.1

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

Clinical study to test that the drug CHF 1535 100/6 (fixed combination of an anti-inflammatory drug and relaxing airways drug) delivered via pressurized inhaler using or not a spacer device is as effective in adolescent population as the licensed free combination of the same substances and compare it with administration in adults.

A.4.1

Sponsor's protocol code number

CCD-1104-PR-0062

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/192/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Chiesi Farmaceutici S.p.A.
B.1.3.4	Country	Italy
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	Chiesi Farmaceutici S.p.A.
B.5.2	Functional name of contact point	Chiesi Farmaceutici S.p.A.
B.5.3	Address:
B.5.3.1	Street Address	Via Palermo 26/A
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43122
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390521 2791
B.5.6	E-mail	g.lucci@chiesi.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	Yes
D.2.1.1.1	Trade name	Foster®
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.3.4	Pharmaceutical form	Pressurised 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	BECLOMETASONE DIPROPIONATE
D.3.9.1	CAS number	5534-09-08
D.3.9.4	EV Substance Code	SUB00681MIG
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	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	43229-80-7
D.3.9.3	Other descriptive name	FORMOTEROL FUMARATE
D.3.9.4	EV Substance Code	SUB02257MIG
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	Atimos®
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.3.4	Pharmaceutical form	Pressurised 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.3.9.1	CAS number	43229-80-7
D.3.9.3	Other descriptive name	FORMOTEROL FUMARATE
D.3.9.4	EV Substance Code	SUB02257MIG
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: 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	Qvar®
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Pressurised 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	BECLOMETASONE DIPROPIONATE
D.3.9.1	CAS number	5534/09/08
D.3.9.4	EV Substance Code	SUB00681MIG
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	100
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma

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	14.1
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

To evaluate, in adolescents, the systemic exposure to B17MP (active metabolite of BDP) as
AUC0-t, after inhalation of CHF 1535 100/6 pMDI with and without spacer device (AeroChamber
Plus™) in comparison with the already licensed free combination of BDP pMDI and formoterol
pMDI without spacer.

E.2.2

Secondary objectives of the trial

- To evaluate the pharmacokinetic profile of BDP and formoterol and additional PK
properties of B17MP after inhalation of CHF 1535 100/6 pMDI both with and without
spacer in comparison with a free combination of licensed BDP and Formoterol pMDIs.
- To evaluate the systemic effects in terms of heart rate and circulating potassium and glucose
levels and also the general safety and tolerability profile of BDP/B17MP and formoterol of
CHF 1535 100/6 pMDI fixed combination both with and without spacer.
- To evaluate, in adolescents, the effects of the spacer device (AeroChamber Plus™) on the
systemic exposure to BDP/B17MP and formoterol after inhalation of the fixed combination.
- To evaluate the systemic exposure to BDP/B17MP and formoterol after inhalation of CHF
1535 pMDI in adolescents in comparison to adults without the spacer device.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female adolescents, aged ≥ 12 and < 18 years or male and female adults, aged ≥ 18
and ≤ 65 years.
2. Written informed consent obtained by the patient in case of adult patients and by parents/legal
representative and by the minor (according to local regulation).
3. A diagnosis of asthma as defined in the GINA guidelines (updated 2010) 6 months before the
screening visit.
4. Male/female adolescent and adult patients with asthma stable enough, according to GINA
guidelines (updated 2010) and based on the Investigator’s opinion, to allow a wash out period
from inhaled BDP of 2 days before study each single day study treatments and any ICS other
than BDP of 1 day before each single day study treatments.
5. Male/female adolescents and adults asthmatic patients already treated with ICS or ICS/longacting
inhaled β2-agonists or using short-acting inhaled β2-agonists as reliever to control
asthma symptoms.
6. Adolescents and adults with a forced expiratory volume in one second (FEV1) > 70% of
predicted values (% pred) after withholding short acting β2-agonist treatment for a minimum of
6 h prior to screening or 24 hours in case of long acting β2-agonist.
7. Non- or ex-smokers who smoked less than 5 pack-years (e.g. < 20 cigarettes per day for 5 years)
and stopped smoking for at least 1 year.
8. A cooperative attitude and ability to be trained about the proper use of pMDI with and without
a spacer device and compliant to study procedures.
9. Body mass index (BMI) ≥18.5 and ≤ 32 kg/m2

E.4

Principal exclusion criteria

1. Pregnant or breast-feeding female patients. Sexually active female not using efficient
contraception throughout the entire study period (e.g. oestro-progestatives, condoms,
intrauterine devices). A urinary pregnancy test will be performed at screening and treatment
visits (mandatory in the adult population and at discretion of the investigator in the adolescent
population) in women of childbearing potential;
2. Having received an investigational drug within 2 months before the screening visit (Visit 1)
3. Diagnosis of COPD, in the adult patients, as defined by the current GOLD guidelines (updated
2010).
4. Known hypersensitivity to the active treatments.
5. Inability to perform the required breathing technique and blood sampling.
6. Hospitalization due to exacerbation of asthma within 1 month prior to screening visit.
7. Lower respiratory tract infection within 1 month prior to screening visit;
8. Obesity, i.e. > 97% weight percentile by local standards.
9. Significant medical history of and/or treatments for cardiac, renal, neurological, hepatic,
endocrine diseases, that may interfere with patient’s safety, compliance, or study evaluations,
according to the Investigator’s opinion;
10. History of drug addiction or excessive use of alcohol (weekly intake in excess of 28 units
alcohol; one unit being a glass of beer, wine or a measure of spirits), or excessive consumption
of xanthine containing substances (daily intake in excess of 5 cups of coffee, tea, cola, etc) or
psychological or other emotional problems likely to invalidate informed consent, or limit the
ability of the subject to comply with the protocol requirements;
11. Treatment with a xanthine derivative (e.g. theophylline) formulations in the 4 weeks prior to
screening visit;
12. Blood donation (450 mL or more) (for the adult population) or significant blood loss in the 12
weeks before the screening visit.

E.5 End points

E.5.1

Primary end point(s)

Plasma AUC0-t for B17MP

E.5.1.1

Timepoint(s) of evaluation of this end point

The area under the plasma concentration vs. time curve observed from time 0 up to the last
measurable concentration will be computed using the linear trapezoidal rule [13]. An 8 hour value is required for derivation of AUC0-t.
Nine (9) blood samples of approximately 1 mL for the determination of BDP and its metabolite B17MP in plasma will be collected in the 0-8 h interval after dosing [pre-dose (within 5 minutes from dosing), 5 min, 15 min, 30 min, 1, 2, 4, 6, 8 hours post dose].

E.5.2

Secondary end point(s)

Pharmacokinetics:
- Plasma BDP and formoterol AUC0-t, AUC0-inf , Cmax, tmax and t½
- Plasma B17MP AUC0-0.5h, AUC0-inf, Cmax, tmax and t½
Pharmacodynamics:
- Plasma Potassium Cmin, tmin and AUC0-t
- Plasma Glucose Cmax, tmax, AUC0-2h and AUC0-t
Efficacy:
- Peak FEV1, FEV1 time averaged value (FEV1 AUC0-8h/8h)
Safety:
- Heart Rate: Time averaged value (calculated as AUC0-8h/8h).
- General tolerability of the treatments, adverse events and adverse drug reactions.

E.5.2.1

Timepoint(s) of evaluation of this end point

PK - BDP/B17Mp/Formoterol in plasma at pre-dose, 5 min, 15 min, 30 min, 1, 2, 4, 6, 8 hours post dose
PD - Potassium and Glucose at pre-dose, 30 min, 1, 2, 4, 6, 8 hours post dose;
Safety - Heart rate will be measured at pre-dose, 5 min, 10 min, 15 min, 30 min, 1, 2, 4, 6, 8 hours post dose
Efficacy - Lung function measurements (FEV1) at pre-dose, 30 min, 1, 2, 4, 6, 8 hours post dose

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

last patient Follow-Up.

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

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)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

At study completion, it is under the Investigator’s responsibility to prescribe the most appropriate
treatment for the patient or restore the initial therapy.

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

2012-01-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-08-24

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