Clinical Trials Register

Summary
EudraCT Number:	2008-000905-12
Sponsor's Protocol Code Number:	CCD-0802-PR-0029
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-05-22
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2008-000905-12

A.3

Full title of the trial

A single dose, randomized, double blind, double dummy, placebo controlled, three-period crossover clinical study, comparing the onset of relief from methacholine induced bronchoconstriction with fixed combination beclomethasone dipropionate 100 μg plus formoterol fumarate 6 μg/actuation pMDI with HFA-134a propellant (Foster®) versus standard salbutamol pMDI 100 μg/actuation (Ventolin® 100 μg) therapy in asthmatic patients

A.3.2

Name or abbreviated title of the trial where available

MART1

A.4.1

Sponsor's protocol code number

CCD-0802-PR-0029

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	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
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	Yes
D.2.1.1.1	Trade name	FOSTER®
D.2.1.1.2	Name of the Marketing Authorisation holder	CHIESI FARMACEUTICI SpA
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	Foster®
D.3.2	Product code	CHF 1535 HFA
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	beclomethasone dipropionate
D.3.9.1	CAS number	5534098
D.3.9.3	Other descriptive name	BDP
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.3.8	INN - Proposed INN	Formoterol fumarate
D.3.9.1	CAS number	43229807
D.3.9.3	Other descriptive name	FF
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)	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	No
D.3.11.8	Extractive medicinal product	No
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	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	Ventolin® 100μg
D.2.1.1.2	Name of the Marketing Authorisation holder	GLAXOSMITHKLINE SpA
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	Ventolin® 100μg
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	Salbutamol
D.3.9.1	CAS number	35763-26-9
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)	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	No
D.3.11.8	Extractive medicinal product	No
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	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	Pressurised 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	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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma

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 compare the onset of relief from methacholine-induced bronchospasm with a single dose of Foster® 100/6 versus standard salbutamol pMDI 100 μg/dose therapy, in terms of pulmonary function [time to recovery in FEV1 (return to 85% of baseline)] in asthmatic patients on low-medium doses of ICS (Inhaled corticosteroid).

E.2.2

Secondary objectives of the trial

To evaluate the effect of the treatments on additional lung function parameters and clinical outcome measures of Foster® 100/6.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject’s written informed consent.
2. Outpatients of both sexes aged ≥ 18 years.
3. Diagnosis of asthma for a minimum of 6 months prior to Visit 1.
The evidence of asthma must be confirmed through a documented positive response to the reversibility test, defined as ΔFEV1 ≥ 12% and ≥ 200 mL over baseline, within 30 minutes after administration of 400 μg of salbutamol pMDI or through a positive response to methacholine challenge test (PC20 < 8 mg/mL or PD20 < 1 mg). In
case this is not achieved, a positive historically documented FEV1 reversibility or response to methacholine challenge test within the previous 6 months is acceptable for the diagnosis of asthma. The investigator, according to his/her clinical judgment, will decide about performing the reversibility test or the methacholine challenge test.
4. Baseline FEV1 > 70% of the predicted normal value and at least 1.5 L, after appropriate washout from bronchodilators.
5. Patients on previous treatment with low-medium doses of ICS (200 - 1000 μg BDP CFC daily or equivalent) or ICS + LABA fixed or free combinations (daily dose of budesonide 200 - 800 μg/fluticasone 100 - 500 μg or equivalent ICS doses plus
formoterol 12 - 24 μg of salmeterol 50 - 100 μg) at a stable dose for at least 2 months prior to inclusion. The fixed combination therapies must be switched to the free components ICS alone at the same dose + LABA alone at the same dose in order to stop LABA only 48 hours before each clinic visit.
6. A cooperative attitude and ability to be trained about the proper use of a pMDI.

E.4

Principal exclusion criteria

1. Patients with other lung diseases such as (but not limited to) COPD (Chronic Obstructive Pulmonary Disease), cystic fibrosis, interstitial lung diseases or any other clinically or functionally significant lung disorder.
2. Patients who experienced an acute bronchoconstriction induced by methacholine that, according to the investigator’s opinion, could not be easily managed through SABAs.
3. Patients having received an investigational drug within 2 months.
4. Patients having suffered from a heart attack or stroke within the previous 3 months.
5. Patients with a known aortic or cerebral aneurysm.
6. Patients suffering from uncontrolled hypertension (systolic pressure > 200 and/or diastolic pressure > 110 mmHg).
7. Patients who suffer from uncontrolled cardiovascular, respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other diseases, as well as any condition that might, in the judgement of the investigator, represent for the patients an undue risk or that could compromise the results or the interpretation of the study.
8. Clinically relevant laboratory abnormalities such as (but not limited to) hypokaliemia, that might compromise patient’s safety or compliance, interfere with evaluation, or preclude completion of the study, in the judgment of the investigator.
9. Patients with uncontrolled diabetes including patients with a history of blood glucose levels consistently out of the normal range or HbA1C > 8.0% measured at V1.
10. Patients who have an abnormal QTC interval value in the screening visit ECG test (i.e., > 450 msec in males or > 470 msec in females).
11. Use of systemic steroids within 6 weeks prior to Visit 1.
12. Intolerance/hypersensitivity or contra-indication to treatment with β2-agonists and/or inhaled steroids.
13. Any change in dose, schedule, formulation or product of previous ICS or fixed/free combination ICS + LABA in the 2 months prior to screening visit.
14. Moderate/severe exacerbation and/or intake of oral corticosteroids during the run-in period.
15. Patients treated with slow-release corticosteroids in the 3 months prior to screening visit.
16. Patients being treated with anti-IgE antibodies.
17. Latest moderate/severe asthma exacerbation within 6 weeks.
18. Inability to comply with study procedures or with study treatment intake.
19. Significant response to the diluents, (i.e., > 15% fall in FEV1 from the patient’s FEV1 at baseline, prior to commencing the methacholine challenge test).
20. Upper or lower respiratory tract infection within the previous 6 weeks.
21. History of near fatal asthma.
22. Any acute or clinical condition that put the patient at risk or may alter the interpretation of the test.
23. Pregnant or lactating women. Females of childbearing potential without an efficient contraception. Pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chronic gonadotrophin laboratory test (> 5 mIU/mL). Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or are using one or more of the following acceptable methods of contraception:
a) surgical sterilization (e.g., bilateral tubal ligation, hysterectomy);
b) hormonal contraception (implantable, patch, oral);
c) double-barrier methods (any double combination of: IUD, male
or female condom, diaphragm, sponge, cervical cap).
Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.
24. Use of coffee, tea, cola drinks, chocolate, or other foods containing caffeine 8 hours before the challenge test.
25. Strenuous exercise in the last 2 hours before the challenge.
26. Previous or current smokers who have a smoking history greater that 5 pack years. Current smoking for 1 hour before the challenge test.
27. Patients having received a live-attenuated virus vaccination within 2 weeks prior to screening or during the run-in period.
28. Major surgery in the previous 3 months.

E.5 End points

E.5.1

Primary end point(s)

Time to recovery in FEV1 (return to 85% of the baseline).

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)

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

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.8.3

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

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

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.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)

Subjects will return to the care of their General Practitioner, and will resume treatment as before participation in the trial.

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

2009-06-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-08-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-11-09

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials