Clinical Trials Register

Summary
EudraCT Number:	2012-005350-39
Sponsor's Protocol Code Number:	20122011
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-04-22
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

Netherlands - Competent Authority

A.2

EudraCT number

2012-005350-39

A.3

Full title of the trial

Effects Of extra-fine particle HFA-becLomethasone (HFA-QVAR) Versus course particle treatment In smokers and ex-smokers with Asthma

A.3.1

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

Effects Of extra-fine particle HFA-becLomethasone (HFA-QVAR) Versus course particle treatment In smokers and ex-smokers with Asthma

A.3.2

Name or abbreviated title of the trial where available

Effects of QVAR in smokers and ex-smokers with asthma

A.4.1

Sponsor's protocol code number

20122011

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University Medical Centre Groningen
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	University Medical Center Groningen
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Medical Center Groningen
B.5.2	Functional name of contact point	Maarten van den Berge
B.5.3	Address:
B.5.3.1	Street Address	Hanzeplein 1
B.5.3.2	Town/ city	Groningen
B.5.3.3	Post code	9713GZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31503616161
B.5.6	E-mail	m.van.den.berge@umcg.nl

D. IMP Identification
D.IMP: 1
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	CLENIL® MODULITE® 200 micrograms
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi
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	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
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	Flixotide
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
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	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	QVAR
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA Pharma
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
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

Astma

E.1.1.1

Medical condition in easily understood language

Asthma

Astma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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 compare the efficacy of extra-fine particle HFA-QVAR 200 µg b.i.d. to an equipotent dose of course particle HFA-beclomethasone (HFA-Clenil) 400 µg b.i.d. and with coarse particle HFA-fluticasone (GSK) 250 µg in ex-smokers and smokers with asthma.

Om de werkzaamheid van behandeling met extrafijne deeltjes QVAR twee maal daags 200 µg te vergelijken met grovere deeltjes Clenil twee maal daags 400 microgram en met fluticasone 2 maal daags 250 µg in rokers en ex-rokers met astma.

E.2.2

Secondary objectives of the trial

To compare the provocation test with small particle adenosine with the provocation test that uses AMP.

Om de provocatiest met kleine deeltjes adenosine te vergelijken met de standaard provocatietest waarbij grotere deeltjes adenosine 5'-monofosfaat gebruikt worden.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Males and females with a doctor’s diagnosis of asthma
•Age between 18 and 65 years
•Current- and ex-smokers with ≥ 5 packyears.
•Drop in FEV1 > 20% after provocation with small particle adenosine < 20 mg at visit 1.

•Mannen en vrouwen met een dokter's diagnose astma.
•Leeftijd tussen 18 en 65 jaar.
•Rokers en ex-rokers met 5 of meer packyears
•PD20 kleine deeltjes adenosine < 20 mg.

E.4

Principal exclusion criteria

•An asthma exacerbation during the last 6 weeks or upper respiration tract infection during the last 4 weeks prior to inclusion in the study.
•Severe airway obstruction at baseline, FEV1 < 50% of predicted or < 1.2 liter.
•Physician diagnosed predominant COPD or any other pulmonary disease that could influence the study results as judged by the investigator.
•Pregnant or lactating women.
•Females of childbearing potential without an efficient contraception 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 the use of 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, injectable).
c) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
d) Continuous abstinence.
Periodic abstinence (e.g. calendar, ovulation, symptom-thermal, post-ovulation 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.

•Een astma exacerbatie gedurende 6 weken of een luctweginfectie gedurende 4 weken voor de start van de studie.
•Ernstige luchtwegobstructie bij screening (FEV1 < 50% van de voorspelde waarde of < 1.2 liter.
•De onderzoeksarts schat in dat het ziektebeeld voornamelijk bepaald wordt door COPD.
•Andere aandoeningen die de resultaten van de studie kunnen verstoren in de ogen van de onderzoeker.
•Zwangere vrouwen of vrouwen die borstvoeding geven.
•Geen adequate conceptie. Onder adequate anticonceptie wordt verstaan:
a) Post-menopausal: > 12 maanden spontane amenorrhoe of > 6 maanden amenorrhoe met een serum FSH < 40 mIU / mL.
b) Chirurgische sterilisatie (e.g. bilaterale tuba ligatie, hysterectomy).
b) Hormonale contraception (implantable, patch, oral, injectable).
c) Barrier methode: condoom.
d) Volledige abstinentie.

E.5 End points

E.5.1

Primary end point(s)

•PD20 small particle adenosine.

Co-primary objective (only in case of non-inferiority of QVAR on the primary objective:
•Reduction in peripheral airways resistance (R5-R20) measured with IOS at the provocative dose of small particle adenosine causing the FEV1 to drop with 20% (PD20).

PD20 kleine deeltjes adenosine.

De co-primaire eindpunt (wordt alleen geanalyseerd als QVAR niet inferieur is ten opzichte van Clenil of Fluticasone met betrekking op de PD20 kleine deeltjes adenosine:

vermindering van de perifere luchtwegweerstand (R5-R20) gemeten met IOS op PD20 kleine deeltjes adenosine.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and after each treatment period of two weeks.

Op baseline en na elke behandelperiode van 2 weken.

E.5.2

Secondary end point(s)

•Twice daily symptoms (including night-time symptoms) and peakflow (PEF).
•Resistance (R5, R20, R5-R20) and Reactance at 5 Herz (X5) with IOS.
•Lung function (FEF25, FEF50, FEF75, FEF25-75, PEF, FEV1, FEV1/FVC, FVC/SVC
•Body plethysmography (RV (%predicted), TLC, RV/TLC (%), FRC, FRC/TLC (%), FRC/TLC (%predicted), IC, RV/TLC %predicted).
•Peripheral blood (cell differential counts).
•Delta FVC during PD20 small particle adenosine.
•Questionnaires (Asthma Control Questionnaire (ACQ), Bronchial Hyperresponsiveness Questionnaire (BHQ), and Clinical COPD Questionnaire (CCQ).
•Multiple Breath Washout Analysis: Lung Clearance Index, Sacin and Scond.&
•Genome-wide mRNA and miRNA expression, and DNA methylation in epithelial cells derived from nasal epithelial brushes.

•Twee keer daags symptomen en peakflow.
•Luchtwegweerstand (R5, R20, R5-R20) and Reactance at 5 Herz (X5) gemeten met IOS.
•Longfunctie (FEF25, FEF50, FEF75, FEF25-75, PEF, FEV1, FEV1/FVC, FVC/SVC
•Body plethysmography (RV (%predicted), TLC, RV/TLC (%), FRC, FRC/TLC (%), FRC/TLC (%predicted), IC, RV/TLC %predicted).
•perifeer bloed (celverdeling).
•Delta FVC op PD20 kleine deeltjes adenosine.
•Vragenlijsten (Asthma Control Questionnaire (ACQ), Bronchial Hyperresponsiveness Questionnaire (BHQ), and Clinical COPD Questionnaire (CCQ).
•Multiple Breath Washout Analyse: Lung Clearance Index, Sacin and Scond.&
•Genoom-wijd mRNA and miRNA expressie, and DNA methylation in neusepitheel.

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline and after each treatment period of two weeks.

Op baseline en na elke behandelperiode van 2 weken.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

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

Yes

E.6.11

Pharmacogenomic

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

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

Yes

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 visit of the last subject

Laatste bezoek van de laatste persoon in de studie

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

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.1.2.1

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

F.3.3.1

Women of childbearing potential not using contraception

Information not present in EudraCT

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

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)

None

Geen

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

2013-04-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-19

P. End of Trial
P.	End of Trial Status	Ongoing

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