Clinical Trials Register

Summary
EudraCT Number:	2012-005789-36
Sponsor's Protocol Code Number:	FLUI-2012-94
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-29
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-005789-36

A.3

Full title of the trial

Double blind, double dummy, randomized, two way cross-over study to compare the effects of Seretide® Evohaler (supplied by Allen & Hanburys, UK) and a generic test HFA pMDI (manufactured by Cipla Ltd, India) on functional respiratory imaging parameters in asthmatic patients.

Dubbelblinde, dubbel dummy, gerandomiseerde, 2 weg cross-over studie om de effecten van Seretide® Evohaler (geleverd door Allen & Hanburys, UK) en een generieke test HFA pMDI (vervaardigd door Cipla Ltd, India) te vergelijken op functionele respiratoire beeldvorming parameters bij astmapatiënten.

A.3.1

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

Study to compare the effects of Seretide® Evohaler and a generic Seretide variant on respiratory imaging parameters in asthmatic patients.

Studie om de effecten van Seretide® Evohaler en een generieke Seretide variant te vergelijken op respiratoire beeldvorming parameters bij astmapatiënten.

A.4.1

Sponsor's protocol code number

FLUI-2012-94

A.5.4

Other Identifiers

Name:

Study code

Number:

E-RES/12/12-Q13

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	FluidDA nv
B.1.3.4	Country	Belgium
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	FluidDA nv
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FluidDA nv
B.5.2	Functional name of contact point	Jan De Backer
B.5.3	Address:
B.5.3.1	Street Address	Groeningenlei 132
B.5.3.2	Town/ city	Kontich
B.5.3.3	Post code	2550
B.5.3.4	Country	Belgium
B.5.4	Telephone number	3234508720
B.5.5	Fax number	3234508729
B.5.6	E-mail	jan.debacker@fluidda.com

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	Seretide Evohaler 25 microgram /250 microgram/dose pressurised inhalation, suspension
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Wellcome UK Limited Trading as Allen & Hanburys
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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, suspension
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	Fluticasone propionate
D.3.9.1	CAS number	80474-14-2
D.3.9.3	Other descriptive name	FLUTICASONE PROPIONATE
D.3.9.4	EV Substance Code	SUB02241MIG
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	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Salmeterol xinafoate
D.3.9.1	CAS number	94749-08-3
D.3.9.3	Other descriptive name	SALMETEROL XINAFOATE
D.3.9.4	EV Substance Code	SUB04314MIG
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	25
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	Yes
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	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	Salmeterol xinafoate & Fluticasone propionate 25/250 mcg HFA pMDI
D.3.4	Pharmaceutical form	Inhalation powder
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	Fluticasone propionate
D.3.9.1	CAS number	80474-14-2
D.3.9.2	Current sponsor code	Q15E6
D.3.9.3	Other descriptive name	FLUTICASONE PROPIONATE
D.3.9.4	EV Substance Code	SUB02241MIG
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	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Salmeterol xinafoate
D.3.9.1	CAS number	94749-08-3
D.3.9.3	Other descriptive name	SALMETEROL XINAFOATE
D.3.9.4	EV Substance Code	SUB04314MIG
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	25
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	Yes
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

Asthma

Astma

E.1.1.1

Medical condition in easily understood language

Asthma is characterized by episodes of wheezing, breathlessness, chest tightness, coughing. Hypersensitivity to stimuli, narrowing and chronic inflammation of the airways.

Astma wordt gekenmerkt door episodes van piepen, kortademigheid, druk op de borst, hoesten. Overgevoeligheid voor prikkels, vernauwing en een chronische ontstekingsreactie van de luchtwegen.

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	LLT
E.1.2	Classification code	10049106
E.1.2	Term	Asthma chronic
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10003565
E.1.2	Term	Asthmatic
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10003555
E.1.2	Term	Asthma bronchial
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 this study is to evaluate the effect of the products under investigation on Functional respiratory imaging parameters and evaluate the particle deposition with Computational fluid dynamics (CFD).

Het primaire doel van deze studie is om het effect van de onderzoeksproducten te evalueren op parameters bekomen met behulp van functionele respiratoire beeldvorming en de depositie van deeltjes met computationele stromingsdynamica (CFD) te evalueren.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to assess the effect of salmeterol and fluticasone combination therapy on lung function (spirometry and body plethysmography), on exercise capacity (6MWT) and on dyspnea (Borg CR10 Scale and VAS dyspnea). Furthermore the safety of the 2 products under investigation will be evaluated through monitoring of adverse events throughout the study.

De secundaire doelstellingen van dit onderzoek zijn om het effect van salmeterol en fluticason combinatietherapie op de longfunctie (spirometrie en plethysmografie) te beoordelen, op de inspanningscapaciteit (6MWT) en op dyspnoe (Borg CR10 Schaal en VAS dyspnoe). Bovendien zal de veiligheid van de twee onderzochte producten worden geëvalueerd door het opvolgen van bijwerkingen gedurende het onderzoek.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patient ≥ 18 years old
2. Written informed consent obtained
3. Patient with a documented diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines
4. Patient with a co-operative attitude and ability to be trained to correctly use the Seretide® and Cipla Seretide generic MDI
5. Female patient of childbearing potential who confirm that a contraception method was used at least 14 days before visit 1 and will continue to use a contraception method during the study
6. Patient must be stable and treated in accordance with the GINA guidelines
7. Patient must be a non-smoker or ex-smoker who have stopped smoking at least 1 year prior to the visit 1 and has a smoking history of < 10 pack years
8. Patient must be able to understand and complete the protocol requirements, instructions, questionnaires and protocol-stated restrictions

1. Man of vrouw patiënt ≥ 18 jaar oud
2. Geschreven toestemming verkregen
3. Patiënt met een gedocumenteerde diagnose van astma volgens de `Global Initiative for Asthma` (GINA) richtlijnen
4. Patiënt met een coöperatieve houding en in de mogelijkheid tot training correct gebruik van de Seretide ® en Cipla Seretide generieke inhalator
5. Vrouwelijke patiënt in de mogelijkheid om kinderen te krijgen die bevestigt dat een anticonceptie methode werd gebruikt ten minste 14 dagen voor bezoek 1 en blijft een anticonceptie methode te gebruiken gedurende de studie
6. Patiënt moet stabiel zijn en behandeld in overeenstemming met de GINA richtlijnen
7. Patiënt moet een niet-roker of ex-roker zijn die minstens 1 jaar gestopt is met roken voorafgaand aan bezoek 1 en een rookgeschiedenis heeft van <10 pakjaren
8. Patiënt moet in staat zijn om de studie procedures, instructies, vragenlijsten en restricties te begrijpen en na te leven

E.4

Principal exclusion criteria

1. Pregnant or lactating female
2. Unstable patient who developed an exacerbation during the last 8 weeks
3. Patient with upper or lower airways infection
4. Patient unable to carry out pulmonary function testing
5. Patient with an uncontrolled disease or any condition that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study
6. Patient with cancer or any other chronic disease with poor prognosis and /or affecting patient status
7. Patient with allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients
8. Patient unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study
9. Patient who received oral corticosteroids within the last 4 weeks prior to visit 1
10. Patient who received any investigational new drug within the last 4 weeks prior to visit 1 or twice the duration of the biological effect of any drug (whichever is longer).
11. Patient with a history of alcohol or substance abuse that in the opinion of the investigator may be of clinical significance
12. Patient who has undergone major surgery in the last 12 weeks before the visit 1 or has planned to undergo a major surgery before the end of the trial
13. Patient with diagnosis of COPD

1. Zwangere vrouwen of vrouwen die borstvoeding geven
2. Instabiele patiënt die een exacerbatie heeft ontwikkeld tijdens de laatste 8 weken
3. Patiënt met bovenste of onderste luchtwegen infectie
4. Patiënt niet in staat om longfunctietesten uit te voeren
5. Patiënt met een ongecontroleerde ziekte of een aandoening dat de patiënt, naar het oordeel van de onderzoeker, kan blootstellen aan onnodig risico of mogelijks de resultaten of de interpretatie van de studie kan compromitteren
6. Patiënt met kanker of een andere chronische aandoening met een slechte prognose en / of aantasting van de toestand van de patiënt
7. Patiënt met allergie, gevoeligheid of intolerantie voor de onderzoeksmedicatie en / of bestanddelen van de onderzoeksmedicatie
8. Patiënt die zich waarschijnlijk niet kan houden aan het protocol of niet in staat om de aard, omvang en de mogelijke gevolgen van het onderzoek te begrijpen
9. Patiënt die orale corticosteroïden kreeg in de laatste 4 weken voorafgaand aan bezoek 1
10. Patiënt die een experimenteel nieuw geneesmiddel heeft ontvangen in de laatste 4 weken voor bezoek 1 of tweemaal de duur van het biologische effect van een medicijn (als dat langer is).
11. Patiënt met geschiedenis van alcohol of drugsmisbruik, dat naar het oordeel van de onderzoeker van klinische betekenis kan zijn
12. Patiënt die een grote operatie ondergaat in de laatste 12 weken voor bezoek 1 of heeft gepland om een grote operatie te ondergaan voor het einde van de studie
13. Patiënt met diagnose van COPD

E.5 End points

E.5.1

Primary end point(s)

The parameters that will be obtained with Computational fluid dynamics (CFD) and used as primary outcome parameters are:
- Total airway volume and total airway resistance
- The number of deposited particles per pre-defined airway section

De parameters die worden verkregen met computationele stromingsdynamica (CFD) en gebruikt als primaire uitkomstmaten zijn:
- Totaal volume van de luchtwegen en totale weerstand van de luchtwegen
- Het aantal afgezette deeltjes per vooraf gedefinieerde luchtwegen sectie

E.5.1.1

Timepoint(s) of evaluation of this end point

May 2013

Mei 2013

E.5.2

Secondary end point(s)

Secondary outcome variables that will be obtained with respective tests are listed below:
Spirometry/ Lung function :
- Forced Expiratory volume in 1 sec (FEV1),
- Forced Vital Capacity (FVC),
- Peak Expiratory Flow (PEF),
- Maximum Expiratory Flow at 25% of FVC (MEF50),
- Maximum Expiratory Flow at 50% of FVC (MEF25),
- Inspiratory Vital Capacity (IVC),
- Tiffeneau Index (FEV1/FVC ratio)
Bodyplethysmography
- Functional Residual Capacity (FRC),
- Total Lung Capacity (TLC),
- Airway resistance: Airway Resistance (Raw), Specific airway conductance (SGaw)
6 Minute Walk Test
- Exercise capacity: distance walked in 6 minutes (m)
Borg CR10 Scale: measure of the present dyspnea
Visual Analog Scale: measure of the difference in dyspnea before and after treatment

Secundaire uitkomstvariabelen die zullen worden verkregen met respectievelijke testen worden hieronder vermeld:
Spirometrie / Longfunctie:
- Geforceerd expiratoire volume in 1 seconde (FEV1),
- Geforceerde vitale capaciteit (FVC),
- Expiratoire piekstroom (PEF),
- Maximale expiratoire flow bij 25% van de FVC (MEF50),
- Maximale expiratoire flow bij 50% van de FVC (MEF25),
- Inspiratoire vitale capaciteit (IVC),
- Tiffeneau Index (FEV1/FVC ratio)
Bodyplethysmography
- Functionele Residuele Capaciteit (FRC),
- Totale longcapaciteit (TLC)
- Weerstand van de luchtwegen: luchtweg weerstand(Raw), Specifieke luchtwegen geleiding (sGaw)
6 minuten wandeltest
- inspanningscapaciteit: afgelegde afstand in 6 minuten (m)
Borg CR10 Schaal: maat voor de aanwezigheid van dyspnoe
Visuele Analoge Schaal: maat voor het verschil in dyspneu voor en na behandeling

E.5.2.1

Timepoint(s) of evaluation of this end point

May 2013

Mei 2013

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

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

Yes

E.6.13.1

Other scope of the trial description

as comparative trial

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

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

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)

Yes

F.1.3.1

Number of subjects for this age range:

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)

Normal treatment of asthmatic patients

Normale behandeling van astma patiënten

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

2013-02-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-08-08

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