Clinical Trials Register

Summary
EudraCT Number:	2017-000735-14
Sponsor's Protocol Code Number:	L-A/2017/COM/01
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:	2017-10-20
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

2017-000735-14

A.3

Full title of the trial

The efficacy and safety of new formulation of combination of fluticasone propionate / salmeterol (125μg / 25μg) in MDI HFA inhaler compared with the reference drug at a dose of 500μg / 50μg in DPI (dry powder inhaler) type disc in patients with chronic asthma

Skuteczność i bezpieczeństwo nowej formulacji kombinacji propionianu flutikazonu/salmeterolu (125µg/25µg) w inhalatorze MDI HFA w porównaniu z lekiem referencyjnym w dawce 500µg/50µg w inhalatorze suchego proszku (DPI) typu dysk u chorych na przewlekłą astmę oskrzelową

A.3.1

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

A study comparing whether the new drug comprising fluticasone propionate and salmeterol doses of 125μg and 25μg HFA MDI inhaler (spray pressure) applied two puffs twice daily is not less effective than the dose of 500μg / 50μg applied one puff twice daily as powder inhaler (DPI) in patients with asthma

Badanie porównujące czy nowy lek zawierający propionian flutikazonu I salmeterol w dawkach 125µg i 25µg w inhalatorze MDI HFA (aerozol ciśnieniowy) dwa wziewy dwa razy dziennie jest nie mniej skuteczny niż lek referencyjny w dawce 500µg/50µg jeden wziew dwa razy dziennie w inhalatorze proszkowym (DPI) u pacjentów z astmą oskrzelową

A.3.2

Name or abbreviated title of the trial where available

COMBO-Study

A.4.1

Sponsor's protocol code number

L-A/2017/COM/01

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	Lek-Am Sp. z o.o.
B.1.3.4	Country	Poland
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	Lek-Am Sp. z o.o.
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	QAH Sp. z o.o. Sp. k.
B.5.2	Functional name of contact point	Deputy General Manager
B.5.3	Address:
B.5.3.1	Street Address	Zawiszy Czarnego, 10
B.5.3.2	Town/ city	Łódź
B.5.3.3	Post code	91-829
B.5.3.4	Country	Poland
B.5.4	Telephone number	+48426563048
B.5.5	Fax number	+48422911414
B.5.6	E-mail	mateusz.jastrzebski@qah.pl

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	COMBOTEROL fluticasone propionate/salmeterol (125μg / 25μg) in MDI HFA inhaler
D.2.1.1.2	Name of the Marketing Authorisation holder	Przedsiębiorstwo Farmaceutyczne LEK-AM Sp. z o.o.
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SALMETEROL
D.3.9.1	CAS number	89365-50-4
D.3.9.2	Current sponsor code	SALMETEROL
D.3.9.3	Other descriptive name	SALMETEROL
D.3.9.4	EV Substance Code	SUB10430MIG
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.3.8 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	FLUTICASONE
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	125
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	Seretide Disc 500 fluticasone propionate/salmeterol (500μg / 50μg) in DPI device
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Export Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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 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	SALMETEROL
D.3.9.1	CAS number	89365-50-4
D.3.9.2	Current sponsor code	SALMETEROL
D.3.9.3	Other descriptive name	SALMETEROL
D.3.9.4	EV Substance Code	SUB10430MIG
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	FLUTICASONE PROPIONATE
D.3.9.1	CAS number	80474-14-2
D.3.9.2	Current sponsor code	FLUTICASONE PROPIONATE
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	500
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 is a common, chronic respiratory disease affecting 1–18% of the population in different countries. Asthma is characterized by variable symptoms of wheeze, shortness of breath, chest tightness and/or cough, and by variable expiratory airflow limitation. Both symptoms and airflow limitation characteristically vary over time and in intensity. These variations are often triggered by factors such as exercise, allergen or irritant exposure, change in weather, or viral respiratory infections.

Astma to heterogenna choroba, zwykle związana z przewlekłym zapaleniem dróg oddechowych, zdefiniowana przez zespół objawów ze strony układu oddechowego jak świsty, duszności, ucisk w klatce piersiowej i kaszel, zmieniających się w czasie i o różnym nasileniu, którym towarzyszy zmienna obturacja dróg oddechowych

E.1.1.1

Medical condition in easily understood language

Asthma is a common condition that affects the airways. The typical symptoms are wheeze, cough, chest tightness, and shortness of breath. Symptoms can range from mild to severe.

Astma jest przedwlekłą chorobą dróg oddechowych. Typowe objawy to świszczący oddech, kaszel, ucisk w klatce piersiowej i duszność. Objawy mogą się wahać od łagodnych do bardzo ciężkich..

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 prove non-inferiority in terms of efficacy and safety of new formulation of combination of fluticasone propionate / salmeterol (125μg / 25μg) in MDI HFA inhaler applied two puffs twice daily compared with the reference drug at a dose of 500μg / 50μg in DPI (dry powder inhaler) type disc applied one puff twice daily in patients with chronic asthma.
Primary endpoint of the trial: avarage morning PEF during 12-week treatment period (change from Week1 to Week12)

Udowodnić, że w zakresie skuteczności i bezpieczeństwa nowa formulacja kombinacji propionianu flutikazonu/salmeterolu (125µg/25µg) z inhalatora MDI HFA dwa wziewy dwa razy dziennie jest nie gorsza niż lek referencyjny w dawce 500µg/50µg z inhalatora suchego proszku (DPI) typu dysk jeden wziew dwa razy dziennie u chorych na przewlekłą astmę oskrzelową
Pierwszorzędowy punkt końcowy: średnia zmiana porannego PEF podczas 12-tygodniowego okresu leczenia (od wartości wyjściowej — T0 do wartości z 12 tygodnia badania — T12).

E.2.2

Secondary objectives of the trial

Additional endpoints are: asthma control assessment with ACT, quality of life assessment (with mAQLQ test), respiratory capacity, salvation drugs usage, adverse events.

W Badaniu dodatkowo obserwacji podlegać będzie ocena kontroli astmy wg testu ACT, jakości życia mAQLQ, wydolności układu oddechowego (FEV1, FEV1 AUC, FVC, FVC AUC), zużycie leków ratunkowych, liczba zaostrzeń, objawy uboczne.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female, age 18-70
2. Asthma diagnosed min 3 months before the screening visit. Therapy minimal requirement - GINA grade 4
3. FEV1 elevation by at least 12% and min. 200 ml after 400 µg of salbutamol application noted at the screening
4. FEV1 50-85% of predicted at the screening visit.

1. Osoby obojga płci w wieku 18–70 lat
2. Astma oskrzelowa rozpoznana co najmniej 3 miesiące przed pierwszą wizytą. Pacjenci wymagający terapii stopnia co najmniej 4 wg GINA
3. Wzrost FEV1 (forced expiratory volume in one second) o co najmniej 12% i min. 200 ml po podaniu 400 µg salbutamolu wykazany podczas pierwszej wizyty, lub w ostatnim roku przed włączeniem pacjenta do badania
4. Wartość należna FEV1 w zakresie od 50 do 85% na wizycie pierwszej i randomizacyjnej

E.4

Principal exclusion criteria

1. Severe life threatening asthma or hospitalisation due to asthma exacerbation during 3 months before the screening
2. Uncontrolled or untreated significant immunology, endocrinology, hematology, psychiatric, neurology, hepatic, gastrointestinal disorders or neoplasma
3. Heart arythmia or other cardiovascular disorders, including hypertension with DBP ≥ 95 mm Hg
4. Antibiotics taken during last 8 weeks before screening due to respiratory infection
5. Smoking >10 cigarettes/day

1. Ciężka, zagrażająca życiu astma oskrzelowa lub hospitalizacja z powodu zaostrzenia astmy w okresie 3 miesięcy przed pierwszą wizytą
2. Niekontrolowane lub nieleczone klinicznie istotne zaburzenia immunologiczne, hormonalne, hematologiczne, psychiatryczne, neurologiczne, choroby wątroby, nerek i układu pokarmowego oraz nowotwory
3. Obecność lub wywiad w kierunku zaburzeń rytmu serca oraz zdiagnozowane cieżkie choroby układu sercowo-naczyniowego, włączając chorobę wieńcową, niewydolność krążenia i niekontrolowane nadciśnienie tętnicze (ciśnienie rozkurczowe ≥ 95 mm Hg)
4. Infekcja układu oddechowego wymagająca antybiotykoterapii na 8 tygodni przed pierwszą wizytą
5. Palenie więcej niż 10 papierosów na dobę lub ponad 10 paczkolat w wywiadzie

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint of the trial: avarage morning PEF during 12-week treatment period (change from Week1 to Week12)

Pierwszorzędowy punkt końcowy: średnia zmiana porannego PEF podczas 12-tygodniowego okresu leczenia (od wartości wyjściowej — T0 do wartości z 12 tygodnia badania — T12).

E.5.1.1

Timepoint(s) of evaluation of this end point

At the last control visit

Podczas ostatniej wizyty kontrolnej

E.5.2

Secondary end point(s)

Additional endpoints are: asthma control assessment with ACT, quality of life assessment (with mAQLQ test), respiratory capacity, salvation drugs usage, adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study till the last control visit

Podczas całej obserwacji aż do ostatniej wizyty kontrolnej

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

Yes

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)

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

Yes

E.8.1.6

Cross over

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

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

The last visit of the last subject in the trial

Ostatnia kontrolna wizyta ostatniego pacjenta w badaniu.

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:

160

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

220

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)

Routine care.

Rutynowe postępowanie.

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

2018-01-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-02-27

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